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diff --git a/old/64268-0.txt b/old/64268-0.txt deleted file mode 100644 index 2e33480..0000000 --- a/old/64268-0.txt +++ /dev/null @@ -1,6749 +0,0 @@ -The Project Gutenberg eBook of Blood Transfusion, by Geoffrey Keynes - -This eBook is for the use of anyone anywhere in the United States and -most other parts of the world at no cost and with almost no restrictions -whatsoever. You may copy it, give it away or re-use it under the terms -of the Project Gutenberg License included with this eBook or online at -www.gutenberg.org. If you are not located in the United States, you -will have to check the laws of the country where you are located before -using this eBook. - -Title: Blood Transfusion - -Author: Geoffrey Keynes - -Release Date: January 11, 2021 [eBook #64268] - -Language: English - -Character set encoding: UTF-8 - -Image source(s): https://archive.org/details/bloodtransfusion00keynuoft - -Produced by: deaurider, John Campbell and the Online Distributed - Proofreading Team at https://www.pgdp.net (This file was - produced from images generously made available by The Internet - Archive) - -*** START OF THE PROJECT GUTENBERG EBOOK BLOOD TRANSFUSION *** - - - - - TRANSCRIBER’S NOTE - - Italic text is denoted by _underscores_. - - Bold text is denoted by =equal signs=. - - Footnote anchors are denoted by [number], and the footnotes have - been placed at the end of the book. - - Bibliography references are denoted by (number), and the list can - be found near the end of the book. - - A superscript is denoted by ^x or ^{xx}, for example 4^o. - - A subscript is denoted by _{x}, for example C_{6}H_{5}NO_{2}. - - Basic fractions are displayed as ½ ⅓ ¼ etc; other fractions are - shown in the form a/b, for example 1/13 or 1/10·5. - - Obvious typographical errors and punctuation errors have been - corrected after careful comparison with other occurrences within - the text and consultation of external sources. No other changes - to the text have been made. - - - - -BLOOD TRANSFUSION - - - - - OXFORD MEDICAL PUBLICATIONS - - BLOOD TRANSFUSION - - BY - GEOFFREY KEYNES - M.A., M.D. CANTAB., F.R.C.S. ENG. - SECOND ASSISTANT, SURGICAL PROFESSORIAL UNIT - ST. BARTHOLOMEW’S HOSPITAL - - - LONDON - HENRY FROWDE _AND_ HODDER & STOUGHTON - THE _LANCET_ BUILDING - 1 BEDFORD STREET, STRAND, W.C.2 - - - - - _First published in 1922_ - - - PRINTED IN GREAT BRITAIN - BY HAZELL, WATSON AND VINEY, LD., - LONDON AND AYLESBURY. - - - - -PREFACE - - -Blood transfusion is of rapidly growing importance in modern -therapeutics, yet the subject has only been represented in -the medical literature of this country hitherto by isolated -communications concerning special points. The present work seeks to -give a connected account of the whole subject and of the problems -arising from it, together with practical instructions for performing -transfusions by an efficient and simple method. - -I am indebted for helpful criticisms and suggestions to Professor A. -V. Hill, F.R.S., of Manchester University. Dr. J. H. Drysdale has -kindly allowed me to use the records of three cases of pernicious -anæmia treated in his wards at St. Bartholomew’s Hospital. Dr. Joekes -has permitted me to refer to some of his own observations concerning -abnormal serum reactions. Dr. R. M. Janes has given me some account -of the important work recently done by Dr. Bruce Robertson and -himself at the Hospital for Sick Children, Toronto. - -The Bibliography at the end of the book makes no pretence of being -absolutely complete. It is, however, more extensive than any that has -yet been printed, and I believe that it contains references to nearly -all the contributions of present importance published up to the date -of going to press. Numbers referring to the Bibliography have been -inserted in the text only where no name is given to the authority -quoted. - - GEOFFREY KEYNES. - - 86, HARLEY STREET, W.1. - _February 1922_. - - - - - CONTENTS - - - CHAPTER I - PAGE - HISTORICAL SKETCH 1 - - - CHAPTER II - - INDICATIONS FOR BLOOD TRANSFUSION: HÆMORRHAGE - AND SHOCK 19 - - - CHAPTER III - - INDICATIONS FOR BLOOD TRANSFUSION--_continued_: - HÆMORRHAGIC DISEASES--BLOOD DISEASES--TOXÆMIAS 44 - - - CHAPTER IV - - DANGERS OF BLOOD TRANSFUSION 67 - - - CHAPTER V - - PHYSIOLOGY AND PATHOLOGY OF BLOOD GROUPS 79 - - - CHAPTER VI - - THE CHOICE OF BLOOD DONOR 97 - - - CHAPTER VII - - THE METHODS OF BLOOD TRANSFUSION 108 - - BIBLIOGRAPHY 137 - - INDEX 159 - - - - -BLOOD TRANSFUSION - - - - -CHAPTER I - -HISTORICAL SKETCH - - -From the earliest times the vital importance of blood to the human -system has been fully appreciated. It has been supposed to carry -in it some of the virtues, such as the youth and health, of its -possessor, and it has therefore been commonly regarded as a sacrifice -acceptable to the gods. References to blood in the Old Testament, in -classical authors, and, it is stated, in the writings of the ancient -Egyptians, refer rather to these mystical attributes than to any -definite transference of it from the veins of one animal to those -of another. One of the earliest references to actual transfusion of -blood that has been noticed is to be found in a work by Libavius of -Halle, published in 1615. The passage has been translated as follows: - -“Let there be present a robust healthy youth full of lively blood. -Let there come one exhausted in strength, weak, enervated, scarcely -breathing. Let the master of the art have little tubes that can be -adapted one to the other; then let him open an artery of the healthy -one, insert the tube and secure it. Next let him incise the artery of -the patient and put into it the feminine tube. Now let him adapt the -two tubes to each other and the arterial blood of the healthy one, -warm and full of spirit, will leap into the sick one, and immediately -will bring him to the fountain of life, and will drive away all -languor.” - -It may be assumed, however, that this was only an idea, and had -not yet been carried into practice. It was, indeed, unlikely that -any attempt to perform blood transfusion would be made until the -conception of the circulation of the blood had been promulgated, and -this in 1615 had not yet taken place. - -William Harvey had been appointed physician to St. Bartholomew’s -Hospital in 1609, and already in 1616 as Lumleian lecturer had stated -his theory of the circulation, but not until its publication twelve -years later could it be generally known. His treatise entitled -_Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus_, -which appeared in 1628, may therefore be regarded as the point from -which blood transfusion first arose. It has often been stated in the -literature of the subject that the first transfusion was performed -in 1492, when the blood of three boys is supposed to have been -transfused into the veins of the aged Pope Innocent VIII.[1] This, -however, seems to have been a mis-statement of the facts. Actually a -Jewish physician prepared a draught for the Pope from the blood of -three boys, who were bled to death for the purpose.[2] The drinking -of blood was not a new idea; this particular incident is of no -special interest, and may now be allowed to sink into oblivion. - -It is not until after the middle of the seventeenth century that -authentic references to blood transfusion are to be found. The first -is in the writings of Francesco Folli, a Florentine physician, who -claims to have demonstrated the operation of transfusion of blood on -August 13, 1654, to the Grand Duke Frederick II. There does not seem -to be any confirmation of this in the writings of others. A few years -later experimental work tending in the same direction was being done -in England, and the inception of this was due to the ingenious Sir -Christopher Wren, who in this connexion has not hitherto received -the recognition that is his due. Dr. Wren, as he was designated at -the time, was one of the most active members of the recently formed -Royal Society, and was responsible for many new experiments in -several sciences. It is clear from references in the _Philosophical -Transactions_ that his first experiments were done in 1659, and the -following statement is made by Dr. Thomas Sprat in his _History of -the Royal Society_, published in 1667: - -“He was the first author of the Noble Anatomical Experiment of -Injecting Liquors into the Veins of Animals. An Experiment now -vulgarly known; but long since exhibited to the Meetings at Oxford, -and thence carried by some Germans, and published abroad. By this -Operation divers Creatures were immediately purg’d, vomited, -intoxicated, kill’d, or reviv’d according to the quality of the -Liquor injected: Hence arose many new Experiments, and chiefly that -of Transfusing Blood, which the Society has prosecuted in sundry -Instances, that will probably end in extraordinary Success” (p. 317). - -Sir Christopher Wren did not actually carry out any transfusion -experiments on his own account. This was done by his friend, Richard -Lower, well known for his work on the anatomy of the heart, who -worked in the laboratory of Thomas Willis at Oxford. In these -experiments, some account of which was published in 1666, he used a -silver cannula for obtaining continuity between the artery of one -animal and the vein of another. Lower must therefore receive the -credit for having done the first transfusion actually performed in -England. In the following year other experiments were done by Dr. -Edmund King and Thomas Cox, both of whom recorded their experiences -in the _Philosophical Transactions_. - -Meanwhile Wren’s work had become known in other countries, and it is -said that transfusion was performed in 1664 by Daniel of Leipsic, -who thus anticipated the work of Lower. However this may be, the -first transfusion done upon a human being was certainly carried out -in France by Jean Denys of Montpellier, physician to Louis XIV. This -is admitted in the _Philosophical Transactions_, but the following -statement in extenuation of English hesitancy is made: - -“We readily grant, They were the first, we know off, that actually -thus improved the Experiment; but then they must give us leave to -inform them of this Truth, that the Philosophers in England had -practised it long agoe upon Man, if they had not been so tender in -hazarding the Life of Man (which they take so much pains for to -preserve and relieve), nor so scrupulous to incurre the Penalties of -the Law, which in England, is more strict and nice in case of this -concernment, than those of many other Nations are.” - -Dr. Edmund King further asserts that “We have been ready for this -Experiment these six Months,” that is to say, since March, 1667. -Moral precedence must, however, give way to the actual, and it is -clear that Denys had snatched the laurels. A translation of a full -and interesting account of his earlier experiment upon animals -and his first two transfusions done upon men was published in the -_Philosophical Transactions_ for July 22, 1667. Of the first of these -he wrote as follows: - -“On the 15 of this Moneth, we hapned upon a Youth aged between 15 -and 16 years, who had for above two moneths bin tormented with a -contumacious and violent fever, which obliged his Physitians to bleed -him 20 times, in order to asswage the excessive heat. - -“Before this disease, he was not observed to be of a lumpish dull -spirit, his memory was happy enough, and he seem’d chearful and -nimble enough in body; but since the violence of his fever, his -writ seem’d wholly sunk, his memory perfectly lost, and his body so -heavy and drowsie that he was not fit for any thing. I beheld him -fall asleep as he sate at dinner, as he was eating his Breakfast, -and in all occurrences where men seem most unlikely to sleep. If he -went to bed at nine of the clock in the Evening, he needed to be -wakened several times before he could be got to rise by nine the next -morning, and pass’d the rest of the day in an incredible stupidity. - -“I attributed all these changes to the great evacuations of blood, -the Physitians had been oblig’d to make for saving his life, and I -perswaded myself that the little they had left him was extreamly -incrustated [? incrassated] by the ardour of the fever.... -Accordingly my conjecture was confirmed by our opening one of his -Veins, for we beheld a blood so black and thick issue forth, that it -could hardly form itself into a thread to fall into the porringer. -We took about three ounces at five of the Clock in the morning, and -at the same time we brought a Lamb, whose Carotis Artery we had -prepar’d, out of which we immitted into the young man’s Vein, about -three times as much of its Arterial blood as he had emitted into the -Dish, and then having stopt the orifice of the Vein with a little -bolster, as is usual in other phlebotomies, we caus’d him to lie down -on his Bed, expecting the event; and as I askt him now and then how -he found himself, he told me that during the operation he had felt a -very great heat along his Arm, and since perceiv’d himself much eased -of a pain in his side, which he had gotten the evening before by -falling down a pair of staires of ten steps; about ten of the clock -he was minded to rise, and being I observed him cheerful enough, I -did not oppose it; and for the rest of the day, he spent it with much -more liveliness than ordinary; eat his Meals very well, and shewed a -clear and smiling countenance.... He grows fat visibly, and in brief, -is a subject of amazement to all those that know him, and dwell with -him.” - -This boy had been transfused for therapeutic purposes; the second -transfusion performed by Denys was done upon an older man “having -no considerable indisposition,” and was purely experimental. About -twenty ounces of lamb’s blood are stated to have been transfused, -but the procedure was without any ill effect, and it may be doubted -whether the man received as much as this. - -In the succeeding number of the _Philosophical Transactions_, October -21, 1667, the remarks of another French experimenter, Gaspar de -Gurye, are quoted. These are of considerable interest, as they -contain the first warning of the dangers attending the administration -of incompatible blood. De Gurye affirms “that an expert Acquaintance -of his, transfusing a great quantity of blood into several Doggs, -observed alwayes, that the Receiving Doggs pissed Blood.” - -Other cases were subsequently recorded by Denys. In one he claims -to have cured a patient suffering from “an inveterate Phrenzy.” His -account of it is too long to be quoted here in full, but it is of -special interest in that it contains the first account of hæmolysis -and the attendant symptoms in man which follow the transfusion of -incompatible blood. The blood of a calf was used in this instance and -on two occasions; at the first transfusion only a small amount was -given, but at the second, - -“the Patient must have received more than one whole pound. As this -second Transfusion was larger, so were the effects of it quicker -and more considerable. As soon as the blood began to enter into his -veins, he felt the like heat along his Arm and under his Arm-pits -which he had felt before. His pulse rose presently, and soon after -we observed a plentiful sweat all over his face. His pulse varied -extremely at this instant, and he complained of great pain in his -Kidneys, and that he was not well in his stomack, and that he was -ready to choak unless they gave him his liberty. - -“Presently the Pipe was taken out that conveyed the blood into his -veins, and whilst we were closing the wound, he vomited store of -Bacon and Fat he had eaten half an hour before. He found himself -urged to Urine, and asked to go to stooll. He was soon made to lie -down, and after two good hours strainings to void divers liquors, -which disturbed his stomack, he fell asleep about 10 a Clock, and -slept all that night without awakening till next morning, was -Thursday, about 8 a Clock. When he awakened, he shewed a surprising -calmness, and a great presence of mind, in expressing all the pains -and a general lassitude he felt in all his limbs. He made a great -glass full of Urine, of a colour as black, as if it had been mixed -with the soot of Chimneys.” - -The hæmoglobinuria, which was not at that time attributed to its -true cause, cleared up in the course of a few days, and the patient -appeared to be greatly benefited. - -Although the first transfusion performed upon a human being was done -in France, similar experiments were shortly afterwards carried out in -England. The passage already quoted concerning the “sundry instances” -mentioned in Sprat’s _History of the Royal Society_ is amplified by -the diarist, Samuel Pepys, who witnessed the experiments on at least -one occasion. His first reference to the subject is under the date -November 14, 1666: - -“Here [at the Pope’s Head] Dr. Croone told me, that, at the meeting -at Gresham College to-night, ... there was a pretty experiment of the -blood of one dogg let out, till he died, into the body of another on -one side, while all his own run out on the other side. The first died -upon the place, and the other very well, and likely to do well. This -did give occasion to many pretty wishes, as of the blood of a Quaker -to be let into an Archbishop, and such like; but, as Dr. Croone -says, may, if it takes, be of mighty use to man’s health, for the -amending of bad blood by borrowing from a better body.” (_Diary_, ed. -Wheatley, vi. p. 60.) - -Two days later he reports: - -“This noon I met with Mr. Hooke, and he tells me the dog which was -filled with another dog’s blood, at the College the other day, is -very well, and like to be so as ever, and doubts not its being found -of great use to men,--and so do Dr. Whistler, who dined with us at -the tavern.” (Ibid., p. 63.) - -On November 28 there was further conversation at Gresham College to -the same effect (ibid., p. 79). In the following year the experiments -were taken a stage further, and Pepys refers again to them under the -date November 21, 1667: - -“Among the rest they discourse of a man that is a little frantic, -that hath been a kind of minister, Dr. Wilkins saying that he hath -read for him in his church, that is poor and a debauched man, that -the College have hired for 20s. to have some of the blood of a sheep -let into his body; and it is to be done on Saturday next. They -purpose to let in about twelve ounces; which they compute, is what -will be let in in a minute’s time by a watch. They differ in the -opinion they have of the effects of it; some think it may have a good -effect upon him as a frantic man by cooling his blood, others that it -will not have any effect at all. But the man is a healthy man, and by -this means will be able to give an account what alteration, if any, -he do find in himself, and so may be usefull.” (_Diary_, vii. p. 195.) - -On November 29 Pepys dined at a house of entertainment, and enjoyed -good company. - -“But here, above all, I was pleased to see the person who had his -blood taken out. He speaks well, and did this day give the Society a -relation thereof in Latin, saying that he finds himself much better -since, and as a new man, but he is cracked a little in his head, -though he speaks very reasonably, and very well. He had but 20s. -for his suffering it, and is to have the same again tried upon him: -the first sound man that ever had it tried on him in England, and -but one that we hear of in France, which was a porter hired by the -virtuosos.”[3] (Ibid., p. 205.) - -The subject of this experiment was Arthur Coga, an indigent Bachelor -of Divinity of Cambridge, aged about thirty-two. It is recorded in -the _Philosophical Transactions_ that the experiment was performed by -Richard Lower and Edmund King at Arundel House on November 23, 1667, -in the presence of many spectators, including several physicians. -Coga, when asked why he had not the blood of some other creature -transfused into him, rather than that of a sheep, replied: “Sanguis -ovis symbolicam quandam facultatem habet cum sanguine Christi, quia -Christus est agnus Dei.”[4] It was estimated that Coga received eight -or nine ounces of blood, but he seems to have felt no effects, good -or ill, and it is probable that he did not actually receive as much -as this. - -These beginnings in England and France led to the more frequent use -of blood transfusion, but soon afterwards the operation fell into -disrepute. Disasters followed the transfusions, and the practice also -met with violent opposition on the ground that terrible results, -such as the growth of horns, would follow the transfusion of an -animal’s blood into a human being. In consequence of this they were -actually forbidden in France by the Supreme Court until the Faculté -of Paris should signify its approval, but the necessary permission -was not given. The “extraordinary success” predicted by Sprat and the -sanguine expectations of Pepys and his friends were destined not to -be fulfilled until a later age. - -For more than a hundred years the possibilities of blood transfusion -were almost entirely neglected. There are some isolated references -to it in medical writings towards the end of the eighteenth century, -but of these it is only necessary to notice two. In 1792, at Eye in -Suffolk, blood from two lambs was transfused by a Dr. Russell into -a boy suffering from hydrophobia, and he claimed that the patient’s -recovery was to be attributed to the treatment. Soon afterwards -in 1796 Erasmus Darwin recommended transfusion for putrid fever, -cancer of the œsophagus, and in other cases of impaired nutrition. -He suggested that the blood should be transferred from donor to -recipient through goose quills connected by a short length of -chicken’s gut, which could be alternately allowed to fill from the -donor and emptied by pressure into the patient. This operation he -never actually performed. - -[Illustration: Fig. 1.--BLUNDELL’S IMPELLOR - -From _Researches Physiological and Pathological_, 1824] - -A more general interest in the subject was revived in England by -the work of James Blundell, lecturer on physiology and midwifery at -St. Thomas’s and Guy’s Hospitals. He published in 1818 his earliest -paper on experimental transfusion with a special form of syringe -invented by himself. His first apparatus consisted of a funnel-shaped -receptacle for the blood, connected by a two-way tap with a syringe -from which the blood was injected through a tube and cannula into the -recipient. His experiments were performed upon dogs, and he began by -drawing blood from the femoral artery and re-injecting it into the -same animal through the femoral vein. He then conducted a long series -of investigations into the properties of blood, the effects of its -withdrawal, and the resuscitation of an exsanguinated animal. Soon he -had opportunities of transfusing patients with human blood, and the -results are recorded in his paper of 1824. His apparatus had by then -been elaborated, and an engraving of his _Impellor_, as he termed -it, is reproduced here. It consisted as before of a funnel-shaped -receptacle for the blood, but the syringe was now incorporated in -one side of the funnel, and contained a complicated system of spring -valves, which caused the blood to travel along the delivery tube when -the piston was pushed down. The Impellor was fixed to the back of a -chair in order to give it stability. - -All the patients transfused by Blundell were either exceedingly -ill, or, judging from his description, already dead, so that his -results, considered statistically, were not favourable! Nevertheless, -he was not discouraged, and stated his “own persuasion to be that -transfusion by the syringe is a very feasible and useful operation, -and that, after undergoing the usual ordeal of neglect, opposition, -and ridicule, it will, hereafter, be admitted into general practice. -Whether mankind are to receive the first benefit of it, in this or -any future age, from British surgery, or that of foreign countries, -time, the discoverer of truth and falsehood, must determine.” -Blundell’s work has been described in some detail because, after the -experimental work of the seventeenth century, the year 1818 may be -taken to mark the real beginning of the clinical application of blood -transfusion. - -The chief difficulty in the way of successful transfusion was, of -course, the obstacle introduced by the coagulation of the blood. -Bischoff in 1835 sought to overcome this by injecting defibrinated -blood, and that solution of the difficulty was adopted by many -operators, including Sir Thomas Smith, who, in 1873, used -defibrinated blood for transfusing a case of melæna neonatorum at -St. Bartholomew’s Hospital. The apparatus on this occasion consisted -of “a wire egg-beater, a hair sieve, a three-ounce glass aspirator -syringe, a fine blunt-ended aspirator cannula, a short piece of -india-rubber tubing with a brass nozzle at either end connecting the -syringe with the cannula, a tall narrow vessel standing in warm water -for defibrinating the blood, and a suitable vessel floated in warm -water to contain the defibrinated blood.” Others, too numerous to be -individually named, used the same method throughout the nineteenth -century and during the first ten years of the twentieth. Even in -1914 a method of using defibrinated blood was described by Moss. An -objection was raised in 1877 that it was dangerous to do this, owing -to the excess of fibrin ferment introduced with blood thus treated, -but this did not greatly discourage its use. Then, as now, one of the -chief uses of blood transfusion was found to be in the practice of -obstetrics. A series of 57 cases of this kind were reported by Martin -of Berlin in 1859, 43 of these having been successful. A further -series of cases was collected by Blasius in 1863. He was able to -report that of 116 transfusions performed during the previous forty -years, in 56 the results were satisfactory. These statistics did -not indicate a remarkable degree of success. Fatalities due to the -transfusion had occurred, attended by the symptoms which we have now -learned to associate with incompatibility of the transfused blood. -At that time, however, the deaths were believed to be due chiefly to -the introduction of air bubbles into the circulation, although it had -been shown experimentally by Blundell in 1818, and again by Oré in -1868, that small quantities, such as might be accidentally introduced -during a transfusion, produced no ill effects. Some explanation, -however, was required, and so air bubbles for a long time received -the blame. - -[Illustration: Fig. 2.--MR. HIGGINSON’S TRANSFUSION INSTRUMENT - - A is a metallic cup, of 6-oz. capacity, to receive the supply of - blood. B an outer casing, which will hold 5 oz. of hot water, - introduced through an aperture at C. D is a passage leading into - an elastic barrel, composed of vulcanized india-rubber, E, of - which the capacity is 1 oz. F′ the exit for the blood into the - injection-pipe G. At D and F there are ball-valves, capable of - closing the upper openings when thrown up against them, but leaving - the lower openings always free. The blood, or other fluid, poured - into the cup A, has free power to run unobstructed through D, E, F; - a small plug H is therefore provided to close the lower aperture - F when necessary. The tube G is of vulcanized india-rubber, and - terminates in a metal tube O for insertion into the vein. This - diagram is one-half the actual size of the instrument.] - -Although some of the early experiments on blood transfusion had -been done in England, and although its revival in the nineteenth -century was initiated in England, yet it is to be noticed that most -of the references to it up to 1874 are to be found in the works of -Continental writers. Nevertheless, an important modification was -introduced into the technique of the operation in 1857 by Higginson, -who applied the principle of a rubber syringe with ball-valves for -transferring the blood from the receptacle into which it was drawn, -to the vein of the recipient. This apparatus is illustrated here, -as it is of some interest in the history of medicine. Higginson’s -syringe is now used for a different purpose, but it was successfully -applied by its inventor in a series of seven cases which he duly -reported. One patient whom he transfused was suffering from extreme -weakness, which was attributed to the too protracted suckling of -twins. He gave her about twelve ounces of blood from a healthy female -servant, and a state of quietude followed her previous restlessness. -A few minutes later the patient was seized with a rather severe -rigor. It did not last long, but led to a state of reaction and -excitement, in which she sang a hymn in a loud voice. The final -result was good, and Higginson reports that in five of the seven -cases some benefit was to be attributed to the transfusions. Later -the same principle was used in America by Aveling and by Fryer about -the year 1874, and subsequently it was in that country that nearly -all the important advances in the science of blood transfusion were -made. - -In 1873 an inquiry was carried out by the Obstetrical Society of -London into the merits of transfusion, the subject having been -brought to the Society’s notice by a report of a case by Aveling, -and an interesting summary of the evidence was prepared by Madge -in 1874. The results do not seem to have been very encouraging, -and transfusion was still regarded as a procedure that was only to -be used as a last resource. Even at this date the blood of other -animals was being used for transfusion, although the practice had -been discredited by Panum in 1863 and by others, and a series of -cases was reported by Hasse in 1873, in which lamb’s blood was given -for various conditions. Other cases were reported from Italy (3) and -Russia (101). Sentiment, if not science, seems to have suggested -that there was something repulsive in bringing a lamb into the sick -chamber and mixing animal with human blood, but it was remarked in a -discussion on the subject that “it was only taking lamb in another -form.” - -After 1875, however, there was a decline in the amount of attention -given to transfusion which lasted for thirty years. This was -probably due in part to the increasing number of fatalities which -had followed the more general use of transfusion, but, as Peterson -suggests, it was also to be accounted for by the increasing use of -normal saline solution for intravenous injection in the treatment -of hæmorrhage. There was also a period during which the use of milk -was advocated for intravenous therapy (37, 279). Soon after the -beginning of the twentieth century transfusion received a fresh -impetus which has steadily gained force up to the present time. The -free use of cannulæ and syringes had always been hampered by the -coagulation of the blood, and it was clearly a great advance to be -able to perform a direct transfusion without the intervention of any -tube. This was made possible by great improvements in the surgery -of the blood-vessels, which were due in the first place to the work -of Murphy, published in 1897; they were carried still further by -others, such as Carrel and Guthrie, and culminated in the work of -Crile, who in 1907 put the technique of direct transfusion on a -securer basis than it had ever been before. His method is briefly -described in a later chapter of the present work. Meanwhile the chief -factor responsible for previous fatalities was being eliminated. -The presence of agglutinins and iso-agglutinins in the blood had -been detected by Landsteiner and by Shattock in 1901; in 1907 the -four blood groups into which human beings can be classified were -determined by Jansky and the work was repeated by Moss in 1910. - -Simplification of the group tests soon followed, as is described -in another chapter. At the same time great improvements were made -in the use of syringes, paraffined tubes, and in anastomosis of -the blood-vessels. In this connexion one of the most notable -contributions was made by Curtis and David, who in 1911 introduced -the use of syringe transfusion through a two-armed tube coated on the -inside with paraffin. In 1913 indirect transfusion by means of the -paraffined vessel was introduced by Kimpton and Brown, and it was -now evident that blood transfusion was shortly to become a method of -treatment which would be without any very difficult technique, and -could therefore be more extensively applied. - -The final advance was made in 1914, when the use of sodium citrate -as an anticoagulant was made possible by the work of Lewisohn in -America, of Hustin in Belgium, and of several others, who all arrived -independently, but almost simultaneously, at the same conclusion. -The use of an anticoagulant was no new idea. In 1858 the use of -small quantities of ammonia had been suggested by B. W. Richardson -in the _Guy’s Hospital Reports_, and in 1869 sodium phosphate was -used in four obstetrical cases by Braxton Hicks, who found that the -process was greatly facilitated thereby; but neither of these methods -came into general use. It had long been known that hirudin or leech -extract, and the salts of oxalic acid or of citric acid, could be -used as anticoagulants outside the body, but their supposed toxicity -had prevented their being used for transfusion. The proof that sodium -citrate was both efficient for this purpose and non-toxic in a -dilution that was still effective at once raised blood transfusion to -a wider sphere of usefulness than had been possible before. The first -transfusion of citrated blood was performed by Professor L. Agote of -Buenos Aires, on November 14, 1914, a date which is therefore of the -greatest importance in the history of blood transfusion. A method had -at last been discovered which approached the ideal, since it united -the four cardinal virtues of simplicity, certainty, safety, and -efficiency. - -This great stride forward in the technique of blood transfusion -coincided so nearly with the beginning of the war that it seemed -almost as if foreknowledge of the necessity for it in treating war -wounds had stimulated research. Yet during the first two years -of the war almost nothing was known in the British Army of its -possibilities. I have no evidence that the French or German army -doctors were any better informed than ourselves. Some attempt was -made in 1916 to introduce the use of direct transfusion through -cannulæ, but the technique was too difficult and uncertain for the -stress of war conditions. It was not until 1917, when the British -Army Medical Corps was being steadily reinforced with officers from -the United States of America, that knowledge of blood transfusion -began to be spread through the Armies. A conspicuous part was borne -by Oswald Robertson in introducing the use of the citrate method, -and to him a very large number of men indirectly owe their lives. -In some armies the paraffined vessel of Kimpton and Brown remained -the favourite method, but to me the citrate method seemed the more -suitable, because of the certainty with which success could be -attained, and the same view was taken by many others. At the same -time the investigators appointed by the Medical Research Committee -attempted to elucidate the problems connected with hæmorrhage and -wound shock, and their results, as will be seen, served to confirm -the estimate already being formed of the value of blood transfusion. - -In this way a large number of operators in this country became -familiar with the various methods, and transfusion has in consequence -been used increasingly in civilian practice since the war. It is -undoubtedly destined to figure still more largely in the therapeutics -of the future. Meanwhile the public mind is becoming gradually more -used to the idea, and the time is past when every transfusion is -deemed worthy of a sensational headline in a newspaper. Nevertheless, -at the end of the year 1920 the following advertisement appeared in -the personal columns of _The Times_: - - “Will any Doctor who knows method of treating cancer by transfusion - of child’s blood kindly write Box --.” - -So the wheel is come full circle, and the shade of Pope Innocent VIII -may well chuckle as he notes the small advance in popular knowledge -since the fifteenth century. - - - - -CHAPTER II - -INDICATIONS FOR BLOOD TRANSFUSION - - -The indications for blood transfusion are gradually becoming more -numerous as experience of its effects accumulates, and there can be -no doubt that the value of transfusion as a therapeutic measure is -destined to become much more generally recognized than it is at the -present time. Lack of knowledge, together with an exaggerated idea of -the difficulties of the process, is the chief obstacle to its more -extended use. Time and the education of the rising generation will -provide the remedy for this. - -The conditions for which blood transfusion may be used fall into four -well-defined groups. On the one hand are those characterized by an -acute anæmia, which demand the performance of a blood transfusion -as an emergency or life-saving operation; on the other hand are -those in which the anæmia is of slow onset, and is to be combated -by a single transfusion to tide the patient over an operation or a -critical period or by repeated transfusions in the hope of prolonging -the patient’s life if not of obtaining a cure. A third group includes -the hæmorrhagic diseases in which the transfusion is administered not -only to replace blood which has been lost, but also to bring about -cessation of the hæmorrhage. A fourth group includes cases of general -toxæmia, whether chemical or bacterial, in which the new blood is -given partly on account of its therapeutic properties, partly in -order to dilute the circulating toxins or to supply healthy red blood -cells to carry on the oxygenation of the tissues. - -For the first and third of these groups blood transfusion is -now very firmly established as a method of treatment which is of -extraordinary value. For the second group it may be regarded as a -palliative to be given with circumspection. For the fourth group -administration of blood is still in the experimental stage. - -In the present work each condition will be taken in turn and, as -far as possible, separately, though at the outset it has been found -undesirable to dissociate the two conditions, hæmorrhage and shock. -The present position of blood transfusion in relation to each -condition will be discussed; its limitations and the precautions to -be observed will be described. - - -HÆMORRHAGE AND SHOCK - -Blood transfusion is pre-eminently the best form of treatment that -is known for the condition of acute anæmia following hæmorrhage to -whatever cause it may be due. Its good effects were seen by a number -of operators in many hundreds of exsanguinated patients during the -latter part of the war, and its value was then established upon -a secure foundation. It was unusual during the war to meet with -patients who were in danger of their lives from loss of blood alone -without the additional factor of traumatic shock, but such cases did -occur, and they are also to be met with in civil practice, as, for -instance, in attempted suicide by throat cutting, in gastric ulcer -with severe hæmatemesis, and in secondary hæmorrhage after operation. -The more typical condition following war wounds, hæmorrhage with -shock, will be faithfully reproduced in the victims of train or -street accidents, in patients who have undergone certain severe -operations, and in women suffering from post-partum hæmorrhage or a -ruptured ectopic gestation. - -The signs and symptoms of acute anæmia will be familiar to most -readers. It is characterized by a peculiar greyness of the skin, by -extreme pallor of the mucous membranes, by a cold perspiration, by a -thready and rapid pulse which may exceed 140 beats to the minute, -and by extreme restlessness. The “amaurosis” of the text-books -is seldom met with, but in the last stages the patient becomes -semi-unconscious, the restlessness tends to disappear, the muscles -relax, and the respiration takes on a peculiar sighing character, -which is described as “air hunger,” and probably indicates exhaustion -of the respiratory centre. Meanwhile, if instruments are at hand, -additional signs may be recognized. The most important of these is a -fall in blood pressure. It has been stated that a systolic pressure -below 70 mm. of mercury is scarcely compatible with life, but this -is not in accordance with experience. It was common during the war -to meet with blood pressures below 45 mm., so low in fact that they -could not be measured with the ordinary apparatus that was available, -but many patients whose lives had reached even so low an ebb as -this were quickly restored by the administration of blood, provided -that the exsanguinated state had not lasted for too long a time. -If the medullary centres are damaged beyond recovery by inadequate -oxygenation lasting for several hours, then no treatment is of any -avail. But provided that it be given before this length of time -has elapsed, a blood transfusion may succeed in saving life at any -stage of the condition. Its efficacy is indeed only limited by the -actual cessation of the patient’s heart beats. I have successfully -treated a patient who before transfusion could only be described as -moribund. He was almost unconscious, absolutely blanched, and his -radial pulse imperceptible; his jaw was relaxed and his breathing had -become a series of fish-like gasps, such as are only associated with -imminent dissolution. His heart would certainly have ceased beating -within a few minutes, yet his condition improved so rapidly after -transfusion that an hour later it was possible, with the help of a -second transfusion, to amputate his leg above the knee. This patient -ultimately recovered, having been as near death as it is possible to -be and yet remain alive. - -The results of a blood transfusion upon a patient suffering from -acute anæmia are, indeed, amongst the most dramatic effects to be -obtained in the whole range of surgery. Within a few minutes of its -commencement the whole aspect of the patient alters. His respiration -becomes deep and regular, his restlessness disappears, colour -returns to his face, his pulse rate falls, and he begins to take an -intelligent interest in his surroundings. These changes taking place -within a period of fifteen minutes may well strike an onlooker as -little short of miraculous. Shortly afterwards the patient may fall -into a natural sleep, a sure sign that the normal circulation has -been restored to the exhausted central nervous system. - -In considering how much blood should ordinarily be given in the -treatment of acute anæmia, experience is a safer guide than any -theoretical considerations. Nevertheless, it is worth while to -inquire briefly into the experimental and theoretical basis upon -which the treatment of acute anæmia rests. It is difficult to -estimate accurately the total quantity of blood in the body of an -adult, but it has been variously stated by physiologists to be -from a twentieth to a tenth part of the body weight, or, in liquid -measure, from 3 to 6 litres (approximately 5 to 10 pints). This -has been estimated in several ways, the results of which show some -discrepancy. A figure approaching the higher one was obtained long -ago by the direct method of washing out the blood from the bodies -of executed criminals. Recently it has been claimed by Haldane that -these determinations were inaccurate; by means of his carbon monoxide -method, with the details of which we are not concerned here, he has -estimated that the blood volume is but one-twentieth of the body -weight, or in very stout persons is even as low as one-thirtieth. -Still more recently Haldane’s estimation has been challenged in -its turn by observers who have injected a dye into the circulation -and have then determined its degree of concentration in the blood -by means of colorimetric comparisons. It is evident that if the -dilution which occurs when a known quantity of dye is injected can -be accurately estimated, then the total volume of circulating fluid -can be calculated. This method could not be used until a non-toxic, -non-diffusable dye had been discovered, but it was found in 1915 that -“vital red” fulfilled these requirements (143). The results obtained -in this way show that those originally given by the direct method -were substantially correct. The blood volume was found to vary from -1/13 to 1/10·5 of the body weight; on the average it amounted to -5,350 cc., or 85 cc. per kilogram of body weight. These observations -have been in their turn criticized (114), but only to the extent -of reducing the amount by 1/10. It may therefore be assumed that, -according to the most recent work, the blood volume is from 5 to 6 -litres, or, approximately, 8 to 10 pints. - -It is a still more difficult matter for obvious reasons to estimate -how much blood a man can lose and yet remain alive. This will depend -partly on the power of physiological accommodation possessed by the -individual in his vaso-motor system and tissue fluids and partly -on the rapidity with which the bleeding takes place. Clinical -observations have shown that after a moderate hæmorrhage, such as -the withdrawal of 800 cc. of blood from a donor, the blood volume -may be restored to normal within an hour. If, on the other hand, the -hæmorrhage is excessive, a condition results in which the normal -process of rapid restoration of volume fails, and the circulation -remains in a dangerously depleted condition. The heart attempts to -keep the blood pressure at an adequate level by an increase in its -rate, but it is in effect attempting to circulate a small volume of -fluid in a vascular system which has become too big for it. Imperfect -oxygenation of the medullary and cerebral centres with exhaustion of -the heart results, and this is accompanied by all the symptoms of -anæmia which have been already described. - -If the initial hæmorrhage be very rapid, death may result almost at -once, since the physiological processes may have no time to act. On -the other hand, a rapid hæmorrhage may under certain circumstances -save the patient’s life, for the immediate syncope which results -produces so great a fall in the blood pressure that hæmorrhage almost -ceases and a clot may form in the lumen of the divided vessel. If the -hæmorrhage be more gradual, the physiological compensation may at -first be adequate to maintain the blood volume, but finally a point -is reached at which this process fails and the patient then passes -into the condition of acute anæmia. - -The actual amount of blood therefore that must be lost to be -fatal will vary according to circumstances. Experience shows that -hæmorrhage may take place into the peritoneal or pleural cavities -to the extent of two litres or even more, and it may be stated as a -rough guess that 2·5 litres, that is to say, even as much as almost -half the total blood volume, may be lost without immediate death -resulting. This degree of depletion could not, however, be endured -for long. A series of clinical observations made by Keith by the -vital-red method upon the blood volume in soldiers suffering from the -combined effects of hæmorrhage and wound shock showed that in the -most serious cases the volume was below 65 per cent. of the normal, -frequently even between 50 and 60 per cent. Serious symptoms followed -a reduction to between 65 and 75 per cent. In patients without -distressing symptoms the volume was never below 75 per cent. of the -normal. There is direct evidence, therefore, that those patients who -are most in need of treatment, such as a transfusion of blood, will -probably have lost from 25 to 50 per cent. of their blood volume, -that is to say, 1·5 to 3 litres in amount, and will need from 750 cc. -to 1·5 litres to restore them to, or near to, the 75 per cent. level -at which the compensatory processes can begin to regain their power. - -It is thus possible to arrive at a theoretical basis on which an idea -can be formed of the amount of blood that should be given in acute -anæmia. Practical experience is in agreement with the theory, and it -will now be easier to understand how it is that in treating acute -anæmia no attempt need be made to replace the whole amount of blood -that has been lost, or indeed anything approaching it. In an extreme -case 2 to 3 litres of blood will have been lost and 1 litre or more -will be needed to restore the blood volume to approximately 75 per -cent. of the normal. A case of this sort, however, is fortunately -not often to be met. One has already been described on page 21; -this patient received altogether nearly 1,600 cc. of blood in two -transfusions, and 1,000 cc. of normal saline were given in addition. - -In most cases of severe hæmorrhage the patient has probably not lost -more than 1,400 to 1,800 cc. of blood, and 600 to 800 cc. will be -enough to restore the balance of the circulation. This is in practice -the amount of blood that is commonly administered, and it is well -within the limits of what a single blood donor can afford to lose. -If a more definite standard be required, it may be laid down that -in a single transfusion for acute anæmia 750 cc. of blood should -be given. If, in an exceptional case, more than this is needed, a -second transfusion should be performed with a similar amount taken -from another donor. Sometimes it may happen that a patient already -_in extremis_ from loss of blood, needs a severe operation; in such -a case a second transfusion may be given with great advantage at -the conclusion of the operation. The first transfusion will restore -the patient sufficiently to render the performance of an operation -possible; the second will combat the additional shock and hæmorrhage -which it has caused. - -It has already been stated that it was uncommon during the war to -meet with patients who were suffering from anæmia uncomplicated by -traumatic shock. It was in fact the condition of shock which tended -to dominate the clinical picture, and it was towards the elucidation -of the facts concerning shock, its causation, prevention, and -treatment, that the investigations co-ordinated by the Medical -Research Committee were mainly directed. These investigations were -carried out both in the laboratory and in the military hospitals, and -considerable additions were made to the knowledge of the condition. -It is necessary to give some account of the conclusions which were -reached in order that the rôle of blood transfusion in the treatment -of shock may be fully understood. - -Hæmorrhage and shock cannot be dissociated, and this is not only -because they so frequently occur together in the same patient, but -also because the manifestations of the two conditions are essentially -the same. In shock, as in hæmorrhage, are found the same pallor -of the face and mucous membranes, the same fall of blood pressure -and rapid pulse, the same perspiration, restlessness, and shallow -respiration. The symptoms following a severe hæmorrhage have -sometimes been referred to as constituting a “shock-like condition.” -As will be seen, however, it is more accurate to describe the -symptoms of shock as closely resembling those of hæmorrhage, and to -regard both conditions as a manifestation of deficient fluid content -in the circulation. - -Numerous theories have been advanced to account for the symptoms -seen in shock. Until recent years it was customary to suppose -the vaso-motor centres had failed, being overcome by exhaustion -consequent upon excessive stimulation by a greatly increased number -of afferent impulses from the periphery of the body. It was suggested -that as a result there was a general dilatation of the vascular -system, especially in the abdominal veins, and therefore a general -impairment of the circulation. Various hypotheses were, in addition, -formulated, to account for the vaso-motor failure. These included -the ideas of deficient carbon dioxide in the blood, exhaustion -of the adrenal secretion, and exhaustion of nerve-cells in the -higher centres. All these theories found their supporters and much -experimental evidence was brought forward, but none was susceptible -of final proof. The whole theory of vaso-dilatation and the idea that -the patient “bleeds into his own abdominal veins” were eventually -disposed of by observation of the clinical facts. Many extensive -abdominal operations have been performed upon shocked patients, but -the accumulation of blood in the splanchnic area has never been -demonstrated. It has, on the other hand, been found that in the limbs -the arteries and arterioles are strongly contracted. It is also by -no means unusual to meet with the condition known as venospasm; the -veins are collapsed and their walls contracted, so that it becomes -necessary to use a considerable positive pressure before any fluid -can be induced to flow into them. It has, in addition, been shown -that the vaso-motor system is still active, and the heart, although -beating rapidly, still responds to reflex stimulation and to increase -of intracranial tension. - -It becomes necessary, therefore, to find some other explanation of -the low blood pressure which is the essential feature of shock. Of -especial value in this connexion are the investigations by Keith, -already mentioned, into the changes in blood volume found in soldiers -suffering from shock and hæmorrhage. In very few of these cases -were the symptoms due to shock alone, but usually the loss of blood -volume was much greater than could be accounted for by the amount -of hæmorrhage which had taken place. Here, therefore, was evidence -strongly suggesting that the symptoms of shock are due to actual -loss of circulating fluid, and the problem now resolved itself into -a search for this fluid which has ceased to be part of the effective -blood volume. Enough has already been said to show that there is no -evidence that the larger vessels, whether arteries or veins, are -acting as reservoirs in which the blood is stagnating. It therefore -only remains to consider whether the capillary system is capable, -under abnormal conditions, of holding so large a proportion of the -blood as has been shown by Keith to have left the circulation. For -a discussion of this problem the reader may be referred to W. B. -Cannon’s summary of the arguments (45), from which it becomes clear -that the capillary system may be regarded as a potential reservoir -large enough to contain the lost blood in shock. The question is, -however, further complicated by the fact that the capillary blood in -shock differs from the circulating blood in containing an abnormal -concentration of corpuscles. Extensive observations made on wounded -soldiers have shown that the number of red blood cells may rise even -to 8,000,000 per cmm. in the capillary blood, while the number in -the venous blood remains at 5,500,000 or less. This concentration of -the red cells is gradual and progressive, and will by itself account -for a large part of the loss of volume, since normally the bulk of -the blood is made up of corpuscles and plasma in approximately equal -parts. The stagnation is, moreover, accentuated by the increased -viscosity of the blood resulting from the concentration, and by the -chilling of the surface of the body, which is always a feature of -the state of shock. A vicious circle is thus established, and the -symptoms of shock become severe as the capillary stagnation becomes -more pronounced. - -A second factor which may also play its part in the loss of blood -volume in the general circulation is the exudation of some of -the plasma into the surrounding tissue spaces. As the stagnation -increases, oxygenation decreases, and the walls and the capillaries -become more permeable, so that some fluid is probably lost in this -way. This permeability may also be accentuated by the increased -hydrogen-ion concentration in the blood, which often accompanies -shock, but it seems to be clear that this is a secondary phenomenon -resulting from imperfect oxygenation in the tissues, and it will -therefore not be regarded as one of the factors responsible for -shock. Further fluid is lost by the copious perspiration commonly -seen in shock. There seems, therefore, to be a conspiracy between a -whole set of different factors all tending to deprive the patient -of his circulating fluid. The net result is a condition so closely -resembling hæmorrhage that it may be impossible to distinguish the -two, this difficulty being increased by the fact that they so often -occur together. - -In the foregoing account of the production of shock the fate of -the lost blood has been discussed, but nothing has been said of -the factors initiating the capillary stagnation. This is a subject -which is of great interest and some obscurity, and is of evident -importance in considering how shock may be avoided. The present -treatise, however, is primarily concerned with the treatment of -shock when already established, and it is therefore not proposed to -follow out the other question in detail. An injury may be followed -immediately by a condition of “primary wound shock,” in which the -patient becomes suddenly pale and pulseless. This is a physiological -reaction, which may be transient, and it is to be distinguished -from the much more serious condition of “secondary wound shock” -which appears some time later. It is this secondary shock alone -which has been under consideration in the preceding pages. The chief -importance of the primary shock lies in the fact that it may initiate -the conditions which predispose to secondary shock, so that under -certain circumstances the one may become merged in the other. These -predisposing conditions are increased evaporation from the skin, a -general fall in the temperature of the body, mental anxiety, and the -continued stimulation of the higher centres by afferent impulses as -is manifested by pain. The condition of secondary wound shock was -shown in a striking degree, during the earlier years of the war, -by the men suffering from fracture of the femur. In the later part -of the war warmth was supplied more systematically than before to -the seriously wounded, and all fractured femurs were treated at an -early stage with Thomas’s splints. Two of the factors predisposing -to shock, namely cold and pain, were in this way to some extent -eliminated, and it was very striking how much better than before was -the general condition of the patients on arrival at the hospitals. - -Nevertheless, the elimination of these factors, which is a simpler -matter in civil life than it was under conditions of war, will not -avert all shock in a large proportion of cases. It is necessary, -therefore, to find some additional factor which will initiate shock -in addition to the predisposing causes. It is thought that this -may have been identified in a substance of obscure nature which is -derived from the damaged tissues themselves, and which, circulating -in the blood, is able directly to affect the capillary system. Just -as the shock following severe burns is believed to be due to the -circulation of a toxic substance formed by the burning of the skin -and other tissues, so the shock following severe trauma is believed -to be of toxic origin, the toxin being derived from damaged tissues, -muscle being particularly active in this respect. The condition -may, therefore, be one of “traumatic toxæmia,” in which there is a -general loss of capillary tone throughout the body, so that “the -blood percolates into the network of channels as into a sponge.” -The circulating blood is thus rapidly depleted, and the symptoms -of shock become established. The investigation of this source of -shock was carried out chiefly by Dale, Bayliss and Cannon (65), who -were able to reproduce the condition of shock in animals by the -injection into their circulation of a substance obtained from damaged -muscles. To this substance the name histamine was given. It would be -a mistake, however, to suppose that because a substance producing -shock experimentally has been obtained from muscles, that therefore -this is the identical substance which is responsible for every case -of traumatic toxæmia. Extreme shock may be produced when but little -damage has been done to muscles. Probably damage to any tissue of -the body if extensive enough will produce a substance or substances -which will give rise to the symptoms, and it may be a long time -before these are isolated and identified. That the last word on the -production of shock is still far from being uttered is shown by the -fact that profound shock may be induced without doing any appreciable -damage to tissue, namely, by handling and exposing the abdominal -viscera. - -It may be this traumatic toxæmia which will account for many cases of -post-operative shock, but it has been shown that some anæsthetics, -such as chloroform or ether, will of themselves greatly accentuate -shock initiated by other causes. - -It has already been mentioned that the increased hydrogen-ion -concentration in the blood, which results from imperfect oxygenation -in the tissues, is not itself a cause of shock, but it will aggravate -shock due to other factors. A discussion of this will be found in the -paper by W. B. Cannon already referred to. - -The present state of knowledge concerning the causation of shock -having been thus briefly reviewed, the question of the treatment -of the condition may be discussed. In this connexion the value of -blood transfusion will be considered. It will have become clear -that essentially the condition to be combated in treating shock is -one of lowered blood pressure following upon a diminution of the -volume of blood in the circulation. All the factors which have been -mentioned in considering the causation of shock must be combated. -Warmth must be supplied, morphia administered, fractures efficiently -immobilized, damaged tissues excised: but clearly all these measures -are prophylactic rather than curative. None of them will remove -a state of profound shock once established, for they will not of -themselves restore the blood volume depleted by capillary stasis. -It is necessary, therefore, to attack this condition directly. It -may with justice be compared to a state of acute anæmia following -hæmorrhage, but with this difference, that the blood is still present -in the body and will return to the circulation when the capillary -stasis has been abolished and the circulating balance has been -restored. The possibility of recovery from shock depends upon how -long the condition has existed. After a certain time the toxæmia, -whether the primary traumatic toxæmia or the secondary increase in -hydrogen-ion concentration, appears to have a damaging effect upon -the capillary walls, so that an increased loss of fluid takes place -into the tissues and this cannot be remedied. It is essential, -therefore, to use the means which will most rapidly restore the -circulation and bring about a rise in blood pressure which will be -permanent. It is reasonable to infer that the most hopeful means of -bringing this about is by a blood transfusion, which will actually -replace the blood temporarily lost. This is the physiological remedy, -and its value has been proved by the results obtained in many cases -of my own as well as in those recorded by others. The efficiency of -the treatment is accentuated by the fact that so large a proportion -of cases of shock are associated with, and aggravated by, some degree -of hæmorrhage. Apart from this, Keith’s observations have shown -that the diminution of blood volume in shock is comparable with -that which attends severe hæmorrhage. The state of shock in fact so -closely resembles hæmorrhage that most of the same remarks concerning -blood volume and the amounts that should be given by transfusion -may be applied, and it is unnecessary to repeat them here. It must -be remembered, however, that in pure shock the amount of hæmoglobin -in the body is not reduced though there is less in the circulation. -It is restored to the circulation when the capillary stagnation is -overcome. This will be referred to again later on. - -During the war the value of blood transfusion in shock was amply -demonstrated. In civilian practice I have found it to be of value -when given after operations such as removal of the rectum, whether -by the perineal or abdomino-perineal route, amputation of the leg -through the hip joint, or removal of a sarcoma from the nasopharynx. -Transfusion should be given towards the close of the operation -before the evidences of shock have reached their maximum. The -depletion of the blood volume is then actually remedied as it takes -place, and transfusion becomes almost as much a prophylactic measure -as warmth and the administration of morphia. - -It is probable that the mortality following very severe operations -such as those mentioned above would be considerably reduced if blood -transfusion were to be given as a routine measure. Reference has -already been made to the bad effect of the ordinary anæsthetics, and -the best effects are obtained by a blood transfusion in conjunction -with gas and oxygen or with spinal anæsthesia. It is necessary, -however, to draw attention to the fact that a blood transfusion if -given to a patient under the influence of a spinal anæsthetic must -not be performed until the operation is very nearly completed, for it -will very often produce a much more rapid return of sensation than -would otherwise occur. - -In advocating the use of blood transfusion to combat the effects -of shock and hæmorrhage, it would be misleading to imply that this -is necessarily the only treatment that is available. Something -must be said of the substitutes for blood that have been used, and -in particular the value of gum acacia must be considered. In the -days before the war it was customary to treat post-operative shock -or hæmorrhage with large quantities of normal salt solution given -intravenously or subcutaneously. During the earlier part of the war -also this was used, and there can be no doubt that for the less -severe cases this treatment is often beneficial. Occasionally even -the lives of patients who were desperately ill have been saved by -it; I have seen a saline infusion cause the recovery of a man who -had a dozen perforations of the small intestine and who had, in -addition, lost several pints of blood intraperitoneally from a wound -of a large mesenteric vessel. Such cases are, however, exceptional. -In the presence of severe shock or hæmorrhage a saline infusion may -cause an immediate rise in blood pressure, but the fluid exudes so -rapidly into the tissues that the effect is usually very transient. -This fact is universally admitted to be true and need not be further -emphasized. Saline solution administered by the rectum is likely to -have a more lasting effect, but the process of absorption is slow, -and the patient may be dead before it has had time to act. The -same applies to water given by the mouth. A patient suffering from -severe shock is unable to tolerate more than a very small quantity -of fluid in his stomach without vomiting. Some success was attained -by Oswald Robertson in treating cases of hæmorrhage by the method of -“forced fluids,” large quantities being given by the mouth and by -the rectum (245). In many serious cases, however, this treatment is -inapplicable, and it is clear that transfusion is more rapid and more -certain in its effect. Isotonic saline having been found ineffectual, -it was suggested that a hypertonic solution (2 per cent. sodium -chloride) might be of more value. This was tested clinically and in -the laboratory, and was found to have no advantage over the isotonic -solution (11). - -When the association of increased hydrogen-ion concentration with -shock was demonstrated, it was at first supposed to be one of the -factors producing the condition. It was therefore natural that the -effect of a solution of sodium bicarbonate (4 per cent.) should -be tried. The effect upon certain cases suffering from extreme -“acidosis” and air hunger was very striking, but in general the -alkaline solution was no more effective than the ordinary isotonic -saline. I soon abandoned its use for intravenous infusion, but it was -of service in serious cases when given by the rectum. - -During the war the necessity for the conservation of time--and -of blood--was evident. The search for a satisfactory substitute -for blood was therefore prosecuted with great energy, most of the -research being done by, or under the direction of, Professor W. M. -Bayliss. The object of the research was to discover a non-toxic -solution which possessed the same “viscosity” as the blood, and the -same osmotic pressure due to contained colloid. It was believed that -such a solution would not tend to exude so rapidly into the tissues -and would therefore augment the blood volume more effectively than -the fluids previously used. After many experiments it was claimed -in 1916 that a blood substitute had been found in a 6 per cent. -solution of gum acacia with ·9 per cent. sodium chloride. It was -even stated on the evidence of laboratory experiments that the gum -solution was as effective as blood in the treatment of shock and -hæmorrhage. It was therefore used very extensively among the wounded, -and favourable reports upon its value were made by various workers. -It is difficult, however, to control the results in giving treatment -of this kind. If a patient dies after being given a gum infusion, -no one can state definitely that he would have lived had he been -given a blood transfusion instead. If a patient lived after having a -blood transfusion, it would be equally rash to state that he would -have died had he been given gum. Nevertheless, after giving the gum -solution a number of trials, I formed the opinion that the results -were inferior to those obtained with blood. Patients did not recover -whom from previous experience with blood transfusion I should have -expected to do so. I accordingly continued to use blood in preference -to gum whenever it was available, although justice must be done to -those who so strongly advocated gum by saying that there can be -no doubt that it is very much more effective than other solutions -previously used. The same opinion was formed by many other surgeons, -although it was natural to feel a bias in favour of gum which could -be given with much greater economy of time and effort than blood. Up -to the present time I have seen no reason for altering this opinion, -and should always prefer to treat hæmorrhage and shock with a blood -transfusion if possible. - -Recently the relative values of a number of intravenous infusions -for shock have been put to an extensive experimental test by F. C. -Mann. The shock was produced by handling the abdominal contents, -and the effect on the blood pressure of the various fluids was -mechanically registered. The conclusion was reached that far the best -results were obtained by a transfusion of blood or blood serum, the -effect of these being more permanent than that of any other substance -used. The use of gum acacia was found to give results which were -“variable and sometimes disastrous,” but this may have been due to -some extent to errors in the technique of preparing the solution. - -This draws attention to a possible objection to the use of gum, -namely, that some samples of the solution have been found to be -actually toxic; but it is said that this can be avoided if proper -care be exercised in its preparation. Full instructions for this are -given in a paper by S. V. Telfer. - -Into the discussion of the relative merits of blood and gum solutions -may be profitably introduced the further question as to which is the -more valuable constituent of transfused blood, the corpuscles or the -plasma. It has been seen that the essential factor in producing the -symptoms of shock and hæmorrhage is a reduction of blood volume, -and treatment is therefore directed in the first place towards the -restoration of this volume, with a fluid of the same viscosity and -osmotic pressure as blood. This might be done with plasma or, some -may say, equally well with gum. From the point of view only of -volume, the corpuscles and plasma are of equal value, since each -forms approximately half the total volume of a given quantity of -blood. There is, however, another aspect to be considered. One of -the results of loss of blood volume is imperfect oxygenation in the -tissues. When the volume is increased by the addition of plasma or -gum, the corpuscles in the circulation are diluted, and this by -itself would tend further to impair oxygenation. The dilution is, -however, compensated for by the improvement in circulation which -in its turn improves the supply of oxygen to the tissues, and it is -still further counteracted by the restoration to the circulation of -the blood corpuscles which were stagnating in the capillary system. -It seems clear that these successive processes will be accelerated -by the use of a fluid which itself contains corpuscles, and this may -afford a theoretical explanation of the clinical observation that -blood is more effective than gum. Its use will tend to establish -more quickly the “virtuous circle” following increased volume, and -so undo the “vicious circle” due to insufficient volume. It has -been questioned whether the corpuscles of transfused blood really -do play an active part in the economy of their new host, or whether -their new environment may not quickly render them effete. This has -been answered by the exceedingly interesting and ingenious series of -experiments carried out by Winifred Ashby. She has transfused blood -of a known group (see Chapter IV) into an individual of a different, -but compatible group, and then shown that it is possible by selective -agglutination with a suitable serum to demonstrate the presence in -the blood of the two kinds of corpuscles side by side. In this way -she has shown that transfused corpuscles are still present in the -circulation and of normal appearance thirty days after they were -introduced. - -It is therefore justifiable to make the inference that transfused -corpuscles can for some little time carry out their normal function. -If it be true that their presence is an advantage in the treatment -of deficient blood volume, it may also be conjectured that their -presence is likely to be of greater importance in treating hæmorrhage -than it is in the treatment of pure shock, for in the latter -condition all the original corpuscles are still present in the body, -while in the former they are not. - -I should sum up the discussion of the relative merits of blood -and gum by saying that on the grounds of experiment and clinical -experience I believe blood to be the more efficient of the two, -particularly in the most serious cases. Every patient who needs it -should therefore have the advantages conferred by blood transfusion -if it can be done. If it cannot, then gum and saline is much the most -satisfactory substitute that is at present known. - -Some of the concluding remarks in the foregoing pages will have -suggested that the use of gum infusion may be considered of more -value in treating pure shock than in treating hæmorrhage. For this -reason, apart from other diagnostic considerations, it may be of -importance to be able to distinguish clinically between shock and -hæmorrhage. Attention has already been drawn to the fact that the -symptoms and appearance seen in a patient suffering from severe shock -very closely resemble those seen in hæmorrhage. It may, in fact, be -impossible to say from purely clinical evidence whether a patient is -suffering from shock, or hæmorrhage, or both. A case which recently -came under my own observation well illustrates this point. A very -stout, elderly man had fallen down a lift-shaft and was brought into -St. Bartholomew’s Hospital soon after the accident. He appeared -to have fallen on his feet, and the lower ends of both tibiæ had -been driven through the inner sides of his soles, but there were no -other signs of injury. His general condition on arrival at hospital -was fairly good, but all the usual measures were taken to minimize -shock. An hour or two later he had passed into a condition of extreme -collapse, and exhibited all the symptoms which have already been -described. Not much hæmorrhage had taken place from the wounds in -his feet, and the question arose as to whether his present condition -was due to internal hæmorrhage from visceral injury, or whether it -was due chiefly to shock. His abdomen contained so much fat that no -evidence could be obtained from an examination of it, and it was in -fact impossible to arrive at any conclusion. There could, however, -be no question of performing any operation, and the patient made -no response to other treatment. At the autopsy it was found that -there were fractures of the ribs, spinal column, and symphysis -pubis in addition to the injuries to the legs. There was very little -hæmorrhage in connexion with any of the fractures, and it appeared -that death was to be attributed almost entirely to shock. This was -perhaps a somewhat unusual case, in which no help could be derived -from an examination of the patient, but similar difficulties will -sometimes be met. - -It might be expected that a criterion would be supplied by an -examination of the blood. The results from this, however, have proved -to be disappointing. The facts have been investigated by Cannon and -others (47) and may be summarized as follows. The number of red -corpuscles in the blood from the capillaries of the ear or finger has -been found to be invariably raised in patients suffering from shock. -A blood count may show an increase up to seven million red cells per -cmm. or even more. The blood in the venous circulation, however, of -the same patient is more dilute, the count being less by one to two -million red cells. When the shock is complicated by hæmorrhage, the -blood count in the venous system will again be lower than that in -the capillaries, but in both the counts will be less than if there -were no hæmorrhage. The differences are, however, not so great or -so constant that any principle can be laid down by which the two -conditions may be distinguished. In patients in whom hæmorrhage is -the outstanding feature the blood counts will be still lower, but -the capillary and venous difference will still be present. It was -found that in hæmorrhage the hæmoglobin percentage, and therefore the -colour index, tended to be lower than in shock, but this was most -obvious when the hæmorrhage had been very severe, and in such cases -the diagnosis is usually clear from other evidences. The clinical -difficulty lies in the distinction between cases of pure shock and -of shock complicated by considerable hæmorrhage. It seems that -little help is to be derived from an examination of the blood. This -difficulty in diagnosis can only influence treatment in the direction -of giving blood rather than gum-saline, though the latter would -probably be effective for many of the cases of shock if they could be -distinguished. - -The effects of transfusion for hæmorrhage and shock are to be -judged best by the clinical results. The abnormal distribution -of the corpuscles is altered by the treatment with a consequent -redistribution in the circulation. No constant changes, therefore, in -the blood count follow transfusion, and no exact mathematical effect -can be demonstrated. It has been shown by Huck that sometimes the -immediate rise in the blood count is greater than can be accounted -for by the amount of blood given. This is often followed by a fall, -which is succeeded in its turn by a second rise. These results are -to be explained by alterations in the amount of destruction and -formation of red cells going on in the body. That is to say, they are -biological rather than mechanical, and are at present but imperfectly -understood. - -In the foregoing discussion hæmorrhage and shock have been considered -in a general way. Something must now be said of the particular -conditions for which transfusion may be given. Concerning traumatic -hæmorrhage and shock there is little to be added, for these -conditions present the general features of the problem in its least -complicated form. No clear-cut rule can be laid down as to the point -at which transfusion becomes necessary. The blood pressure is perhaps -the best single indication, and if this has fallen below 80 mm. -(systolic), then a transfusion is certainly indicated. Apart from -this, the patient’s general condition is the safest guide. As soon as -it becomes evident that his life is in danger, a transfusion should -be given. Better save a few lives by many transfusions than lose them -by reserving transfusion for those who are actually moribund. - -Secondary hæmorrhage following an operation is fundamentally similar -to primary hæmorrhage, but may present a few additional points. In -recent years by far the largest number of transfusions for secondary -hæmorrhage have been given for bleeding from septic amputation -stumps. In many cases of this sort it is no easy matter to stop the -bleeding by ligaturing a bleeding vessel; sometimes it is impossible. -Nevertheless, transfusion should not be withheld owing to a risk of -increased hæmorrhage supposed to follow a rise in blood pressure. -Usually the patient is debilitated by prolonged suppuration, and -often his blood is deficient in its power of coagulation. It has -been found that a transfusion, in addition to replacing some of the -blood that has been lost, tends to improve the patient’s resistance -to micro-organisms, and to shorten the coagulation time of the blood. -Recurrence of the hæmorrhage is therefore discouraged on the whole, -and in many cases a series of transfusions for recurrent hæmorrhages -has saved a patient’s life when the prognosis had seemed to be almost -hopeless. - -Post-operative hæmorrhage associated with chronic jaundice is another -condition which demands special consideration; this will be dealt -with later under the heading of hæmorrhagic diseases. - -The proper treatment of severe hæmorrhage from a gastric or duodenal -ulcer has always puzzled physicians and surgeons alike. It is -probably true that patients very seldom die as the result of a -single rapid hæmorrhage, even if severe. There can, however, be no -doubt that death due actually to acute anæmia may follow repeated or -prolonged hæmorrhage. Hitherto treatment has been conducted mainly -on medical lines. Opinion is now, however, tending to favour earlier -and more frequent surgical interference, and this can be made a -less dangerous procedure by giving a preliminary blood transfusion -to improve the patient’s general condition. When the patient’s life -is threatened by hæmorrhage repeated or prolonged, transfusion is -undoubtedly the best means of saving him. Here again the fear of -restarting the hæmorrhage by raising the blood pressure has acted as -a deterrent, so that transfusion is apt to be withheld until too -late. Nevertheless, it is clear from the numerous cases recorded in -the literature that this fear is groundless (130, 215, etc.). The -effect of a transfusion on the coagulating power of the patient’s -blood more than compensates for the risk attending a rise in blood -pressure. Now only is lost blood replaced, but also the clot plugging -the damaged vessel is made more secure. The patient is tided over -the immediate danger to his life, and surgical treatment is made -possible. This view will doubtless meet with much adverse criticism, -but its justice will eventually be recognized. - -As in the early days of transfusion, so at the present time, a -considerable proportion of the patients that need transfusion will -be met with in the course of obstetrical practice. It has often -been remarked how much blood can be lost by a woman following the -delivery of her child without any serious result; nevertheless, -many deaths are occasioned every year by post-partum hæmorrhage, -placenta prævia, and rupture of an ectopic gestation. Sometimes the -bleeding is so rapid that there is no margin of time available for -a transfusion unless all the facilities be immediately at hand. -Short of this, transfusion is the ideal treatment, and the problem -is a simple one, the relief of acute anæmia being the only object -in view. One interesting modification of the procedure has been -recently recommended by German writers, namely, the reinfusion of the -patient’s own blood. This is applicable only when the hæmorrhage has -taken place into the peritoneal cavity, and is therefore limited to -the treatment of a ruptured liver or spleen, a ruptured uterus, or -a tubal abortion. With a ruptured uterus the sterility of the blood -is not assured, and this condition were better not included. For the -other conditions Lichtenstein recommends that the blood should be -ladled out of the peritoneal cavity into Ringer’s solution and then -strained to remove clots. The resulting fluid is infused into a vein. -Judging from my own experience of intraperitoneal hæmorrhage, not -much blood would actually be recovered in this way, since usually -so much of it has clotted. In any case, the whole procedure is to be -looked upon with suspicion owing to the unknown and probably profound -changes that have taken place in partially clotted blood. Eberle -records that in one case reinfusion was followed by hæmolysis, and -among twenty-one cases reported by Schweitzer in 1921, one death -was attributed to the reinfusion, which, as in Eberle’s case, was -followed by hæmoglobinuria. Transfusion has also been used for the -toxæmias of pregnancy, but this will be dealt with under another -heading. - - - - -CHAPTER III - -INDICATIONS FOR BLOOD TRANSFUSION--_continued_ - - -HÆMORRHAGIC DISEASES - -It is claimed that blood transfusion provides an efficient means of -treatment in most conditions distinguished by symptoms of spontaneous -hæmorrhage or by traumatic hæmorrhage which cannot be controlled. All -such diseases have the common features that the coagulation time of -the blood is abnormally prolonged, and it may be supposed that the -transfused blood supplies some missing constituent, so that for the -time the blood is enabled to coagulate more normally. Most of the -evidence available shows that the claims made for transfusion are not -exaggerated. - - -=Jaundice.=--It is well known how exceedingly dangerous an operation -upon a jaundiced patient may be owing to the difficulty of obtaining -hæmostasis. The coagulation time of the patient’s blood is not -affected in a transient catarrhal jaundice, but in the chronic -condition it has been shown to be three or four times the normal -(223). In these circumstances it is found that a transfusion is -of some use in shortening the coagulation time of the patient’s -blood so that bleeding ceases, although sometimes, especially in -cases of jaundice due to malignant disease in which the biliary -obstruction has not been relieved by the operation, the effect is -very transitory, and after two or three days the patient may again -begin to bleed (215). No other method of overcoming this has yet been -found to be more effective than transfusion, though the intravenous -administration of calcium compounds is sometimes of value. - - -=Hæmophilia.=--Blood transfusion is of still greater value when the -coagulation time of the blood is prolonged owing to a congenital -deficiency, as in hæmophilia. It is unnecessary to discuss here -in detail the precise nature of the deficiency. No definite -conclusion has yet been reached, though it seems to be clear that -the abnormality resides in the organic clotting complex, and not -in the calcium content of the blood. Treatment, therefore, will -aim at supplying the deficient substance, so that the coagulation -time may be reduced to normal, whereupon the bleeding will cease. -Various methods of bringing this about have been used. Horse serum or -whole blood injected subcutaneously has often been found effective -and sometimes even when used merely as a local application. Not -infrequently, however, horse serum fails of its effect, so that no -reliance can be placed upon it. Even when effective, the alteration -in coagulation time is transitory, a fact which introduces an obvious -objection to its use, for if the occasion should arise, as it easily -may, for a repetition of the treatment, the patient may be exposed to -the risk of severe anaphylactic shock. - -Another form of treatment has been introduced by H. W. C. Vines, in -which a slight anaphylactic shock is deliberately induced, the result -of this being a fall in the coagulation time of the blood to normal. -The mechanism of this change is at present unexplained. Again, the -effect is transitory, but for a certain period afterwards a surgical -operation may be safely performed upon a hæmophilic patient treated -in this way. This method has not yet been extensively tested, and in -any case it cannot be used in an emergency, for the patient must be -sensitized by a preliminary injection and an interval of several days -allowed to elapse before the anaphylaxis can be produced. - -The efficiency of blood transfusion in the treatment of hæmophilia -has been very often demonstrated, and seems at present to afford -the most certain means that we possess of arresting the symptoms. -Presumably the transfused blood supplies directly the deficient -factor in the coagulation complex, and it has been shown by Bernheim -(1917) that the transfusion even of quite a small amount of blood -will almost immediately stop the bleeding. In addition to comparative -certainty and rapidity in action, transfusion has the advantage -that it will replace the blood which has been lost, for often the -patient has reached a stage at which he is in danger of his life -from actual anæmia. This treatment, therefore, will always be useful -in an emergency, whether the patient be bleeding to death from a -slight wound, or whether he be suffering from acute appendicitis and -so is in need of an immediate operation. If transfusion does not at -once stop the bleeding, the treatment can be repeated, so that the -patient should not be allowed to die from loss of blood. In most -cases the bleeding will eventually stop if the patient’s life can -be prolonged. Even if the treatment be immediately successful, the -transfused blood necessarily contains only a limited quantity of the -substance necessary for the coagulation complex, and this gradually -disappears. Again, therefore, the effect is transitory, so that -transfusion is in no sense curative. It has been noticed that the -tendency of a hæmophilic to bleed decreases as age advances, and it -has been suggested by Ottenberg and Libmann that small quantities of -blood should be injected into his veins at regular intervals of one -to three months. It is possible that in this way he might be brought -safely through the more perilous years of his life. - -The proof of the effect of transfusion upon the coagulation time -of the blood rests upon the evidence of a number of independent -observers. Pemberton has recorded a case of a hæmophilic whose -coagulation time before transfusion was estimated to be 23 minutes. -Blood was given to the amount of 500 cc., and 5 minutes later the -coagulation time was 3 minutes. Twelve hours later it was 8 minutes, -and on the fourth day after transfusion it had risen again to 20 -minutes. - -Other observations have been made as follows: - - -------------+-----------------------------+---------- - | Coagulation time. | Minutes. - -------------+-----------------------------+---------- - Bulger | Before transfusion | 82 - | 1 day after transfusion | 10 - | 8 days ” ” | 8 - | 25 ” ” ” | 40 - -------------+-----------------------------+---------- - Minot & Lee | Before transfusion | 150 - | After ” | normal - | 3 days after transfusion | 60 - | 5 ” ” ” | 100 - -------------+-----------------------------+---------- - Addis | Before transfusion | 245 - | After ” | 24 - | 25 days after transfusion | 200 - | After 8 cc. serum injected | 38 - -------------+-----------------------------+---------- - -In treating jaundice or hæmophilia the transfusion may be performed -by the method of choice described in Chapter VII of the present work. -The addition of an anticoagulant to the blood does not render it any -less efficient as a hæmostatic agent. In all cases the coagulation -time of the patient’s blood is found to be reduced after transfusion, -whether sodium citrate be used as an anticoagulant or not. The -explanation of this may be found in the fact referred to on p. 120, -that the citrate is very rapidly destroyed in the circulation, and -so cannot for long influence adversely the hæmostatic properties of -normal blood. - -The seeming paradox of using an anticoagulant in an endeavour to -promote the coagulation of the blood is heightened by the work of -Ottenberg, who has shown that the coagulation time may be reduced by -the intravenous injection of sodium citrate alone. In this experiment -20 cc. of a 3 per cent. solution of sodium citrate were injected into -a hæmophilic, whose coagulation time had been found to be 85 minutes. -Ten minutes after the injection it was found to be 25 minutes. Two -days later it had risen again to 85 minutes. This observation has -not been confirmed but, if it be true, citrated blood is likely to be -actually more efficient in the treatment of hæmophilia than untreated -blood. - -The amount of blood to be transfused in hæmophilia will vary with -the age of the patient and according to whether he is suffering from -acute anæmia or not. If hæmostatic effects only are wanted, 100 cc. -of blood will be enough. If anæmia is also present, the dosage will -be governed by the same considerations as have already been discussed -in the section on the treatment of hæmorrhage. - - -=Melæna Neonatorum.=--Another hæmorrhagic condition in which blood -transfusion is of the very greatest value is that known as _melæna -neonatorum_. Severe hæmorrhage takes place from the bowel of an -infant, sometimes only a few hours after birth. The cause is quite -unknown, but it is found that absolute hæmostasis is usually brought -about by blood transfusion. Horse serum has often been successfully -used as in treating hæmophilia, but blood transfusion again has -the additional merit that the blood which has been lost is thereby -replaced. A single transfusion is usually enough, as the hæmorrhage -does not tend to recur when once it has been stopped. For a newly -born infant, even if _in extremis_, only a small quantity of blood -is needed, so that a transfusion of 50 to 100 cc. is usually found -to be enough. Bruce Robertson suggests that, as a good working rule, -the amount should not exceed 15 ccm. per pound of body weight. The -superficial veins of an infant are exceedingly small, so that the -introduction even of a fine needle into the median basilic may be -matter of the greatest difficulty. The best method of transfusing an -infant, therefore, demands special consideration. A description of -this will be found on p. 134 of the present work. - -The value of transfusion for _melæna neonatorum_ has not been very -generally recognized, but a number of striking cases have been -reported. Defibrinated blood had been used in 1873 by Sir Thomas -Smith as described in Chapter I, but the first case in which whole -blood was used was published by Lambert in 1908. Later, in 1910, -Welch, and then Schloss, recommended the subcutaneous injection -of serum or of blood, but these measures were clearly not so -effective as the intravenous transfusion of blood, as has been -testified by numerous observers (Lespinasse, Unger, Vincent, Graham, -Bruce Robertson, Lapage, Hutchinson, etc.). The patients may be -actually moribund, for a new-born infant can only afford to lose -a relatively small amount of blood, but even then transfusion is -often successful. Bruce Robertson reports that of a series of forty -cases of hæmorrhagic disease of the new-born which were treated -by transfusion, all recovered except four; of these two died from -associated umbilical sepsis, one from intracranial hæmorrhage, and -the fourth had already ceased breathing when the treatment was begun. - -It has sometimes been stated that for transfusing an infant either -parent can be safely used as blood donor, on the assumption that the -serum reactions are not yet developed. This may sometimes be true, -but the fallacies and possible dangers of this are explained in a -later chapter. - -A case was recently reported by R. D. Laurie, who, knowing that he -himself belonged to Group IV, drew 20 ccm. of his own blood into a -syringe containing five grains of sodium citrate in solution. This he -injected into a vein in the infant’s arm; the small size of the vein -he had chosen made this difficult, but the treatment resulted in the -rapid recovery of the patient. - - -=Purpura.=--Of all the forms of hæmorrhagic diseases, the two already -described, hæmophilia and melæna neonatorum, are the only ones for -which blood transfusion is a really effective remedy. It is probable -that under the somewhat general term “purpura hæmorrhagica” are -grouped several conditions, all of very obscure origin, none of -which are conspicuously benefited by transfusion. Many transfusions -have been given for purpuric symptoms, chiefly in America. Several -cases are reported by Bernheim, and twelve transfusions were given -to seven patients by Peterson. In some of these the treatment -produced a temporary improvement, but usually they relapsed after -an interval of a few months. One of Bernheim’s patients appears to -have owed his life for the time being to a transfusion, but he died -subsequently during a recurrence. Two cases are reported by Graham. -One was not benefited at all; the other improved for a time, but -afterwards relapsed. In a serious case, therefore, transfusion may -be worth trying; it has indeed been stated by Ottenberg and Libmann, -observers with a wide experience of transfusion, that this treatment -is “definitely curative” in severe cases of purpura. At the present -time there is little to add on the subject, but it is possible that -further advances will be made by proceeding on these lines. - - -BLOOD DISEASES - -=Pernicious Anæmia.=--Blood transfusion has been advocated for -several conditions characterized by alterations in the cells of -the patient’s blood. It has been used in the treatment of aplastic -anæmia, splenic anæmia, chlorosis, and leukæmia, but in none of these -diseases has it been of much avail. In pernicious anæmia, however, -transfusion has proved to be of very great service. - -It is, indeed, now a recognized form of treatment for this disease, -though the numerous reports upon results that have been published -have not pronounced unanimously in its favour. Variability in -results probably depends to some extent upon the difficulty of -distinguishing true pernicious anæmia from some forms of secondary -anæmia. It is hardly to be expected that much benefit would follow -blood transfusion in the undiagnosed secondary type, since the -destruction or loss of corpuscles is continuous until the cause has -been removed. In true pernicious anæmia, on the other hand, there may -be remissions in the disease, and it is quite clear that these may -be initiated or prolonged by blood transfusion. The largest number -of consecutive cases that has been recorded was treated in the Mayo -Clinic in the years 1915 to 1918 (Archibald, Pemberton, Hunt). It was -estimated that in about 60 per cent. of the patients with pernicious -anæmia a definite improvement followed transfusion. It is generally -agreed that the best results are seen in those who have not yet -reached the last stages of the disease, though sometimes patients -who are actually _in extremis_ will also show great improvement. A -remarkable instance of this has been reported in Norway (261). A -man, aged thirty-three, was dyspnœic, semi-conscious, and moribund -when admitted to hospital. His red cells numbered 850,000 per cmm., -and his hæmoglobin percentage was 19. Immediate improvement followed -the transfusion of 900 cc. of citrated blood, the red cells rising -quickly to 2,000,000 and later to 3,000,000. Twelve days after -admission he was walking about. No case must therefore be regarded as -hopeless, though disappointments must be expected. - -As a general rule blood transfusion should be given before the -more serious secondary manifestations of the disease have shown -themselves, that is to say, some time before the condition has -become dangerous to life. Probably the disappointing results of this -treatment have partly been due to the fact that it has been regarded -as a last resort and has often been given at too late a stage. No -rule can be laid down as to when transfusion should be given, but -common sense suggests that it should be tried as soon as it is -evident that the disease is progressing in spite of other methods -of treatment. One authority (Anders) even advises that transfusions -should be given as soon as an assured diagnosis has been made, but he -weakens his case by adding that other methods of treatment should be -used at the same time. If the patient is already seriously ill when -first seen, the blood transfusion should be tried at once, as its -effect, if beneficial, is likely to be more rapid than that of any -other form of treatment. - -The amounts of blood given in pernicious anæmia have varied. Massive -doses have occasionally been given (179), but the general opinion -seems to favour smaller amounts, 300-500 cc., the dose being repeated -at intervals of two or three weeks. Repeated transfusions have been -an outstanding feature of the treatment, and as many as thirty-five -transfusions of 500 cc. or more have been given to one patient, -extending over a period of thirty months. This is in itself a -demonstration of the fact that blood transfusion does not cure the -disease; the beneficial effect of each transfusion may wear off in -a short time, but by repeating the treatment the patient’s life can -be prolonged for months or even years beyond the time when it would -otherwise have ended. - -Although the effect of transfusion is apt to be transient yet it is -certain that its good effects are due not merely to the addition -of a certain number of healthy corpuscles to the circulation, but, -in addition, to an obscurer factor. This can best be expressed by -saying that the transfused blood appears to have a stimulating -effect upon the blood-forming tissues of the patient, so that more -red corpuscles are discharged into the circulation. One observer -believes that enumeration of the reticulated red cells may be used -as an indication of the hæmopoietic powers of the bone marrow (289). -The reticulated appearance is assumed to be characteristic of cells -which have recently entered the circulation. The mode in which this -stimulus acts is unknown, and the whole subject calls for further -investigation. That this does take place is well illustrated by the -following details of three cases from Dr. Drysdale’s wards at St. -Bartholomew’s Hospital. The transfusions were given by Dr. Joekes, -who was also responsible for the estimations of the corpuscles. - -[Illustration: Fig. 3.--PERNICIOUS ANÆMIA, CASE I] - -I. A woman, aged 51, had been treated for four years for pernicious -anæmia, and when admitted to hospital was becoming steadily worse. -The red corpuscles numbered 1,470,000 per cmm., and her hæmoglobin -percentage was 32 on October 21, 1918, and by November 19 they had -fallen to 750,000 and 25. On November 22 she was transfused with 500 -cc. of citrated blood, and a blood count made immediately afterwards -showed that she then had 1,410,000 red cells per cmm. On December -12 the number had risen to over 3,000,000, and on January 28 of the -following year it was over 4,000,000. This was still maintained -in May, 1919, and on the last occasion on which a blood count was -made she was found to have 4,400,000, with a hæmoglobin percentage -of 90. Since then she has been lost sight of, but would certainly -have returned had she relapsed. This case shows what remarkable -results sometimes follow a single transfusion and the progressive -improvement which follows the initial rise. The diagram shows the -results more graphically. - -[Illustration: Fig. 4.--PERNICIOUS ANÆMIA, CASE II] - -II. A similar result, even more striking, was obtained in a woman -aged 42. She was treated medicinally for four months, during which -time her red cells steadily decreased from 1,250,000 to 429,000 per -cmm. She was then transfused with 400 cc. of blood, and her blood -count rose immediately to 967,000. The rise continued steadily, and -three months later her blood count was 3,690,000 per cmm. Two very -small additional transfusions were given during this period, but to -what extent these helped in the treatment cannot be estimated. The -results in this case also are represented graphically by the diagram -above. - -[Illustration: Fig. 5.--PERNICIOUS ANÆMIA, CASE III] - -III. A less favourable result is illustrated by the following -history: A stores assistant, aged 47, had been ill for two years, -and was first treated for pernicious anæmia in April, 1920. He was -medicinally treated with arsenic, but no improvement followed. On -June 18, 1920, his corpuscles numbered 1,060,000 per cmm. He was -transfused with 600 cc. of blood, and his corpuscles increased at -once to 1,840,000 per cmm. A month later there had been a further -increase to 2,520,000, but this was not maintained, and nine months -afterwards he was given a second transfusion of 500 cc. of blood. -Immediately after this his red cells numbered 1,800,000 per cmm. -(April 14, 1921). There was a further slight rise and then another -rapid fall, so that on June 4, 1921, he had only 830,000 red cells -per cmm. He was then given a third transfusion of 700 cc. The effect -of this was a steady rise, and on June 17 he had 2,112,000 red cells -per cmm. A fourth transfusion of 500 cc. was given at this point, and -thereafter the improvement was maintained, with slight variations, -until, on August 4, 1921, his corpuscles numbered 3,450,000 per cmm. - -In this case the effect of the two first transfusions was -short-lived, but perseverance with the treatment brought him in the -course of two months from an extremely serious condition to a state -of comparatively good health, in which he could again for a time -go about his business. The diagram illustrates well the rise which -followed each of the later transfusions. He had again relapsed four -months later, but, unless each transfusion had chanced to coincide -with the remissions which may occur spontaneously in this disease, it -seems clear that the treatment greatly relieved him for a time. - -There is no objection to the use of citrated blood for pernicious -anæmia, so that the transfusion can be carried out in the ordinary -way described in Chapter VII. It is necessary, however, to utter a -warning as to the choice of a blood donor. It is quite clear that -in some patients, whose disease has been diagnosed as pernicious -anæmia, there is an alteration in the reactions of the serum. The -corpuscles may show an agglutination which conforms to one of the -group tests described in Chapter VI; nevertheless, it is essential in -addition that the patient’s serum should be tested directly against -the corpuscles of the proposed donor, even if he belongs to Group -IV, whose corpuscles are not agglutinated by the serum of any normal -person. I was recently asked to transfuse a patient whose disease -had been diagnosed as pernicious anæmia. Her red blood cells had -fallen to 600,000 per cmm., so that she was probably in the last -stages. Her corpuscles were agglutinated only by serum of Group -III, so that she apparently belonged to Group II. Only two donors -were available, both of whom belonged to Group IV. Nevertheless, -the patient’s serum strongly agglutinated the corpuscles of both of -them, so that I considered it inadvisable to carry out the treatment. -Similar abnormalities have been noticed by others. It seems to be -a universal experience that slight reactions are more commonly met -with after transfusion for pernicious anæmia than when it is done -for other conditions, although these do not in any way prejudice -the results that are obtained. These reactions are possibly to be -explained by abnormalities, though of slight degree, in the patient’s -serum. In a case such as I have described the reaction would -probably be very severe, if not fatal. It is possible also that a -well-marked alteration in the serum reaction is not characteristic -of the clinical entity constituting true pernicious anæmia, but in -reality indicates that there is another underlying cause for the -anæmia, such as an undiagnosed carcinoma. Dr. Joekes has recently -(August 1921) told me that he believes from his own observations that -this is actually the case, but it needs to be established by further -investigation. The connexion between malignant disease and abnormal -serum reactions is referred to elsewhere (p. 93). - -Another possible complication is introduced into the treatment by -the necessity for giving repeated transfusions. It has been noticed -that sometimes a serious reaction follows one or more of the later -transfusions of a series, even when the blood is taken from the -same donor who had been used before without ill effects. A report -on several such cases shows that this form of reaction cannot be -predicted or eliminated by the most careful testing beforehand for -reactions between the patient’s serum and the donor’s corpuscles, -though it has occasionally been so severe as actually to hasten the -patient’s death (34). This fact suggests that the reaction is not -due to the presence of agglutinins, but is rather of the nature of -an anaphylactic shock, the patient having been sensitized by a trace -of foreign protein introduced in the blood on the earlier occasions. -Possibly it may be to some extent avoided by not using the same donor -if another is available. It also emphasizes the necessity for giving -the blood slowly and cautiously, so that the transfusion may be -stopped at the first sign of a reaction in the patient. - -Very large numbers of transfusions for pernicious anæmia have been -given in the past, yet a reaction of a dangerous severity has -occurred in but few of them. This need not, therefore, be regarded as -a contra-indication for transfusion, but rather as an indication for -circumspection in giving it. Transfusion is clearly a therapeutic -measure of great value. - -Very recently it has been claimed by Waag that excellent results have -been obtained by the repeated _subcutaneous_ injection of small doses -(5 cc.) of whole blood. In an actual case which he reports, nine -injections were given twice weekly. If the claim be substantiated by -further successes, this method of treatment may eventually supplant -the more elaborate process of actual transfusion. - - -TOXÆMIAS - -_Bacterial Infections_ - -=Pyogenic.=--The value of vaccines and bactericidal sera in pyogenic -infections, though not in universal favour, is strongly advocated -by many competent authorities, and the transfusion of blood from an -immunized donor suggests itself as a natural corollary. A quantity of -blood taken from a vigorously reacting man and given to a debilitated -patient should theoretically supply him with a large amount of -the antibodies of which he stands in need. During the war it was -found that transfusion enabled an exsanguinated patient better to -withstand the attacks of pyogenic and putrefactive organisms in -his wounds, but this was probably due to the improvement in the -general circulation which resulted rather than to any bactericidal -properties in the transfused blood. It is known that outside the body -blood has considerable powers of inhibiting the growth of bacteria, -but ordinarily it does not possess bactericidal properties. It has -been claimed, on the other hand, that the best criterion of the -degree of immunity in an immunized animal is the measurement of the -bactericidal power of its blood. There is justification therefore -for attempting to combat a pyogenic infection by the transfusion of -immunized blood. - -This method has at present not progressed beyond the stage of -preliminary trials. I have attempted it in one case, but without any -obvious benefit. The patient was a middle-aged man suffering from a -chronic staphylococcal septicæmia and a secondary anæmia. He received -a transfusion of 650 cc. of blood from a donor who had himself just -recovered from a severe infection with staphylococcus aureus. The -patient’s red blood cells underwent a temporary increase in number, -but no other result was observed. One series of nine cases has been -recorded by Fry, and in these the results leave some doubt as to -the efficacy of the treatment. Six of these patients were almost -hopelessly ill with streptococcal (five) or staphylococcal (one) -septicæmia, and only one of these responded to treatment. He received -transfusion from an ordinary donor and two from immunized donors, -who had been given five or six injections of a mixed vaccine, the -maximum dose of which contained 120,000,000 streptococci. Improvement -definitely followed the transfusions, and his recovery was afterwards -encouraged by injections of an autogenous vaccine. The other five -patients received similar treatment, but all died. The remaining -three patients had chronic suppuration, one following a streptococcal -arthritis of the knee, but no septicæmia, and all recovered. It -cannot be assumed that these recoveries were due to the transfusions. - -It is stated by Waugh that he transfused nineteen cases of pyæmia of -whom twelve recovered, and in these cases an ordinary donor was used. -No details, however, are given, so that it is not possible to make -any inferences from this. - -Greater success is claimed by Hooker, who reported that in five -cases of pyogenic infection the results were distinctly favourable. -He used immunized blood, but has formed the impression that the -transfusion even of normal blood is of value in septicæmia by -correcting the anæmia and helping to restore the normal resistance. -He recommends that if the patient has a good blood volume and a high -bacterial content in the blood, he should be bled by venesection -before transfusion. A striking case of staphylococcal septicæmia has -been recorded by Little, who believed that the patient’s recovery -was directly due to the treatment. Four transfusions were given, -the blood for three of these being taken from donors who had each -received, four days previously, an injection of vaccine made from -the patient’s own infection. Ottenberg and Libmann have treated ten -cases of pyogenic infections with transfusions. All the patients were -extremely ill and six died. It is stated that the four who recovered -“probably owe their lives to the transfusion,” but obviously it -is difficult to control the results. The same observers have -used transfusion in the treatment of infective endocarditis, but -unsuccessfully. - -Some experimental work on this subject has been carried out by Kahn. -A bacterial infection was introduced into the peritoneal cavities -of several dogs. Continuous transfusion between an infected dog -and a healthy dog was then performed, the blood passing to and fro -between the animals, sometimes for over an hour. It was found that -all the transfused animals fared better than those that were not. The -experiment suggests that resistance to infection is heightened if -two bodies can combat the infection present in one; but continuous -transfusion is scarcely practicable in man. - - -=Diphtheria.=--In the later stages of some acute diseases due to a -bacterial infection, the patient falls into a condition of acute -toxæmia, the symptoms of which resemble in some ways those of shock. -Harding has drawn attention to this condition in diphtheria; he has -produced it experimentally in animals and has treated it by blood -transfusion. The toxæmic stage was found to occur on the fourth -to the eleventh day. It was characterized by a reduction of the -output of the heart with a corresponding fall in blood pressure, -an exudation of lymph into the tissues, and an increased specific -gravity of the blood. In all these respects it resembled the collapse -due to trauma or to hæmorrhage, and it was shown by experiment that -the treatment must be directed towards increasing the amount of -effective fluid in the circulation and to decreasing its viscosity. -It was found that normal saline solution failed to do this; -gum-saline solution also failed, and tended to produce a pronounced -agglutination of the red blood cells. Blood transfusion, on the -other hand, resulted in a considerable number of recoveries. In the -aggregate more than twice as many animals survived after transfusion -as survived without it, the same amount of toxin being given in each -case. - -These experimental findings are exceedingly suggestive, but the -clinical efficacy of the treatment still remains to be proved. -Harding found that the amount of blood that should be transfused -was one-fifth of the total blood volume; the following amounts are, -therefore, recommended for the treatment of children in the toxæmia -stage of diphtheria: - - --------------+-----------+----------- - Age. | Weight. | Amount. - --------------+-----------+----------- - 1½ years. | 21 lbs. | 160 ccm. - 2 ” | 28 ” | 200 ” - 4 ” | 35 ” | 300 ” - 6 ” | 42 ” | 400 ” - --------------+-----------+----------- - - -=Pneumonia.=--A condition of toxæmia similar to that seen in -diphtheria was also observed in some of the cases of pneumonia which -complicated the influenza epidemic of 1918-19. In the United States, -among a large number of cases admitted to an emergency hospital, a -series of 28 patients, some of whom were moribund, was treated by -blood transfusion by Rose and Hund. The results were compared with -those in 21 similar cases which were not transfused. The figures -seemed to show that transfusion was of some value. Of the 28 who -were transfused, 6, or 22·4 per cent., died, and the rest recovered; -of the 21 who were not transfused, 9, or 47·7 per cent., died, and -12 recovered. The numbers treated are not large enough to afford -statistical evidence that can be relied upon, but the results were at -least encouraging. - - -=Typhoid, Measles, Tuberculosis.=--Transfusion has been tried for -several other bacterial infections with varying results. McClure has -administered immunized blood to a typhoid patient with a remarkably -good result. Ottenberg and Libmann have transfused five typhoid -patients, all of whom were desperately ill; two of them recovered. -Transfusion has also been used for intestinal hæmorrhage in typhoid, -but this is chiefly with the object of combating anæmia. Subcutaneous -injection of blood has been successfully used by Terrien in a case of -malignant measles; the donor had had measles six months previously. -Freilich has recently transfused six patients suffering from -tuberculosis, but without benefit. He is at present testing the use -of blood from donors who show a positive complement fixation test for -the tubercle bacillus. - -It is evident that treatment with immunized blood is still in -an experimental stage, but it merits further trials, all the -circumstances of which should be carefully recorded. - - -=Toxæmias of Pregnancy.=--The treatment of eclampsia by blood -transfusion was first employed by Kimpton, who speaks favourably of -the results obtained. Later it was independently suggested to Blair -Bell, who was the first to employ it in this country, by certain -investigations into the facts of immunology. It had been found that -symptoms resembling those of eclampsia could be produced in mice by -injecting into them an extract of placenta, whether from a healthy or -an eclamptic woman; the same results were obtained by injecting fresh -serum from similar individuals. Further, if the placental extract was -mixed with serum from a normal person of either sex, the effects were -not obtained, and it was inferred that the placental toxin had been -neutralized by antibodies in the serum. If, however, the placental -extract was mixed with serum obtained from the blood of an eclamptic -patient, then the toxic symptoms were obtained as before. Apparently, -therefore, the serum in eclampsia lacks certain antibodies which are -present in the serum of normal individuals. If these observations -had been correctly interpreted, it seemed reasonable to suppose -that blood from a normal person would supply an eclamptic patient -with the antibodies which she lacks. The patient treated by Blair -Bell was already comatose and apparently dying. She was given 500 -cc. of citrated blood and rapidly recovered; her convalescence was -uninterrupted. It would be unwise to found great hopes on a single -case, but the treatment undoubtedly merits further trial. - -Transfusion has also been used by Keator in treating the toxæmia -of early pregnancy, and Morel has successfully used the blood of a -healthy pregnant woman for the same purpose. Gettler recommends the -use of alkalinized blood for “acidosis” in pregnancy. At present, -however, little evidence can be adduced in favour of this form of -treatment. - - -=Nephritis.=--A single case of nephritis successfully treated by -blood transfusion has been recorded by Ramsay. The patient, a man -aged 22, had been ill for ten days. He was slightly drowsy and had a -furred tongue. His systolic blood pressure was 100 mm. and diastolic -60. His urine had a specific gravity of 1010, and contained much -albumin and many granular casts, but no blood cells. Vomiting was -incessant. On the second day after admission he passed 2 ozs. of -urine and his systolic blood pressure fell to 90 mm., his diastolic -to 40 mm. His low blood pressure and the evident imminence of -suppression of urine suggested the administration of blood; he was -accordingly given 1,140 cc. of fresh blood. His blood pressure -immediately rose to 100 mm. systolic, and 50 mm. diastolic, and -the other symptoms abated. He passed 24 ozs. of urine during the -ensuing twenty-four hours. He was afterwards treated with alkalies, -intravenously and by the mouth, and his condition steadily improved. -It cannot be inferred from the evidence that his recovery is to be -attributed entirely to the transfusion, but it appears to have been -initiated by this treatment, which was a reasonable one in view of -the symptoms. No other similar cases have as yet been recorded. - - -=Carbon Monoxide Poisoning.=--In any condition in which the function -of a large proportion of the red blood cells as oxygen carriers -has been temporarily destroyed or impaired, it is a rational -procedure to replace as many of them as possible with normal red -cells. The evidence that transfused blood cells can carry out their -functions in their new host has been given on another page. In -carbon monoxide poisoning the oxyhæmoglobin has been converted into -carboxyhæmoglobin, which is more stable than the oxygen compound, and -therefore useless for purposes of respiratory exchange. Undoubtedly -the ideal treatment for carbon monoxide poisoning is by putting the -patient in a specially constructed chamber in which he can breathe -oxygen under a pressure of about three atmospheres. By this means -the carboxyhæmoglobin is dissociated and replaced by oxyhæmoglobin. -An oxygen chamber is usually not available, though a very useful -substitute may be tried in the shape of a Haldane’s oxygen mask. -Failing this, there is evidence to show that a blood transfusion is -an effective form of treatment. Nevertheless, although poisoning with -coal gas is by no means a rare event, this treatment does not seem -to have had the attention it undoubtedly deserves. Transfusion was -first used for carbon monoxide poisoning by Hüter in 1870, who was -able to record a case in which recovery appeared to have been due to -the treatment. It was also advocated by Lauder Brunton in 1873. After -this date recorded cases are few, but in 1916 Burmeister put this -form of treatment on a more scientific basis by direct experiment. -Using rabbits and dogs he showed that if the animals treated with -coal gas were transfused without a venesection, 75 per cent. of them -recovered. Of a series of control animals, which were not transfused, -nearly all died. - -Most writers on the subject have recommended that as much blood -be taken from the patient by venesection as is to be replaced by -transfusion. On theoretical grounds this seems to be sound, though -it is not supported by the results of Burmeister’s experiments. -Nevertheless, in a recent series of seven cases reported by Bruce -Robertson, in which 1,000 cc. of blood were removed and the same -amount given by transfusion, satisfactory results were obtained. If -no venesection is done, there is some risk that the transfusion may -put an additional load upon an already over-strained right heart, -so that a preliminary venesection is certainly a wise precaution. -Transfusion should not be withheld until the patient is _in -extremis_; if no oxygen chamber is available, it should be given -at once. A minimum amount of 750 cc. of blood should be taken by -venesection, and 1,000 cc. of blood should be given. If the patient’s -condition does not then show enough improvement, this should be -repeated. - - -=Nitrobenzol and Benzol Poisoning.=--Blood transfusion for poisoning -with nitro-benzol (C_{6}H_{5}NO_{2}) has been recommended by -Hindse-Nielsen, who records a case in which it was successfully -employed. The patient, a girl of 19, had taken a tablespoonful of -the poison several hours before, and her condition appeared to be -hopeless. She was deeply cyanosed, the mucous membranes being of a -dark blue colour. Washing out the stomach and inhalation of oxygen -were tried without effect. Finally she was bled to the extent of -600 cc., and 1,000 cc. of citrated blood were injected. Her colour -at once became more normal and recovery followed. The literature -does not contain records of any other cases treated in this way, -but the condition is analogous to coal-gas poisoning referred to in -the last paragraph, oxyhæmoglobin being in this case replaced by -methhæmoglobin, and its treatment by transfusion has, therefore, a -rational basis. - -A somewhat similar condition is seen in benzol poisoning, though -there is an additional destruction of red blood cells. Three cases -treated by transfusion have been reported by McClure. One patient, -whose red blood cells had been reduced to 1,460,000 per cmm., was -extremely ill, but recovered after five transfusions up to a total -amount of 1,500 cc. - - -=Diabetes.=--Blood transfusion has been used in treating diabetes -mellitus, but there is no evidence to show that it is of any service. -Ottenberg and Libmann transfused four patients who were already in -diabetic coma, but no improvement resulted. Another patient who was -transfused by Raulston was actually made worse, as was indicated by -an increased output of sugar, acetone, and ammonia compounds. - - -=Pellagra.=--The precise ætiology of pellagra being still unknown, -treatment of the disease can only be empirical. From this point of -view blood transfusion has been tried by Cole, who began using it -in 1908. The results in twenty cases have been reported, and are -distinctly encouraging. All the transfused patients were in the -last stages of the disease, but nevertheless a recovery rate of 60 -per cent. was obtained, the usual rate being 10 to 20 per cent. In -the present state of knowledge comment is scarcely possible, but -if pellagra is, as some observers have suggested, a “deficiency -disease,” it may be supposed that the transfused blood provides a -temporary supply of the substance that is lacking; the patient is -thus enabled to start along the road to recovery. - - - - -CHAPTER IV - -DANGERS OF BLOOD TRANSFUSION - - -Appreciation of the dangers attending the practice of blood -transfusion has varied greatly at different times. In the seventeenth -century a happy ignorance took no account of them whatever. In the -eighteenth century they were so greatly feared that transfusion fell -into abeyance. In the nineteenth century it was realized that dangers -existed, but they were imperfectly understood; when fatalities -occurred, a partial knowledge explained them away more easily than -our fuller knowledge can to-day, so that transfusion was practised in -spite of them. At the beginning of the twentieth century, with the -discovery of “blood groups,” it was thought that all danger had been -eliminated. At the present time the pendulum is swinging back again, -and the problem of the complete elimination of danger is proving more -complex than it was thought to be a few years ago. - -The chief dangers of blood transfusion are two-fold--that of -introducing into the recipient a disease carried by the donor, and -that due to the inherent properties of the donor’s blood which may -interact in a serious manner with the blood of the recipient. The -first of these dangers is obvious, and common sense will suggest what -steps should be taken to avoid it. Danger of communicating disease -is almost restricted to conditions in which an infective agent is -actually circulating in some form in the blood. Inquiry will usually -be enough to establish the possible presence in the prospective -donor’s blood of an organism such as the malaria parasite. -Nevertheless, a case has been recorded by van Dijk, in which malaria -was transmitted by injecting into a patient suffering from influenza -some serum obtained from another patient who was supposed to be -convalescent from influenza, but had been treated for malaria a few -months earlier. Another case is reported by Bernheim, who transmitted -a double infection of malaria--tertian and æstivo-autumnal--by means -of a blood transfusion. Blood infections, such as those due to the -exanthemata, may be avoided by the precaution of never employing a -blood donor who shows any signs of present illness, even though a -raised temperature be the only symptom. In certain cases, when, for -instance, the prospective donor may be suffering from tuberculosis in -some form or from gonorrhœa, the organism is extremely unlikely to be -present in the blood in numbers sufficient to communicate disease. -Nevertheless, on general principles, such donors should be eliminated -if circumstances permit. The most subtle form of infection, the most -dangerous, and the most difficult to eliminate, is syphilis. Definite -cases have been recorded in which syphilis has been communicated by -blood transfusion. In one instance recorded by Sydenstricker and -by Bernheim a father was infected by blood taken from his son, who -had refused beforehand to allow himself to be tested. Fortunately -such occurrences are rare. Still rarer and still more curious is the -transmission of horse asthma recorded by Ramirez. In this instance, -in which the disease is to be regarded as a form of anaphylaxis, the -patient had received an amount of serum sensitive to horse protein -great enough to provide him with the corresponding symptoms for some -time afterwards. - -If the transfusion is being done at leisure, the donor’s blood -must be tested for a positive Wassermann reaction. Even this test, -however, has been known to fail, and since, in an emergency, the -most careful inquiry, aided by a desire on the part of the donor to -arrive at the truth, may reach an erroneous conclusion, the risk of -infection with syphilis can never be completely eliminated. Since -reasonable care can make the danger a remote one, it need not hinder -the performance of a transfusion any more than an occasional death -under anæsthesia prevents the frequent use of general anæsthetics. -The mere existence of such a danger is, however, an argument in -favour of the general use of the “professional blood donor,” whose -Wassermann reaction, personal history, and mode of life are well -known to the practitioner; the previous use of his blood on perhaps -more than one occasion, if unattended by any ill results, will give -an added confidence. The tragedy of such a misfortune is so great -that no precaution which can possibly be taken should be regarded as -absurd. - -The second danger present in the inherent qualities of the donor’s -blood has been already alluded to in the historical sketch of the -subject. Before the existence of the “blood groups” was realized, a -number of fatalities due to an unexplained cause had occurred. Even -after the existence of the groups had been demonstrated, the warning -that resulted was apt to be disregarded, and it was not until still -further fatalities due to this incompatibility of bloods had taken -place that the very important nature of the discovery came to be -understood. The chances are, on the whole, that the blood of any -donor chosen at random will not prove fatal to a given recipient; -nevertheless, it must frequently happen that the transfusion -without being fatal will be wasted, or to some degree detrimental. -It is therefore evident that the existence of blood groups must be -seriously regarded, and it is necessary to enter into a detailed -consideration of their relations to one another and the symptoms -which they may produce. In the next chapters will be found a further -description of their physiology and pathology and of the methods of -testing for them. - -It has long been known that if the blood of one species of animal -is injected into the circulation of another species, the corpuscles -of the foreign blood are at once destroyed, their contained -hæmoglobin being set free. This process of hæmolysis is under such -circumstances rapid and complete, and hæmoglobin may appear in the -urine in a short time. The precise nature of the reaction is obscure -and need not be discussed here in detail. The present bearing of -the phenomenon is the fact that a similar, or analogous, reaction -may occur when the bloods of certain individuals are mixed with -the bloods of certain others even of the same species. It was the -observation of this fact that first led to the discovery of the -so-called “blood groups” among human beings, and so to the partial -elucidation of the cause of the previously unexplained fatalities -following blood transfusion. In 1901 Landsteiner had detected the -presence of hæmolysins and iso-hæmolysins in blood and classified -three groups in human beings. In 1907 it was shown by Jansky that -human beings may be divided into four groups, the blood of the -members of each group having a certain definite relation to the blood -of the other groups as determined by the manner of their interaction. -The work was repeated and confirmed by Moss in 1910. The reaction -takes place between the serum of one group and the corpuscles of the -other groups, and is evidenced by the agglutination or hæmolysis -of the corpuscles that are being acted upon. In the course of his -researches Moss showed that hæmolysis, or the breaking up of the -corpuscles, is always preceded by agglutination or the clumping -together of the corpuscles. The process does not necessarily go as -far as the destruction of the corpuscles, but may be arrested at the -stage of agglutination. It may, on the other hand, be as rapid and -complete as if the bloods belonged to different species, and the -appearance of hæmoglobin in the urine may quickly give evidence of -this. - -The groups have been arbitrarily numbered, and it is now usual to -refer to them by the Roman numerals I, II, III, and IV. According to -the accepted convention, the reactions of these four groups are as -follows:[5] - -The corpuscles of Group I are agglutinated by the sera of II, III, -IV. The corpuscles of Group II are agglutinated by the sera of III, -IV. The corpuscles of Group III are agglutinated by the sera of II, -IV. The corpuscles of Group IV are not agglutinated by any of the -other groups. - -On the other hand: - -The serum of Group I agglutinates no other corpuscles. The serum of -Group II agglutinates the corpuscles of Groups I, III. The serum of -Group III agglutinates the corpuscles of Groups I, II. The serum of -Group IV agglutinates the corpuscles of Groups I, II, III. - -This may be represented more graphically by the following table, a + -indicating agglutination, a - indicating no reaction: - - -------------------+-----------------------+ - | Serum | - +-----------------------+ - | I | II | III | IV | - ------------+------+-----+-----+-----+-----+ - Corpuscles | I | - | + | + | + | - +------+-----+-----+-----+-----+ - | II | - | - | + | + | - +------+-----+-----+-----+-----+ - | III | - | + | - | + | - +------+-----+-----+-----+-----+ - | IV | - | - | - | - | - ------------+------+-----+-----+-----+-----+ - -The active principle in the serum is called “agglutinin” or -“hæmolysin,” according to the degree of the reaction, and the -corpuscles are rendered sensitive to this by the possession of -an “iso-agglutinin” or “iso-hæmolysin.” Sometimes the corpuscles -are said to have “agglutinophilic” properties. It may be stated, -therefore, that the serum of Group I entirely lacks agglutinins, -whereas the corpuscles of Group IV lack iso-agglutinins. All these -terms, like the “amboceptors,” “receptors,” and “haptophores” of -Ehrlich, are used to conceal ignorance rather than as an expression -of knowledge, but, until more light has been shed upon the nature of -the reactions, ignorance must be abbreviated. - -It is now clear that the blood as a whole contains two sets of -reactions which are independent. These properties reside in the -serum and in the corpuscles respectively, and the reactions are -complementary between Groups II and III, that is to say, the serum of -each group agglutinates the corpuscles of the other. It will be seen -from the table that the serum of Group I blood does not agglutinate -the corpuscles of any of the other groups, and conversely the -corpuscles of Group IV are not agglutinated by the serum of any of -the other groups. Individuals of Groups I and IV have therefore been -named “universal recipients” and “universal donors” respectively. -This implies that if the recipient be found to belong to Group I, -the blood of any donor may be transfused into his veins irrespective -of his group, and that if the donor be of Group IV, his blood may -be used for transfusion irrespective of the group of the recipient. -These statements may be accepted as true in an emergency, but -important reservations may have to be made under certain conditions. - -It was at one time believed that the group reactions were clear-cut -and absolute rather than relative. At the present time, however, -the view is gaining ground that there may be some “over-lapping” of -groups, that is to say, a serum may contain agglutinins which give a -gross reaction with the corpuscles of one group and a reaction with -another group so slight that it can be detected only with difficulty, -or alternatively the recipient’s corpuscles may give a definite and -limited group reaction, while his serum may cause some agglutination -in the blood of a theoretically compatible group. These properties -have recently been termed “major” and “minor agglutinins” by Unger, -who claims that the possible presence of minor agglutinins makes it -advisable to test the recipient’s blood directly against the donor’s -in every case. The term “universal donor” commonly applied to Group -IV is, in fact, misleading. The blood of Group IV cannot be used -indiscriminately with complete impunity. The groups are determined by -the major agglutinins, and by these the ordinary gross reactions may -be eliminated. Everyone who has used blood transfusions extensively -has observed that slight reactions may occur after transfusion with a -compatible blood, irrespective of the methods employed. Usually these -reactions are slight, and do not in any way prejudice the benefits -conferred by the transfusion, but they may become greatly accentuated -in the later transfusions of a series, and it is probable that minor -agglutinins may be developed in certain pathological conditions. -Further reference to these phenomena will be made elsewhere (p. 93). -In addition to this, it has been commonly observed that the intensity -of the reaction varies greatly with the sera of different individuals -of the same group. It has also been stated by Stansfeld that the -agglutinating power of the serum of an individual may vary from time -to time. As a rule the corpuscles of a person belonging to Group I -are not agglutinated with equal rapidity or intensity by the sera of -Groups II and III, but the meaning of this phenomenon has not been -fully investigated. - -A possible source of trouble will occur to anyone looking -critically at the table of reactions, for it will be noticed -that the serum of Group IV, the so-called “universal donors,” -agglutinates the corpuscles of all the other groups. How does it -come about, therefore, that the blood of this group may be given -indiscriminately? The answer is to be found in the fact that though -the reaction takes place as shown in the table _outside the body_, -nevertheless the serum of the transfused blood does not exert its -agglutinating power in the body of the recipient. Several hypotheses -have been advanced to account for this discrepancy, though no -final explanation has yet been arrived at. In the first place it -is possible that the agglutinating power of the serum is rendered -ineffective by the dilution which it undergoes when it is mixed with -the blood of the recipient. It has been shown, however, by Culpepper -that agglutination takes place outside the body with serum diluted up -to 1 : 150, a degree of dilution far greater than is ever obtained -in a transfusion where the dilution in the patient’s circulation -is usually no greater than 1 : 7. Secondly, it has been suggested -that the transfused plasma meets with an excess of plasma containing -protective or antihæmolytic properties. The evidence on this point -is conflicting. Hektoen in 1907 was unable to demonstrate any such -property in serum or plasma. Brem and Minot in 1916 both claimed -to have demonstrated antihæmolytic properties in serum, and Minot -added the observation that its concentration varies. Karsner in 1921 -reported that he had failed to demonstrate anti-agglutinins in the -blood. For the present, therefore, the point must remain undecided. -Finally, it is possible that the agglutinins of the transfused -plasma, meeting with an excess of agglutinable cells, are all -absorbed without actually producing any agglutination. Whichever of -these hypotheses be true, the fact remains that the blood of Group -IV individuals may be given without serious effects in most ordinary -cases in which transfusion is indicated. - -It must not be inferred from the tabulated reactions that a -transfusion with the blood of an incompatible group necessarily -produces a fatal, or even a serious, result. If, for instance, -an individual of Group II be transfused with blood of Group III, -the corpuscles of the donor’s blood will certainly be rendered -ineffective, being destroyed either at once or in the course of a -short time. But beyond this wastage of the transfused blood there -may be no effects as shown by morbid symptoms in the recipient; he -will merely not be benefited. There may, on the other hand, be an -evident reaction in the recipient, the symptoms varying from slight -discomfort to almost immediate death. It appears, therefore, that -there is a gradation of toxicity between the bloods of incompatible -groups, so that it may be justifiable owing to extreme urgency in -certain cases to perform a transfusion without doing any preliminary -tests on the bloods of donor and recipient. There is a good -chance that the groups will be compatible; if, however, they be -incompatible, there is still a good chance that the recipient will be -no worse off than he was before the transfusion. - -Even when the tests have been performed, it may still happen -that through various causes a mistake has arisen. Owing to the -inexperience of the operator or to staleness of the sera used -in performing the test, an incompatible group may appear to be -compatible. It is necessary, therefore, that everyone who performs a -transfusion should be able to recognize the symptoms of a reaction -as soon as it begins to appear, so that the transfusion may be at -once discontinued. Sometimes the reaction between incompatible -groups is so immediate and severe that death takes place almost at -once. I did not myself perform any transfusions until after the -period when blood-grouping tests had become a routine procedure, so -that I have no personal experience of such unfortunate results. The -symptoms may therefore best be described in the words of one who -has several times witnessed the effects of an incompatible blood: -“The clinical picture of these reactions is typical. They occur -early, after the introduction of 50 cc. or 100 cc. of blood; the -patient first complains of tingling pains shooting over the body, a -fullness in the head, an oppressive feeling about the precordium, -and, later, excruciating pain localized in the lumbar region. Slowly -but perceptibly the face becomes suffused a dark red to a cyanotic -hue; respirations become somewhat laboured, and the pulse rate, -at first slow, sometimes suddenly drops as many as from twenty to -thirty beats a minute. The patient may lose consciousness for a few -minutes. In one-half of our cases an urticarial eruption, generalized -over the body, or limited to the face, appeared with these symptoms. -Later the pulse may become very rapid and thready; the skin becomes -cold and clammy, and the patient’s condition is indeed grave. In -from fifteen minutes to an hour a chill occurs, followed by high -fever, a temperature of 103° to 105°, and the patient may become -delirious. Jaundice may appear later. The macroscopic appearance of -hæmoglobinuria is almost constant.” (Peterson.) - -In a fatal case recorded by other writers the chief symptom was -hæmoglobinuria, which progressively increased until the functions of -the kidney became so much interfered with by deposits of hæmoglobin -or damaged corpuscles that the patient died with suppression of urine -and all the signs of uræmia (25). - -In other cases a slighter and transient hæmoglobinuria has been -noticed, showing that some destruction of red cells has taken place -without producing any further effects. This symptom is, of course, -due to hæmolysis following reactions between the serum and corpuscles -as explained above. The variation in degree of the reaction is to be -partly explained by the fact that there are three possibilities: (1) -The donor’s corpuscles may be hæmolysed by the recipient’s serum; -this will result in the transient hæmoglobinuria and wastage of the -transfused blood; (2) the recipient’s corpuscles may be hæmolysed -by the donor’s serum, or (3) serum of each may hæmolyse the other’s -corpuscles. Either of the latter events will be extremely serious. -As already mentioned, hæmolysis is always preceded by agglutination, -and it seems that the agglutination may be the more rapidly fatal of -the two. It was probably this that was chiefly responsible for the -suppression of urine in the case referred to, and a case has been -recorded in which it appeared to be the only cause of immediate death -or, as an American writer expresses it, “sudden exitus took out, out -of a clear sky,” owing to the presence of multiple emboli. - -In addition to the evidence of hæmolysis the patient may exhibit -the symptoms described above. Sometimes the urticarial rash has -been accompanied by vomiting and headache. This group of symptoms -suggests that the condition is analogous to the anaphylactic shock -which may follow the intravenous injection of any foreign protein. -The symptoms in a mild degree do occasionally follow the transfusion -of blood which has been shown to belong to a compatible group, and it -had been found to develop even to an alarming extent after the later -transfusions, when a series was being given for a condition such -as pernicious anæmia (34). In such cases, however, as is suggested -elsewhere, this may, perhaps, be regarded as true anaphylactic shock. -The symptoms which may accompany a first transfusion cannot be -identical with this since true anaphylaxis must have been preceded by -sensitization with a minimal dose of foreign protein introduced into -the circulation. - -It was formerly thought that possibly the products of hæmolysis were -themselves toxic and capable of producing the symptoms described. -This seems, however, to have been disproved by Bayliss, who has shown -that in the dog and cat the hæmolysed blood of the same species is, -with extremely rare exceptions, innocuous. - -Another possible cause of similar symptoms is the sodium citrate used -as an anticoagulant in one of the methods of transfusion subsequently -to be described. But the symptoms, if due to this cause, will not be -accompanied by any signs of hæmolysis, are usually not severe, and -are always very transient. This will be referred to again later on. - -The symptoms of incompatibility begin to be apparent so quickly that -the worst results can be avoided by the exercise of caution. If for -any reason it has been necessary to use an untested blood donor, the -first 100 cc. of blood should be injected very slowly. If no untoward -symptoms result, the remainder of the blood can be injected with -greater confidence. Little can be said as to the treatment of this -condition, for prevention is far better than cure. When the symptoms -have developed, the damage has been done, and cannot be undone. The -ordinary measures for combating severe collapse may be used. - -A lesser danger of transfusion is that of administering the blood -too rapidly. Sometimes during a transfusion the patient complains of -difficulty in breathing and a sensation of tightness in the chest; -this should always be regarded as a warning that the blood must be -given more slowly or perhaps that enough has been given and that -the transfusion should be discontinued. Usually the symptom amounts -to nothing more than discomfort, and will disappear if caution be -exercised. The explanation is to be found in the too rapid filling -of the venous side of an impaired circulation with overloading, and -perhaps temporary dilatation, of the right side of the heart. I have -never seen these symptoms occur to an alarming degree, but actual -loss of consciousness with a very rapid and feeble pulse has been -recorded by other writers. Directions as to the amount of blood which -should be given and the rate at which it should be injected so that -these symptoms may be avoided will be found under the description of -methods given in a later chapter. - - - - -CHAPTER V - -PHYSIOLOGY AND PATHOLOGY OF BLOOD GROUPS - - -In the foregoing chapter the reactions between the blood groups and -the morbid symptoms which may follow the injection of incompatible -blood have been described. In the present chapter some account will -be given of the more general physiology and pathology of the groups. - -It seems to be clear that iso-agglutinins and iso-hæmolysins, that is -to say, serum reactions among the individuals of a species, are to be -found distributed widely through the animal kingdom. The phenomenon -is, however, weak in operation compared with that found among human -beings, and it is very much more difficult to demonstrate. The facts -have not been investigated for very many species of animals. - -Some of the earliest attempts to investigate the distribution of -iso-agglutinins among animals were made by Hektoen in 1907. He tested -the blood of rabbits, guinea-pigs, dogs, horses, and cattle; his -results were negative in every case, but probably his technique was -imperfect or an insufficient number of animals was tested. Grouping -has been found among goats by Ehrlich. Ottenberg and others believe -that they have demonstrated the existence of three groups among -steers, and of four groups among rabbits. Von Dungern has shown -that there are four groups among dogs. Agglutination reactions were -found by Ingebrigtsen and by Ottenberg among cats, but they were -not constant, and it was not found possible to distinguish any -grouping. The same was found to be true of rats. I have not been -able to discover any record of research upon iso-agglutinins in -birds or reptiles. The phenomenon of blood groups has a possible -bearing on the success or failure of experimental transplantations -of tissue, whether healthy or diseased, from one animal to another -of the same species. From this point of view an investigation of -the blood reactions among mice was carried out by B. R. G. Russell -in the laboratories of the Imperial Cancer Research Fund, but he -was unable to find any sort of grouping. Ingebrigtsen has made an -attempt to correlate the results of the transplantation of arteries -in cats with their serum reactions, but he was unable to do so. His -results were equally bad whether iso-agglutinins were present or -not. Nevertheless, it is highly probable that the success of tissue -transplantation in man will be found to be largely dependent upon -compatibility of blood groups in donor and recipient. The problem -is one that cannot easily be investigated by experiment on animals, -among which natural incompatibility is evidently much less well -marked than it is in man. A method of overcoming this unsuitability -is suggested by the experiments of Ottenberg and Thalimer. These -observers, as already mentioned, found that in cats iso-agglutinins -were present, though inconstant; on the other hand, iso-hæmolysins -were seldom if ever found in normal cats, though they often -appeared in the recipients of transfusions. Grafting experiments -might therefore be preceded by transfusions designed to stimulate -artificially incompatibility of the tissue fluids. - -The incompatibility of blood is essentially a phenomenon which -distinguishes different _species_ of animals, since in no case can -the blood of one species circulate unaltered in the blood-vessels of -another kind of animal. This serological specificity may be in some -way related to the sterility of one kind of animal with another, -though not actually causing it, and so be merely an incidental -phenomenon. It cannot be in any sense protective, since it never -happens in the course of nature that blood is transferred from one -animal to another. In the same way it is difficult to see how there -can be any biological “purpose” in similar differences between -individuals of the same species, and, so far as is at present known, -the possession of a particular group does not confer upon its owner -any advantage over the individuals of other groups, such as a -relatively greater immunity from disease, longevity, or fertility. It -is quite clear that there is no connexion between incompatible blood -groups and sterility between individuals. - -An investigation of a possible relation between blood groups and -disease has been begun by W. Alexander at St. Andrews University. In -a preliminary communication concerning the blood groups found among -fifty patients suffering from “malignant disease” of all forms, -including leukæmia, he has found that there is a considerably higher -proportion of Groups I and III than among healthy people. On the -other hand, the groups are found in the normal proportions among -people suffering from tuberculosis, syphilis, and tetanus. It would, -however, be premature to assume that individuals of Groups I and -III are more liable to suffer from “malignant disease” than other -people, as the numbers tested are, at present, too small for definite -conclusions to be formulated. Also it remains to be proved that the -presence of malignant disease does not produce an alteration in the -agglutinating reactions by which the groups are determined. - -It seems probable that the differences between the groups have arisen -incidentally in the evolution of mankind, possibly as the result of -the parallel descent of two or more original stocks from different -sources, which afterwards converged and mingled, with the production -of serological hybrids. In view of this it is of interest to find -that some investigation of the racial incidence of blood groups has -already been carried out. On the Macedonian front during the war a -large number of men of many different races were gathered together, -and scientific advantage of this opportunity was taken by L. and H. -Hirschfeld. The blood groups were determined in approximately 8,000 -individuals, including French, English, Italians, Germans, Austrians, -Serbs, Greeks, Bulgarians, Arabs, Turks, Russians, Jews, Malagasies, -Senegal Negroes, Annamese, and Indians. According to the results -obtained by the Hirschfelds, the groups designated II and III show -a definite variation in their distribution among different races. -As will be seen hereafter, Group I is compounded of the two factors -producing Groups II and III, while Group IV results from their -absence. It is therefore necessary only to consider the incidence -of Groups II and III in calculating the racial differences. For the -statistical tables and diagrams the reader must be referred to the -original paper published in 1919, but the results may be roughly -summarized as follows. It was found that the factor producing Group -II is prevalent among European peoples, whereas the factor producing -Group III is characteristic of men from Asia and Africa. Thus the -Group II factor was found in not less than 45 per cent. among most -European peoples. It gradually diminishes in the countries lying -between Asia and Central Europe, being present in Arabs 37 per cent., -in Russians 37 per cent., in Jews 38 per cent. In Asiatics and -Africans it falls considerably, being in Malagasies 30 per cent., -in Negroes 27 per cent., in Annamese 29 per cent., in Indians 27 -per cent. On the other hand, the factor producing Group III shows -exactly the opposite variation. Among the English, the most Western -people of Europe, it is rare, being found by these observers to be -present in only 10 per cent.; it rises to 14 per cent. in French and -Italians, to 18 per cent. in German Austrians, and to 20 per cent. -in the Balkan peoples. In Africa and Asia the Group III factor rises -considerably, being present in Malagasies 28 per cent., in Negroes 34 -per cent., in Annamese 35 per cent., and in Indians 49 per cent. - -We may still be far from elucidating the anthropological meaning -of these facts, for the mingling of the hypothetical stocks of -which mankind is made no doubt began in a remote antiquity, and -it is possible that a serologically pure race does not exist. The -investigation, however, of the more isolated peoples might throw much -light on the problems of anthropology. - -Interesting as the wider questions may be, we are here more -immediately concerned with the distribution of the blood groups -amongst our own population. The percentages in which the four groups -occur have been estimated by various observers, and, as will be -readily understood from the foregoing remarks, the numbers show some -variation. The approximate figures as worked out by three observers -in America are as follows: - - ------+----------+---------------+---------------- - | Bernheim | Moss | Culpepper - | | (1,600 tests) | (5,000 tests) - ------+----------+---------------+---------------- - I | 2 | 10 | 3 per cent. - II | 40 | 40 | 38 ” ” - III | 15 | 7 | 18 ” ” - IV | 43 | 43 | 41 ” ” - ------+----------+---------------+---------------- - -The percentages found among the first hundred men whom I tested in -the British Army in 1917 conformed almost exactly to the first of -these series of figures, and they may be taken as an average result -for Western peoples. It will now be seen upon what grounds it was -stated in the last chapter that the chances were in favour of the -blood of a donor chosen at random being compatible with that of the -recipient. If the patient belong to Group II, then 83 per cent. of -other bloods will be compatible. If he belong to Group III, 58 per -cent. will be compatible. Only if he belong to Group IV will the -chance in favour of compatibility fall below 50 per cent. - -This statement of the facts concerning distribution of the blood -groups will serve to emphasize the absolute necessity for the careful -testing of a donor before his blood is used for transfusion. But, -further than this, it is necessary to clear away several widely -spread misapprehensions as to the group relations between an infant -and its mother and between the various members of a family. It has -several times been stated in print that a mother’s blood must be -compatible with that of her child, or sometimes that a baby has no -blood group, so that it may be safely transfused with blood taken -from its mother or its father without preliminary testing. On other -occasions the statement has been made that the brother or sister of -a patient is more likely than other people to belong to the same or -a compatible blood group, so that untested blood may be transfused -from one member of a family to another with little risk. Knowledge of -the existence of blood groups has become somehow mixed up with vague -popular beliefs concerning “affinities” and “blood relations.” Such -confusions must, however, be dissipated, for none of these statements -are more than partially true, and they may lead to a false sense of -security and to disaster. - -The assertion that an infant has no blood group was tested by the -writer some time ago and shown to be false. On several occasions -a newly born infant was tested and found to show well-marked -agglutination reactions indicating Groups II or III as the case -might be. Even in 1905 it had been shown by Martin that reactions -could often be demonstrated between an infant’s corpuscles and the -maternal serum, and sometimes between the infant’s serum and the -maternal corpuscles. More recently (March 1920) the results of a full -investigation into the reactions found in infants and children have -been published by W. M. Happ in America. These researches began with -the testing of blood from the umbilical cord, and this was seldom -found to show the blood reactions as given by the adult. So far the -statement quoted above was justified. It is even true that the serum -of an infant’s blood will usually not give any reaction at birth -or during the first month. The percentage in which it does give a -reaction increases with the age of the child; after one year it is -usually, and after two years always, established. On the other hand, -the agglutination reaction in the corpuscles appears before that in -the serum, so that the grouping tested in this way may be present -immediately after birth, as I found to be the case. It is possible -that the grouping which first appears may afterwards be modified, but -any change which occurs is always by the addition of factors and not -by their subtraction; thus an apparent Group IV may become a Group -II or III, or an apparent Group II or III may become a Group I. It -is found that when a reaction is present in both the corpuscles and -the serum, the group does not afterwards change. Happ’s conclusion, -based on his investigations, was that it is unsafe to transfuse an -infant with its mother’s blood without first making the usual tests, -and the reasons for this will now be evident. In the first place an -infant _may_ be possessed of its final blood reactions very shortly -after birth, and should therefore be treated in the same way as if -it were an adult. In the second place, although its serum may be -without agglutinating powers, so that transfused corpuscles will -not be attacked, yet its corpuscles may be possessed of pronounced -agglutinophilic properties, so that they may be seriously affected -by the serum of transfused blood from an incompatible group. In -the third place, as will presently be seen, it is by no means the -rule that an infant should belong to the same group as its mother, -whatever its blood reactions may be. - -Another set of observations, leading to precisely the same -conclusions, have been made by F. B. Chavasse of Liverpool. He terms -the potential agglutination of the fœtal corpuscles by the mother’s -serum, and of the maternal corpuscles by the serum of the fœtus, the -“maternal threat” and the “fœtal threat” respectively, and states -that there is no obvious relationship between the “fœtal threat” and -eclampsia or the toxæmias of pregnancy. The inference is therefore -justified that there is no transference of the agglutinating -substances in either direction across the placental membranes. No -chemical “immunity” is acquired, therefore, on either side, since -the protection is mechanical. This agrees with the fact observed -by Happ that the mother’s milk contains the same agglutinins as the -serum of her blood; but these do not have any deleterious effect -upon the infant, and are therefore either not absorbed at all or are -destroyed in the process of digestion. - -The statement that the blood group of an infant is not necessarily -the same as that of its mother can be amplified, for it has been -found that blood groups are inherited on a definite plan, so that if -the groups of the parents be known, certain predictions can be made -as to the possible groups that may be found among their offspring. -Many characters in animals and plants have been shown during the last -twenty years to be transmitted according to the Mendelian plan of -inheritance, but up to the present time very few normal characters in -man have been isolated, and their manner of inheritance demonstrated, -though a number of pathological conditions have been shown to conform -to the theory. It is therefore of much interest to find that the -inheritance of blood groups in man can be quite satisfactorily and -consistently explained in Mendelian terms. - -According to this theory, each quality in an organism which can be -isolated and investigated independently of other qualities, is termed -a “unit character,” and the appearance of each such unit character -is determined by the presence of something called a “factor” in the -sexual cells or “gametes,” male and female, by the union of which the -individual is formed. Further, these unit characters are believed to -occur in alternative pairs, and at first it was supposed that each -alternative pair consisted of “dominant” and “recessive” characters, -the second of which could only make its presence apparent in the -individual if the dominant character were absent. Subsequently -it was seen that the dominant and recessive characters need not -necessarily consist of two positive, though opposite, qualities, -but might better be regarded as consisting of the presence of a -character and its absence. To use a classical illustration of this -view, sweet peas may be classified into tall peas and dwarf peas. At -first the unit characters were taken to be tallness (dominant) and -dwarfness (recessive). Later this idea was modified, and it was said -that potentially all peas are dwarf, but to some is added a factor -producing tallness, this factor being absent in those that are dwarf. -To represent this idea more simply a conventional notation has been -used, according to which the large letters of the alphabet indicate -the presence, and the small letters the absence, of each factor. - -In order to apply this theory to the case under consideration, it has -been suggested that two pairs of factors are concerned: - - A the _presence_ of the character producing Group II. - - a the _absence_ of the character producing Group II. - - B the _presence_ of the character producing Group III. - - b the _absence_ of the character producing Group III. - -Each pair of factors is transmitted independently of the other. Both -A and B may be absent, in which case the individual belongs to Group -IV; or both may be present, and in this case the individual gives the -reactions of Group I. - -It must be understood that the term “character producing Group II” -is here used as a convenient way of expressing the obscure and -probably complicated set of properties responsible for the reactions -manifested by individuals of Group II. It includes not only the -agglutinin or hæmolysin of the serum which reacts with corpuscles of -Group III, but also the complementary iso-agglutinin or iso-hæmolysin -by virtue of which the corpuscles react with serum of Group III. - -The appearance of the different groups can now be further explained -in terms of the Mendelian theory. According to the conception of the -individual formulated by Mendel, each cell of the body contains an -ingredient derived from each of the sexual cells or gametes which -united at the moment of fertilization of the ovum by the spermatozoon -to form the individual. But when the adult in his or her turn forms -sexual cells or gametes, these ingredients separate again, half the -gametes containing one of the pair of factors, half containing the -other. This process certainly takes place during the rearrangement -of the nuclear substance or chromosomes at the cell divisions which -result in the formation of the ripe sexual cells. It is called the -“segregation of the gametes.” - -In the present case the unit character producing Group II will be -first considered. As already explained, the factors concerned may be -called A and a, and the individual of Group II may be constituted by -AA or Aa, and the gametes, therefore, may contain either A or a, but -not both. The individuals resulting from the union of the gametes -derived from Aa adults may then be constituted in three ways--AA, -Aa, or aa. Similarly for the unit character producing Group III, -the factors concerned may be called B and b, and the individual of -this group may contain BB or Bb. The gametes then contain either B -or b, and the individual resulting from their union may again be -constituted in three ways--BB, Bb, or bb. - -In computing the results, however, it must be remembered that most, -or perhaps all, people are hybrids, so that both unit characters -are present simultaneously, and all the factors must be taken into -account. It is easily seen that the gametes derived from a hybrid -individual must contain one of the following combinations: - - AB, Ab, aB, or ab, - -and consequently the individuals formed from them must have one of -the following constitutions: - - AB--Ab, Ab--aB, aB--ab, ab--ab, AB--AB, - AB--aB, Ab--ab, aB--aB, - AB--ab, Ab--Ab. - -This includes all the possible combinations that can result from the -chance union of the gametes, and it is now clear which blood groups -result from which combinations, if it be remembered that - - A is dominant to a, - B ” ” ” b, - -and that - - Group I results from the _presence_ of both A and B. - ” II ” ” ” ” ” A only. - ” III ” ” ” ” ” B ” - ” IV ” ” ” _absence_ ” both A and B. - - Thus Group I may be constituted by AB--AB. - AB--aB. - AB--Ab. - AB--ab. - Ab--aB. - Group II may be constituted by Ab--Ab. - Ab--ab. - ” III ” ” ” ” ab--aB. - aB--aB. - ” IV ” ” ” ” ab--ab. - -It now becomes evident what offspring may result from the union of -parents who have any of the above constitutions. Thus parents both of -Group I may have offspring belonging to any group according to which -of the five possible constitutions they possess. If the union be -represented by - - AB--AB × AB--AB, - -then only offspring of Group I can result, since every gamete -contains both A and B. The other possibilities may be worked out by -the reader if he desire. - -Similarly, a union of Groups I × II, I × III, or II × III may produce -any of the groups, definite limitations being imposed by the detailed -constitution of the parents. On the other hand, the remaining group -unions that are possible can only produce a more limited variety of -offspring. Thus II × II or II × IV can only produce Groups II or IV; -III × III or III × IV can only produce Groups III or IV; IV × IV can -only produce Group IV. - -The Mendelian theory of inheritance in general has been subjected to -a prolonged and widely ramifying series of tests, and it seems in the -present state of knowledge to present a satisfactory and consistent -explanation of the facts. For a more extended account of it the -reader must be referred to the standard works on the subject.[6] -As regards its application to the present case, the test of actual -experiment has not yet been carried out on a large scale. A series -of observations has, however, been published by J. R. Learmonth, -who, taking forty families at random, determined the blood groups of -both parents and the children in each family. In this way he tested -most of the possible group matings, and, with a single exception, -the group inheritance conformed to the theory as set out above. -Additional confirmation of the truth of the theory is afforded by -the pedigree given on the page opposite. I have recently collected -this pedigree, which includes fifty-nine individuals belonging to -four generations, and it has not been published before. It will -give, perhaps, a more graphic representation of the facts than has -been conveyed by the brief summary contained in the foregoing pages. -It does not show any variation from the results that were to be -anticipated according to the theory. - -The exceptional result obtained by Learmonth in one of his forty -families serves to emphasize the clarity of the theoretical -considerations. In this family parents both belonging to Group IV had -a child showing the reactions of Group I. There are three possible -explanations of this: - -(1) The observations were at fault. - -(2) The putative father was not the real father. - -(3) The Mendelian theory of inheritance is wrong. - -The Mendelian theory is established on so firm a basis that, in the -absence of more numerous exceptions, (3) may be rejected. There is no -reason for supposing that the observations were inaccurate, and we -are therefore brought to the conclusion that in such a case the child -is illegitimate. - -[Illustration: Fig. 6.--PEDIGREE SHOWING INHERITANCE OF BLOOD GROUPS -THROUGH FOUR GENERATIONS. THE GROUP OF EACH INDIVIDUAL IS INDICATED -BY A NUMERAL. THOSE WHO WERE NOT AVAILABLE ARE REPRESENTED BY A O] - -The conclusions which emerge from this structure of theory and fact -are obviously of very great clinical importance. It is now clearly -demonstrated that a mother belonging, say, to Group I, may give -birth to a child belonging to any one of Groups I, II, III, or IV; -her blood may not be used for transfusing her child without a grave -risk that the “maternal threat” may culminate in the death of the -child. The same applies to the possible relations between a father -and his child. Two brothers, again, may belong to Groups II and III -respectively. Even the blood of twins may be mutually incompatible, -except in the rare case of “identical twins,” who, it may be supposed -on theoretical grounds, would certainly belong to the same group, -though I am not aware of a case in which this has been put to the -test. As much care, therefore, must be exercised in testing the blood -groups of members of the same family before performing a transfusion -as would be taken before using a donor who is not related to the -patient. - -The medico-legal importance of the facts concerning the inheritance -of blood groups is also evident, and, although this test has not yet -been used as a test of legitimacy, there can be little doubt but that -it will be so used in the near future. The information to be derived -from it is of a negative rather than a positive character. Thus the -occurrence of Group III blood in a child whose mother is of Group II -and putative father of Group I cannot be taken as a proof either of -legitimacy or the reverse. But if, as in Learmonth’s case, parents -both of Group IV have a child of Group I, or if parents both of Group -II have a child of Group I or III, then this may be taken as a proof -of illegitimacy. - -There is not much experimental evidence concerning the effect of -various pathological conditions on the agglutination reactions of -the blood and serum. It has already been mentioned that there is no -proof that the possession of any particular blood group confers -upon its owner any special immunity from, or liability to, disease. -The numbers, investigated by Alexander in the communication referred -to on p. 81, are too small for the observation to be of much value; -it is also necessary, as a preliminary to any such research, to -demonstrate that there is no abnormal alteration in the reactions of -the blood of these patients. It is probable, indeed, that evidence of -this alteration in malignant disease already exists, for a reference -to it is to be found in Kolmer’s work on serum-therapy,[7] but I have -been unable to find a record of the investigation. - -I possess, on the other hand, evidence that an alteration may take -place in some other diseases, such as pernicious anæmia and familial, -or acholuric, jaundice. Evidence for the former was provided -recently by a patient whose condition was typical, clinically, of -the last stages of the disease. Her corpuscles, tested with stock -sera, belonged to Group II, but her serum, tested directly with -the corpuscles of prospective donors known to belong to Group IV, -agglutinated these vigorously, so that a transfusion could not -safely be performed. The same phenomenon has been found by other -observers. In acholuric jaundice there is a progressive destruction -of red corpuscles in the patient’s circulation. This appears to be -connected in some way with an abnormal functioning of the greatly -enlarged spleen, since the destruction of corpuscles ceases almost at -once when this organ is removed. There seems to be, in addition, an -alteration in the blood reactions. In a case which I tested recently, -the patient’s corpuscles were quickly agglutinated by serum of Group -III, and he therefore nominally belonged to Group II. His serum, -however, when separated and tested against other bloods of known -groups gave, in addition to a rapid agglutination of corpuscles -belonging to Group III, a definite, though slower, agglutination -of corpuscles belonging to Groups II and IV, showing that it had -acquired abnormal properties. - -It is possible that there are similar alterations of reactions in -other pathological conditions. The instances mentioned above suggest -that the serum is affected rather than the corpuscles, but further -investigations are needed. It is an observed fact that blood outside -the body soon develops the property of auto-hæmolysis. If blood -is drawn from a vein, put into a test-tube, and allowed to clot, -then after twenty-four hours or more the serum which has separated -from the clot begins to be tinged with hæmoglobin, even though it -has remained absolutely sterile. It appears, therefore, that the -serum develops a hæmolysin and the corpuscles the corresponding -iso-hæmolysin, the interaction of which results in the breaking up -of corpuscles. If this process takes place in normal blood outside -the body, it would not be surprising to find that it may also occur -abnormally inside the body. This actually happens in the condition -known as paroxysmal hæmoglobinuria. The pathology of the disease is -obscure, but it seems that a hæmolysin develops in the serum as the -result of cooling in the extremities and hæmolysis takes place when -the cooled serum is again warmed by being restored to the general -circulation. The presence of this hæmolysin in addition to the normal -hæmolysins has been demonstrated by Moss. It is possible that a -similar though less acute change takes place in acholuric jaundice. -Blood transfusion, therefore, is not likely to be efficacious in such -conditions, since the transfused corpuscles may be destroyed whatever -the apparent blood group of the patient. Some of the facts of -auto-hæmolysis have been recently investigated by Bond, but it is not -necessary to give the details here. He concludes that the development -of auto-hæmolysins, which are non-specific and independent of -the specific hæmolysins of the blood groups, has a biological -significance in the history of the red corpuscle, and is a product of -ageing. The biochemistry, however, of the process remains at present -entirely unknown. - -The necessity for careful blood grouping in every case before -performing a transfusion has now been sufficiently emphasized, but -before proceeding to the description of the methods of choosing a -donor and of grouping, a possible danger must be mentioned which may -arise even when the blood groups are known. In the preceding chapters -references were made to the effects which have been observed to -follow repeated transfusions given in the treatment of a condition -such as pernicious anæmia. In such cases, although the groups were -ascertained, and the bloods were also tested directly against one -another without any incompatibility being detected, yet when the -third or fourth transfusion was given, symptoms of toxæmia followed, -sometimes with hæmolysis. The death of the patient has even been -hastened in this way. A very striking instance of this phenomenon, -which has been recently reported (278), will serve to bring home the -reality of the danger. A boy was transfused by the citrate method -with blood from his father, and this was followed only by a mild -febrile reaction such as is often observed. Eighteen days later a -second transfusion with blood from the same donor was performed, and -after 150 cc. had been given, a severe reaction resulted, which was -followed later by pronounced hæmoglobinuria. In this case the bloods -of donor and recipient had been tested against one another directly, -but this was not repeated, and the groups were not ascertained until -afterwards. Probably there was some error in the original test, for -it afterwards appeared that the boy belonged to Group I and his -father to Group III, so that there should have been agglutination -of the boy’s corpuscles by his father’s serum outside the body. -Nevertheless, Group I individuals have been called the “universal -recipients,” and no ill effects are usually observed whatever blood -be used for transfusing them. In the other cases already mentioned -a reaction followed the later transfusions, even when the donor and -recipient belonged to the same group. It appears that by repeated -transfusions the recipient becomes as it were sensitized to the -blood of another individual even of the same group, and consequently -great caution must be used in giving the later transfusions of a -series. Some light is thrown on this question by the observations of -Ottenberg, already referred to, concerning the artificial production -of iso-hæmolysins in cats. In these animals iso-agglutinins are -found, but iso-hæmolysins seldom or never. The reaction is, however, -found to become hæmolytic in the recipients of transfusions, and it -is then selective. It seems, therefore, that the group reactions -may not be as clearly defined as was at one time supposed. Probably -there are slight incompatibilities of an unknown nature between -individuals of the same or compatible groups. These are very seldom -of any consequence in a first transfusion, but become accentuated -as the result of “sensitization,” and in later transfusions have -a pronounced influence. This “over-lapping” of groups has been -mentioned on another page. It must not be supposed that any untoward -results follow repeated transfusions as a general rule, for usually -no such effect is observed. In order, however, to minimize the risk, -it may be suggested that the following precautions should be taken: -(1) The donor should be actually of the same group as the recipient, -and not merely of a theoretically compatible group; a patient, for -instance, of Group II should receive blood of Group II rather than -of Group IV. (2) The same donor should not be used for the later -transfusions of a series, on the grounds that the sensitization -appears to be an individual rather than a group phenomenon. (3) In -performing the later transfusions, the blood should be given at first -very slowly, so that it may be discontinued at the first appearance -of any signs of a reaction. - - - - -CHAPTER VI - -THE CHOICE OF BLOOD DONOR - - -The physiology of blood groups having been examined, the principles -governing the choice of a blood donor can be more readily understood. -It is evident that this choice is determined largely by blood groups, -and in the present chapter therefore the clinical methods of testing -for the groups will be described. - -Before, however, the bloods can be tested, a willing donor must -be found, and this is not always an easy matter. During the war, -even when transfusion was being practised on a large scale, there -was never any difficulty in finding volunteers among the men that -were more lightly wounded. In addition to the genuine and ready -response which many men would make at once to a call for help in a -matter of life and death, there was the glamour of novelty and the -feeling of satisfaction following an act of conscious heroism--for -such the sacrifice of blood was held to be, the days having long -been forgotten when as much blood was “let” in the treatment of -almost any ailment. In the Expeditionary Force, too, the unofficial -reward of a fortnight’s leave in England proved a potent inducement, -and the rejection of a volunteer on the ground of incompatibility -was regarded almost as an injustice or as a reflection upon the -physical condition of the candidate. In civilian life, however, such -inducements cannot be held out, and it will be found that many a -man “does not like the idea” of parting with a pint of blood, even -though the sacrifice may save another’s life. Often, however, a -near relative of the patient may happen to be willing and suitable, -or, failing this, in a hospital ward there will usually be some -young man who has been admitted for a slight operation, such as the -radical cure of a hernia, and will accede to a request for blood -if the procedure, its object, and its harmlessness to himself be -briefly explained. Notoriety is fortunately seldom a motive for -volunteering, and though paragraphs have occasionally appeared in the -daily press with headings such as “Police Inspector’s Sacrifice,” -this has probably not been done by the donor’s own wish. It is, after -all, natural that to the mind of a layman the giving to another of -so personal a possession as his blood should seem to be an act of -heroism, and it is also natural that occasionally a man should feel -some repugnance to taking part in a strange performance which he but -dimly understands. To the young, on the other hand, the procedure may -appeal by its faint flavour of adventure. - -Occasionally during the last two years advertisements for blood -donors have appeared in newspapers, probably not in vain. If the -demand for blood donors becomes greater than it has been as yet, it -will certainly result in the creation of a class of “professional -blood donors,” who already exist in some numbers in the United States -of America, where blood transfusion is a more widely recognized form -of therapeutics than it is in this country. These professionals have -even formed a Trade Union, so that as high a fee as possible may be -obtained from those who need their blood. Apart from this, some of -the advantages of having these professionals available have already -been explained in the chapter on the dangers of blood transfusion. -It is evident that certain sources of danger can be eliminated in -advance, and in an emergency it is obviously better to have donors -of known groups available, so that no time is lost in testing the -prospective donors of whom several in succession may be found -unsuitable. Probably it will be easier for practitioners to arrange -for such professionals to be available at the shortest notice than -for necessary arrangements to be made in a hospital. Even in large -institutions it is usually difficult for any of the men employed in -them to be spared from their work for twenty-four hours, so that, -although suitable men of known groups are always within call, it may -be impossible to use them. This, however, is not the place to discuss -the organization that is necessary to make a blood transfusion a -really efficient form of emergency treatment in a hospital. It may -merely be observed that in every hospital it should be possible -to give a blood transfusion to a patient suffering from urgent -hæmorrhage within fifteen minutes of his arrival on the premises. - -Whether the donor be a “professional” or an “amateur,” it may be -useful to mention a few points to be observed in choosing him. There -can be no doubt that the most satisfactory individuals for the -purpose are young men between the ages of eighteen and twenty-five. -The younger the donor, the less likely is he to be suffering from -certain of the diseases mentioned in the chapter on the dangers, the -less will be the immediate effect of the withdrawal of circulating -fluid, and the more quickly will he recuperate from the loss of blood. - -It must not be supposed, however, that the withdrawal of even 1,000 -cc. of blood will usually have an appreciable effect upon a healthy -man. It is impossible to predict from the donor’s appearance what -immediate effect the loss of blood will have upon him. It sometimes -happens that the most robust-looking individual becomes faint after -losing a few hundred cubic centimetres, whereas another, to all -appearances pallid and much less satisfactory, will not evince the -slightest discomfort from the loss of 750 cc. or even more. Normally -a man should be able, by his physiological mechanisms, to compensate -reflexly and at once for the removal of this amount of fluid from -his circulation. In any case, the worst effect that is seen in a -well-chosen donor is a transient faintness; it is usually wise to -keep him on his back for two or three hours after the operation, and -he should not, if it can be avoided, return to his work on the same -day. During the late war a medical officer of my own acquaintance -gave 750 cc. of blood for a severely wounded friend and continued -his arduous duties as Surgical Specialist in a Casualty Clearing -Station immediately afterwards. In this case, however, the donor was -solely responsible for his own welfare; usually this responsibility -rests upon another, and greater care must be exercised. The effect, -indeed, of a transfusion upon the donor seems to depend more upon -psychological than upon physiological factors. A nervous and -excitable donor is more likely to suffer than one who approaches the -operation without apprehension. This is another point in favour of -employing a professional donor, who soon becomes familiar with the -whole procedure and will lose all symptoms of fear. - -The same considerations may be applied to the use of women as blood -donors. In them the spirit of self-sacrifice is commonly more highly -developed than it is in men, and some of the most eager donors will -be found among them. The disability of nervousness will, however, -occur more often in women, and another consideration of importance -is that the veins of a woman are usually much less easily accessible -than those of a man. Not only is the abundant subcutaneous fat an -impediment in women, but usually the superficial veins are all of -small size. The method of choice for performing a blood transfusion -will be presently described, and it will then be seen that the -operation is easier and that much less damage is inflicted on the -donor if a large superficial vein can be tapped. In women this will -very often be difficult or even impossible. In general, therefore, it -may be stated that the use of women as blood donors is to be avoided. -The fallacies concerning the indiscriminate transfusion of an infant -with its mother’s blood and of any patient with the blood of a near -relation have already been explained. - - -TESTING FOR BLOOD GROUPS - -Reference to the table of blood reactions given on p. 71 will show -that in order to discover the blood group of any individual it is -only necessary to test his corpuscles against the serum of Groups II -and III. These reactions may be recapitulated as follows: - - (i) If he be Group I, his corpuscles will be agglutinated by the - serum of Groups II and III. - - (ii) If he be Group II, his corpuscles will be agglutinated by the - serum of Group III only. - - (iii) If he be Group III, his corpuscles will be agglutinated by - the serum of Group II only. - - (iv) If he be Group IV, his corpuscles will be agglutinated by - neither serum. - -Only the serum, therefore, collected from people known to belong -to Groups II and III need be kept in stock. This can generally -be obtained from the Lister Institute, and if kept sterile will -retain its agglutinating properties for some months, but under no -circumstances should serum more than six months old be used, since -the consequences of a failure to agglutinate may be very serious. -Nevertheless, the agglutinins contained in serum are very resistant -to physical and chemical changes in their environment. Dried serum -has been successfully used for testing purposes, and Culpepper has -shown that the reactions are not interfered with by cold or by -heat until actual coagulation of the serum takes place. Bacterial -contamination does not affect the reactions, so that the serum is -still active even when putrid. Various methods have been used for -preserving the serum. Its properties are not affected by the addition -of dilute cresol (1 : 250) or of chloroform. - -In the absence of any stock sera, the agglutinating test may be -applied directly. A few cubic centimetres of blood are taken from -the patient, and the serum as soon as it has separated is tested -against the corpuscles of the prospective donor. If agglutination -occurs, this donor is at once excluded. If no agglutination occurs, -he is either of the same group as the patient or belongs to a -compatible group. Supposing that a donor actually of the same group -as the patient is wanted, then the reverse test must be performed -in addition, that is to say, the corpuscles of the patient must be -tested against the serum of the donor. If both tests are negative, -then donor and patient are proved to be of the same group. The method -of direct test cannot be applied in an emergency owing to the loss of -time involved; it is better, therefore, that anyone who intends to -be ready to perform a blood transfusion should always have serum of -Groups II and III immediately available. - -The collection of stock sera is not a matter of any difficulty. With -strict aseptic precautions 20 cc. of blood are withdrawn in a syringe -from persons known to belong to Groups II and III; the bloods are put -into a sterile test-tube and allowed to clot. As soon as the serum -has separated it is drawn up into sterile glass bulbs of suitable -capacity, which are sealed off at each end. The most convenient -form of storage for actual use is a capillary glass tube sealed at -each end. Each tube may be made to hold a single drop, which is the -amount used for a test. There is then no wastage of serum, and no -chance of contaminating the remaining stock. When the blood has been -withdrawn and has clotted, the complete settling of the corpuscles -can be hastened by the use of the centrifuge. If the serum be left -in contact with the corpuscles for more than twelve hours, some -auto-hæmolysis may take place, so that the serum will become tinged -with hæmoglobin. It is exceedingly important that the two stock sera -should not become confused, and this may easily happen unless each -tube has some distinguishing mark. - -The methods of testing for blood groups have been simplified by -successive observers since the existence of the groups was first -demonstrated in 1907. Moss used an elaborate technique such as was -essential for putting a new discovery upon a secure scientific basis. -In order to obtain a suspension of corpuscles, blood was drawn into a -syringe containing a solution of sodium citrate to prevent clotting. -The corpuscles were collected by means of the centrifuge, and were -thoroughly washed twice in normal saline solution so that they -were finally collected free from serum and from citrate. Serum was -collected in the manner already described. A series of small tubes -was then filled with equal quantities of serum and the suspension of -corpuscles, and was incubated for two hours at 37·5° C. At the end of -this time observations were made and again after the tubes had stood -for twelve hours in an ice chest. Varying degrees of agglutination -and hæmolysis were then accurately recorded, and far-reaching results -were obtained. - -Later workers had the advantage of using stock sera belonging to -known groups, so that the number of observations to be made was very -greatly reduced. Brem introduced in 1916 a method of testing in -which he mixed the serum and suspension of washed corpuscles in very -small quantities on a coverslip, which was inverted over an ordinary -cell slide rimmed with petroleum jelly. The results could then be -observed macroscopically or under the microscope, and the presence or -absence of agglutination could be determined within fifteen minutes. -The detection of hæmolysis by the hanging drop method requires that -the cells should be incubated and observed at intervals for several -hours, but it is not always easy to see the disintegrated corpuscles -unless the process has taken place extensively. The diagram on p. 105 -gives in a tabulated form some idea of the appearances presented by -the corpuscles of the different groups when mixed with the stock sera -and observed in a hanging drop under a microscope. Agglutination must -be distinguished from the formation of rouleaux, which may be seen in -any of the mixtures. - -For scientific purposes these very careful tests are necessary, -but it seems to be clear that for clinical purposes a much rougher -and quicker test is adequate. In the clinical determination of -blood groups it is superfluous to carry the test to the point of -watching for hæmolysis, for it is upon the presence of agglutinins -in the serum and the corresponding iso-agglutinins in the corpuscles -that the determination of the groups depends. Further, no error is -introduced by neglecting the hæmolysis, since it has been shown -that hæmolysis is invariably preceded by agglutination. It is the -occurrence of agglutination therefore that is of prime clinical -importance. If that is excluded, hæmolysis is necessarily excluded -also, and the prolonging of the test is seen to be only of academic -interest. In the methods described above the corpuscles were always -tested in the form of a washed suspension. This precaution was taken -on the supposition that the presence of any of the serum belonging to -the corpuscles might interfere with the reaction. If, however, the -amount of this serum be small relatively to the amount of the test -serum, then no such interference takes place. - -[Illustration: Fig. 7.--TABULATION OF SERUM REACTIONS AS SEEN IN -HANGING DROPS.] - -The ordinary clinical method of testing may therefore be greatly -simplified, and the one commonly used at the present time is as -follows: A single drop of each of the stock sera is placed on two -glass slides, or, better, side by side upon a white glazed tile or -plate, the numbers of the groups, II and III, being written above the -respective drops. The lobe of the ear of the person to be tested is -then washed with ether and pricked with a sterile surgical needle. A -small quantity of the blood which exudes is taken up on the end of -a blunt metal or glass rod, and is intimately mixed with the drop -of serum under the number II. The end of the rod is then carefully -wiped clean, and a similar small quantity of blood is mixed with -the drop of serum marked III. The amount of blood to be used should -not be so great as to make the drop of too deep a colour, which -may interfere with observation of the reaction, but it should be -enough to impart to it a very definite red tint. The slide or tile -is then gently rocked, so that some slight movement is imparted to -the drops, which are at the same time closely watched in a good -light. The agglutinating reaction is readily seen with the naked -eye, especially against the white background provided by the tile. -If the serum be properly active, the agglutination of the corpuscles -begins to be apparent as a definite granular appearance resembling -brick dust within a minute of mixing. With a little practice this -appearance is easily recognized, but it must be distinguished from -the appearance produced by a mechanical gravitation of the corpuscles -towards the centre of the drop. If agglutination is taking place, the -granulation appears simultaneously throughout the drop, and not only -in the centre. With an active serum the process may proceed rapidly, -so that in less than five minutes the corpuscles have been aggregated -into a few irregular masses; often it stops short of this, but the -drop presents, nevertheless, a coarsely granular appearance which is -quite unmistakable. If no granulation can be seen at the end of five -minutes, it can be assumed that the test is negative for the serum of -that group, and the group of the corpuscles may be deduced upon the -principles already explained. - -The test carried out in this way is admittedly not susceptible of -the same finesse as if it were done with the assistance of the -hanging drop, the incubator, and the microscope; nevertheless, my own -experience in a large number of cases has shown that, clinically, -this test may be relied upon, and the same view has been expressed -by other writers on the subject. Very seldom is there any doubt as -to the presence or absence of agglutination. When doubt exists, it -is easy to repeat the test and obtain a confirmation of the result. -It may perhaps be urged that this test is quite insufficient for -eliminating the slighter degrees of incompatibility which have -produced serious results when the transfusion has been repeated -several times. But in the cases reported, the blood that was used -had not shown any agglutination even when most carefully observed -under the microscope. It seems, therefore, that the results were -probably due to another factor, as already suggested (see p. 57), -which the more elaborate test failed to eliminate. The efficiency of -the rapid test is therefore not invalidated. It is, nevertheless, -in the present state of knowledge, a wise precaution to perform -the direct test between patient and donor in addition to the group -test when circumstances permit. It is essential when the patient is -suffering from any form of blood disease. It is unnecessary when -the transfusion is to be performed as a life-saving operation in -hæmorrhage or shock. - - - - -CHAPTER VII - -THE METHODS OF BLOOD TRANSFUSION - - -Some reference has already been made in the first chapter to the -rapid development in recent years of the technique of performing a -blood transfusion. The earlier operators, owing to the difficulties -introduced by the coagulation of blood outside the body, were -constrained to make use of some method of direct transfusion, the -blood flowing directly from an artery of the donor into the patient’s -veins. This has now been largely replaced by one of the methods of -indirect transfusion, the blood being withdrawn from the donor into a -vessel in which clotting is delayed or prevented, and then injected -or allowed to run into the patient’s circulation. - - -=Direct Transfusion.=--The obvious method of performing a direct -transfusion is by making an end-to-end anastomosis between an artery -of the donor and a vein of the recipient. The most readily accessible -artery is the radial at the wrist, and this is indeed almost the -only artery that is available. The most accessible vein is the -median basilic or the median cephalic at the elbow. The operation -of end-to-end anastomosis, using an artery of so small a calibre as -the radial artery at the wrist is usually found to be, is one of -great technical difficulty; this effectually prevented transfusion -from being used at all frequently. A modification has been used by -Sauerbruch and others, in which the end of the radial artery is drawn -into the lumen of the vein through a slit in its wall. A suture is -passed through the radial artery close to its cut end, and the needle -is then passed through the slit in the vein and out again through -the wall of the vein an inch or so higher up. Traction on the suture -then pulls the artery into the vein. The artery has meanwhile been -temporarily occluded by a clip, which is removed when the artery is -inside the vein, so that the blood can then flow from one to the -other. This is easier to do than the anastomosis, but, in addition to -the other objections to direct transfusion to be mentioned presently, -the difficulty occurs of occlusion of the artery by the physiological -process of inversion of its coats at the cut end. This is likely to -happen before much blood has passed, so that apparent success at -first is often not maintained. Sauerbruch claimed that the amount of -blood that had passed could be estimated by measuring the time taken -for 1 cc. of blood to flow from the artery before it was introduced -into the vein; but there is no proof that the rate of flow remains -constant. - -If direct transfusion be desired, there can be no doubt that Crile’s -method, introduced some fifteen years ago, is the best to employ. -After much patient work Crile perfected a method of anastomosis -which ensures that no occlusion of the vessels can take place at the -site of junction. This depends on the use of a short silver tube, -through which the end of the artery is threaded. The artery is then -pulled back again outside the tube in the form of a cuff and fixed -in position. The end of the artery has thus been made rigid, and -over this the vein is pulled in its turn and fixed by a ligature. -A watertight junction is thus made, and blood can flow through it -without interruption--unless clotting takes place in the vessels as -the result of handling and injury to their walls. This method has -been extensively used in America, and it was the first to render the -operation of transfusion a comparatively popular one. - -Various other devices for achieving the same result have been -elaborated by other workers, and attention may be drawn to those of -Elsberg and Bernheim, both of which are described in the book by -the latter on “Blood Transfusion.” During the war a simpler method -was introduced by Colonel Andrew Fullerton, who, working at a -Base Hospital in France, found that he could get good results by -employing a thin rubber tube with a small silver cannula at either -end. The apparatus was first coated on the inside with a thin layer -of paraffin wax, in order to discourage clotting within the tube, -and the cannulæ were introduced into the donor’s artery and the -recipient’s vein respectively. The blood could then flow freely -from one to the other. The fact that blood was being transmitted -was taken to be proved by the visible pulsation of the thin rubber -connecting-tube synchronously with the arterial pulsations. The -disappearance of this was assumed to be evidence that clotting had -occurred. This method was described by Colonel Fullerton to the -surgeons working at the Casualty Clearing Stations, where blood -transfusion was likely to be of most service, but it was never used -extensively. The coating of the inside of the tube with paraffin is -in itself an operation of some difficulty. Under conditions in which -any loss of time could not be permitted, success by this method was -not attained with sufficient certainty, and it was shortly afterwards -replaced by the more satisfactory methods described below. The most -recent work on direct transfusion has been done by J. M. Graham at -Edinburgh, who has however reached the conclusion that the technique -is always more difficult than that of indirect transfusion. - -It can easily be seen, therefore, that all the known methods of -direct blood transfusion present great technical difficulty, which -renders the method unsuitable for general use. There are, in -addition, certain other objections to it of an obvious nature. It is, -in the first place, impossible to measure the amount of blood which -has passed from the donor to the recipient. Sometimes an indication -may be obtained from the evident improvement in the condition of the -patient, accompanied by the signs of loss of blood in the donor. -More often clotting takes place, unknown to the operator, at some -point, with the result that blood ceases to pass a considerable time -before the end of the operation, and the patient has consequently -received very much less blood than is supposed. It has been claimed -by Libman and Ottenberg that the amount of blood transferred may -be estimated by weighing the donor before and after the operation. -This presupposes that a very accurate weighing machine is easily -available, which usually is not the case. - -A second objection is the extent of the injury which is necessarily -inflicted on the donor. His radial artery must be exposed through -an incision of considerable length, and must be ligatured at the -conclusion of the process. The operation becomes, therefore, a matter -of some moment to the donor, who will be permanently scarred, and can -under no circumstances be used for transfusion more than twice. - -A third objection is that the transfusion cannot be done with due -regard to the condition of the patient. A delicate and difficult -operation has to be performed with the donor and recipient lying side -by side, their arms close together. It is therefore almost imperative -that both should be on operating-tables of a convenient height. -Often, however, with an exsanguinated patient it is very important -that he should not be moved from his bed, but as a bedside operation -direct transfusion becomes difficult indeed! - -A final objection is that in some people the radial artery is of very -small calibre, so that when all preparations have been made, and -the artery exposed, it is found to be quite impossible to proceed. -Another element of uncertainty is thus introduced. - -There is, therefore, little to be said in favour of direct -transfusion, and much to be urged against it. This method has, -indeed, in my own opinion, come to be of historical interest only. -For this reason the different methods have only been very briefly -described. For more detailed information, reference must be made -to the various original communications, which will be found in the -Bibliography. - - -=Indirect Transfusion.=--The methods of indirect transfusion may -be divided into those which depend upon the use of an anticoagulant -mixed with the blood and those in which the blood is given -unaltered. The technique of either process is simple compared -with that of direct transfusion, though any method which makes -use of whole blood can never be quite as free from uncertainty or -difficulty as one which introduces the use of an anticoagulant. If -the blood is prevented from clotting, the chief cause of failure -in performing blood transfusions is removed. With any whole-blood -method of transfusion speed is exceedingly important, frequent -practice is a very great advantage, and it is essential, as with -direct transfusion, that the donor and recipient should be in close -proximity to one another, if not actually side by side. - -On the other hand, the use of an anticoagulant renders speed and -frequent practice of less account. The blood can be drawn, and can -then be put on one side until the best moment for giving it has -arrived. Due regard may be had to the patient’s condition, since the -blood can be carried about and can be given at leisure to the patient -in his bed without disturbing him and almost without his knowing it. -The donor, too, is not exposed to the mental shock of lying for some -time side by side with a patient who may be _in extremis_, or may -even expire during the operation. - -There are, however, those who consider that the use of whole blood, -instead of blood which has been chemically treated, has advantages -which outweigh the possible disadvantages mentioned above. Two -methods of using whole blood are, therefore, described first; the use -of anticoagulants is then described in detail, and their advantages -and possible dangers are enlarged upon. - - -=Whole Blood Transfusion with Syringes.=--It is obvious that, if -blood can be drawn from the donor’s vein into a glass syringe and -injected into the recipient so rapidly that clotting has no time to -occur, then a transfusion of any quantity of blood that may be wished -can be given by this simple means. The measure of the amount of -blood transfused is given by the number of syringes that have been -filled and emptied. This method has been successfully used by several -workers, and it has the advantage that no very special apparatus is -necessary. It does, however, require that several syringes, and more -than one assistant, should be available, since clotting will take -place in the syringes, unless they be frequently washed out. There is -also the possibility that clotting may take place in the needle which -is introduced into the donor’s vein, since this cannot be withdrawn -and replaced for each syringeful of blood that is transferred. With -practice, however, and with good assistants, the process can be done -quickly enough to avoid this. Wide-bore needles with short rubber -connexions are introduced into the veins of donor and recipient; -if, as often happens, this is difficult to do through the skin in -the case of the recipient, his vein must first be exposed through -an incision and a glass or metal cannula introduced into it. The -operator then fills the syringes with blood in quick succession and -hands them to his first assistant, who injects the blood into the -recipient. Blood is prevented from escaping from the needles when -the syringes are disconnected by nipping the rubber connexions with -the fingers. The first assistant passes the empty syringes to the -second assistant, who washes them out with normal saline, and hands -them back if needed to the operator. This can be done with six 20 cc. -syringes used in rotation, possibly with only four. - -The most recent description of this method has been published by -J. M. Graham of Edinburgh, who has introduced an improved form of -needle. This consists of a double tube; the inner tube has a needle -point which is used for puncturing the vein, and can be withdrawn -into the blunt outer tube when the vein has been entered. Any further -wounding of the vein is thus avoided. In addition, movement of the -needle-cannula is prevented by a bull-dog forceps attachment, which -is clipped to the skin. Graham finds it advisable to lubricate the -cannulæ and syringes with vaseline before being used. He also -states that: “As the absence of clotting depends upon the rapidity -with which the syringes are filled and emptied, a series of syringes -should be used in strict rotation, and all trace of blood must be -washed out with saline before the syringes are used again. One -or two additional assistants are necessary for this method.” The -disadvantages are evident, and it is not suitable for general use. - -A modification of the method has been described by Unger, in which -only one syringe is used. The barrel of this is cooled by an ether -spray so that clotting is discouraged or prevented. - - -=Whole Blood Transfusion with Kimpton’s Tube.=--The principle of this -method depends upon the use of paraffin wax as a coating for the -vessel into which the blood is drawn, so that clotting is prevented -or greatly delayed. The form of the vessel has been modified by -different workers, but the essentials are the same in each. One form -of the apparatus, known as the Kimpton-Brown tube, is illustrated in -the accompanying diagram. It consists of a graduated glass cylinder, -of about 700 cc. capacity, the lower end of which is drawn out into -a cannula point at an acute angle with the body of the cylinder; the -point is of a size convenient for introducing into a vein and its -bore large enough to allow of a free flow of blood through it. Near -the upper end is a side tube to which a rubber tube can be attached, -and an opening at the top is closed by a rubber bung. An ordinary -rubber double-bulb bellows is the only other apparatus that is needed. - -[Illustration: Fig. 8.--KIMPTON-BROWN TUBE] - -The glass vessel is first sterilized in the autoclave, and then it -must be coated on the inside with a thin layer of paraffin wax. -The whole success of this method depends upon this wax coating -being absolutely complete right up to the tip of the cannula at -the bottom. If the tiniest area of glass be left exposed in the -cannula, the process will fail. The production of this perfect wax -coating used to be exceedingly difficult of attainment without very -frequent practice. The apparatus was first raised to exactly the -right temperature; sterile, melted paraffin was then put into it, -and distributed evenly over the surface, excess being allowed to -run out. The apparatus was then cooled down, and could be put away -in a sterile towel ready for use, great care being taken that the -lumen of the cannula was patent and not blocked with excess of -wax. A simplification of the process was introduced by the use of -a saturated solution of wax in ether. This solution is put into -the vessel, which must not be heated, and is made to run all over -the surface, excess as before being allowed to escape through the -lower opening. The ether quickly evaporates, leaving a very thin and -perfect film of wax over the surface of the glass. As before, it must -be ascertained that the lumen of the cannula is patent. The apparatus -is then ready for use. - -The donor and recipient need not be lying close together, but they -must be in the same room. A vein is exposed in the arm of each by -dissection under a local anæsthetic. The operator then picks up the -vein with a pair of dissecting forceps, and makes an oblique cut into -the lumen as in the diagram on p. 131. A flap is thus made which is -held in the dissecting forceps in the left hand or is picked up with -a fine-pointed pair of artery forceps. The Kimpton’s tube is taken -in the right hand, and the point of the cannula is introduced into -the vein; that part of the lumen lying opposite the flap serves as a -gutter which guides the cannula directly into the lumen, so that it -is introduced without any fumbling or delay. The cannula is pushed -on so that its widest part engages the whole circumference of the -vein, forming a joint through which blood does not leak. The cannula -having been pushed well up into the vein, the forceps holding the -venous flap may be let go. At the same time an assistant grips the -donor’s upper arm, or some form of tourniquet of the necessary degree -of tightness is applied, so that the veins become congested without -obliteration of the arterial pulse. Blood now flows rapidly into -the tube, and the venous pressure is always sufficient to overcome -the counter-pressure of the increasing head of fluid in the tube. It -is unnecessary, therefore, to produce any negative pressure within -the tube with a reversed Higginson’s syringe or an exhaustion pump, -which has been used by some workers. Blood is allowed to flow into -the tube until the requisite amount has been obtained. The venous -congestion is then released, and at the same time the tube and -cannula, held at the lower end with the right hand in such manner -that the index finger is free, is withdrawn from the vein. At the -moment of withdrawal the end of the cannula is closed with the right -index finger. To prevent hæmorrhage from the donor’s vein, a ligature -previously put round it is tied by an assistant, or pressure on it -is maintained with a sterile swab. The operator must now, without -a moment’s delay, carry the tube filled with blood over to the -recipient. An opening in his vein is made by an assistant in the same -manner as already described, the finger is removed from the cannula, -and its point is instantly introduced into the vein. It is now -necessary to produce some degree of positive pressure in the tube to -ensure that the blood shall at once begin to flow steadily into the -vein. This is done with a rubber bellows, attached by an assistant to -the upper side tube, and the level of the blood in the tube should -at once begin to fall. Great care must be taken that the positive -pressure is released before the tube is completely emptied of blood -in order to avoid the obvious danger of the entry of air into the -patient’s vein. When the tube is nearly empty it is withdrawn, the -vein is ligatured, and the wounds in donor and recipient are sutured. -The most convenient pattern of Kimpton-Brown tube holds only about -500 cc. of blood, so that if more is needed, the process must be -repeated. - -There is virtually only one cause of failure in transfusion by this -method, and that is the occurrence of clotting in the cannula or -at the bottom of the tube. If it does occur at any stage of the -operation, it cannot be remedied. It may happen when the tube is -nearly full; if so, the blood that has been withdrawn cannot be used. -Clotting may be due to an imperfection in the paraffin coating on -the glass, but if there is any delay from any cause, it may take -place independently of this. The method is therefore never absolutely -certain of success even in the hands of an expert, and for general -use it is certainly unsuitable. It was introduced into the British -Army by some of the American surgeons in 1917, and was used by the -writer under the guidance of Major Alton of the Harvard Medical Unit -during the first battle of Cambrai with good results. Many of the -English surgeons, however, soon abandoned it as a routine method in -favour of anticoagulants. There are other objections to it besides -its uncertainty. A vein must be exposed by dissection in both donor -and recipient, so that avoidable injury is inflicted on the former. -It is not a perfectly clean method, some blood necessarily escaping -at each successive stage in the process, though an expert can reduce -this to a minimum. In the hands of a novice it may occasion a very -bloody scene. The whole operation is one of urgency, and the best -interests of donor and recipient cannot always be considered. - -Modifications have been introduced, such as that of Vincent, who uses -an attachment with a needle instead of the glass cannula point. This -obviates some of the objections, but introduces other difficulties, -such as the necessity for coating the inside of the needle with -paraffin wax. The technique can certainly be acquired, and the method -has rendered excellent service in the past, but it has no obvious -advantages except the uncertain one of avoiding chemical treatment of -the blood. - - -=Transfusion with Anticoagulants.=--It will have become evident from -the descriptions of the transfusion of whole blood already given, how -great a difficulty is introduced into the technique of these methods -by the physiological process of clotting in blood outside the body. -It is clear how much the process of transfusion would be simplified -if the clotting were to be prevented. Something has already been said -in the historical sketch of the various means by which this problem -was attacked, and it need only be stated here that the most suitable -substance for this purpose has been found to be sodium citrate. This -method was introduced by Lewisohn as recently as 1915, and it soon -became the method of choice among most of those who tried it. - -The process of the formation of a blood clot has always been one of -the great problems of physiology, and numerous theories have been -propounded to explain it. The theory accepted at the present time -regards the process as a complicated one depending on the presence -in the blood of a number of different factors. This theoretical -explanation may be represented diagrammatically as follows: - -[Illustration: - - Plasma Tissues and Platelets - | \ \_______________ \ / - | \ \ \ / - | \ \ \ / - | Prothrombin Ca Salts Thrombokinase - | \_________ \ / - | \ \ / - | \ \ / - Fibrinogen Thrombin - \ / - \ ___________/ - \ / - Fibrin -] - -The clot consists of fibrin in which blood corpuscles are entangled. -It is clear that if any one of the reacting agents can be removed -or rendered inert the clotting cannot take place. There is only one -inorganic substance taking part in the reaction, and it is this -factor that is more easily removed than any of the others. Calcium -is precipitated in an insoluble form by various chemical reagents, -but it is obvious that for purposes of transfusion the formation -of an insoluble precipitate is not permissible. It is therefore -necessary to use a substance which will form a soluble compound with -the calcium and which is at the same time harmless when introduced -into the circulation. The only substance which has been found at -present to possess both these properties is citrate of sodium. -This forms with calcium a soluble double salt, in which calcium is -rendered inert. It is usually held that the calcium to be active -must be present in the ionized form, but recent investigations by -Vines into the rôle of calcium tend to modify slightly the accepted -view of its action. He has shown that calcium is present in the -blood in two forms, ionized and combined, and that both take part -in the coagulation reaction. He has, in addition, demonstrated that -a quantity of anticoagulant sufficient to combine with the whole of -the calcium present in a given quantity of blood is not enough to -prevent coagulation. It seems, therefore, that the anticoagulant acts -by combining with a large organic molecule of which calcium is only -one constituent, and not merely by combining with ionized calcium. -The organic complex with which the calcium is associated possibly -corresponds to the thrombokinase of the theory. - -About the time that the use of the citrated blood was introduced -by Lewisohn, some investigations upon animals were carried out by -Salant and Wise in order to determine how sodium citrate was dealt -with and eliminated by the body. These observers found that it very -quickly disappeared from the circulation, nearly 90 per cent. of the -salt having been got rid of within ten minutes of its intravenous -injection. Part of the citrate is destroyed by oxidation, and the -rest, 30 to 40 per cent., is eliminated by the kidneys, the urine -being rendered alkaline. It was also shown that if a very large -dose was given, so large that toxic symptoms resulted, the effect -was rapidly obtained; but that if the toxic dose were not fatal, -no remote effects followed. Its injection never resulted in any -albuminuria. - -Lewisohn showed by experiment on the human subject that up to 5 -grammes of sodium citrate in the form of a 0·2 per cent. solution -could be injected intravenously without any harmful results. It -was also shown that this concentration of the salt was sufficient -to prevent clotting outside the body, and that the microscopic -appearance of the blood cells was not altered by the admixture of -this solution. - -Theoretically, therefore, the amount of citrate that should be used -as an anticoagulant should be 2 grammes for 1,000 cc. of blood, or -100 cc. of 2 per cent. solution for 900 cc. of blood. In practice it -is better to err on the side of safety and to use a slight excess of -citrate. This amount of citrate should be used for the 750 cc. of -blood which constitutes the ordinary maximum amount of blood used in -a transfusion. For smaller quantities of blood the amount of citrate -may be correspondingly reduced. - -The use of citrated blood was introduced to the British Army in -France in 1917 by Oswald Robertson, who recommended the use of a -larger amount of citrate than this. His object in increasing the -amount was to produce a solution which, when diluted with the correct -amount of blood, would be isotonic with it. It was thought that a -hypotonic solution might result in some damage to the red corpuscles -by osmosis, and Robertson therefore recommended the use of 160 cc. -of a 3·8 per cent. solution of citrate, which, when mixed with 750 -cc. of blood, will give a solution of which the osmotic pressure -equals that of 0·9 per cent. saline solution. It may be doubted, -however, whether this consideration is of more than theoretical -importance. There can be little doubt that in practice the effect -of a slightly hypotonic solution, such as is given by the 100 -cc. of 2 per cent. solution of citrate, is negligible as regards -destruction of corpuscles. If, however, it be thought necessary, an -isotonic solution may be produced by the addition of sodium chloride. -Other considerations, as will be seen shortly, weigh in favour of -giving the smaller amount of citrate. The dosage to be recommended, -therefore, on practical and experimental grounds is 2 grammes of -citrate in 100 cc. of water for 900 cc. of blood, or 1 gramme of -citrate in 50 cc. of water for 450 cc. of blood or less. These -proportions need not be observed very accurately. Latitude may be -used in either direction without harming either the transfused blood -or the patient. - -It has been stated above that sodium citrate introduced into -the circulation in small quantities, such as are sufficient for -anticoagulant purposes, is non-toxic to man. In the light, however, -of the extended experience of the last four years, it is seen to -be possible that this statement may not be quite literally true. -Probably there is an individual variation in the tolerance of -different people to sodium citrate. Certainly in some cases a -reaction follows the injection of citrated blood. The symptoms of -this reaction are a slight headache, a rise in temperature to two or -three degrees above normal, sometimes accompanied by a rigor or a -sensation of chill, and an increase in the pulse rate. The effect is, -however, always very transitory, lasting only two or three hours, and -is never, in my own experience, attended by any symptoms which need -give rise to anxiety for the patient’s welfare; nor does it in any -way prejudice the therapeutic results of the transfusion. - -That the reaction is caused by the citrate and not by another -constituent of the transfused blood has been believed by several -observers. In a case seen by the writer a slight citrate reaction -occurred in a youth who acted as blood donor. The transfusion was -carried out by a modification of the syringe method, which involved -the injection at intervals of a syringeful of citrate solution into -the donor’s circulation. The possibility that the reaction was -produced by another factor was therefore not present in this instance. - -Nevertheless, it must be admitted that citrate has not yet been -absolutely proved to be the cause of this slight reaction in all -the cases in which it occurs. Evidence has, indeed, been brought -forward by Lewisohn and by Meleney to show that citrate is definitely -not responsible for the reaction. The statement is made that some -reaction occurs after 10 per cent. of all transfusions, and that this -percentage is unaffected whether whole blood or citrated blood is -used. Lewisohn has himself investigated the effects in a long series -of parallel cases in which different methods were employed, and he -reports that the results following the use of citrated blood were as -good as with any other method. Drinker states that reactions follow -the use of citrated blood slightly more often than they do that of -whole blood, but this has not been confirmed. He was unable to find -any impurity in the citrate that might be held responsible. It is -quite possible that all the reactions observed are in reality caused -by the “minor agglutinins” mentioned on p. 73. Meleney has noticed -that the blood of some donors is more likely to produce a reaction -than that of others; this suggests that the responsibility rests -with the blood and not with the citrate. The occurrence of a toxic -reaction constitutes the only real objection to the use of citrated -blood that has yet been brought forward, but even this has not yet -been fully substantiated; in any case, the reaction is of so little -importance that it is greatly outweighed by the numerous advantages -that are conferred by the use of citrate. The possibility that a -citrate reaction does sometimes occur may be taken as an indication -in favour of using the smaller amount recommended by Lewisohn rather -than the larger dose used by Robertson. The experience of a great -many observers has established the fact that citrated blood is quite -as effective as whole blood in its therapeutic effects. - -It is convenient to have the sodium citrate in a form ready for -immediate use. I have therefore been in the habit of keeping it -in the solid form in small stoppered bottles, each containing 1 -gramme of the salt. These are sterilized at 130° C., and can be -kept indefinitely until wanted. If 450 cc. of blood or less are to -be drawn, the contents of one bottle is shaken into the transfusion -flask; 50 cc. (approximately 2 oz.) of sterile warm water are added, -in which the citrate will rapidly dissolve. If more than 450 cc. of -blood is to be used, the contents of two bottles must be dissolved in -100 cc. or 4 ozs. of water. Alternatively a concentrated solution of -citrate may be kept in sealed ampoules, but the salt is less stable -in solution, and I prefer to keep it in the solid form. - -The ideal method of blood transfusion seems to me to require that -it shall be absolutely certain of success, that the blood shall -not necessarily be injected into the patient immediately it has -been drawn, so that other circumstances besides the demands of the -transfusion operation can be considered, and that no injury shall be -done to the donor beyond the puncturing of a vein. In addition to -this, the method should be so simple and free from special apparatus -that it can be easily learnt and carried out by one operator without -skilled assistance. All these requirements are fulfilled by the -citrate method, and a satisfactory method of performing this will -next be described. As will be seen, the blood can be drawn with the -minimum amount of injury to the donor; when drawn, it can be put -on one side, for several hours if necessary, and then given to the -patient at whatever may be judged to be the most favourable moment; -the whole process can be carried out by a single operator without -any assistance; and finally, but little practice is needed to make -success certain every time. - -The transfusion apparatus known as “Robertson’s bottle,” first -described by Oswald Robertson in 1918, is the basis of most citrate -methods. This could be easily improvised in a field laboratory, and -was extensively used during the last year of the war. The apparatus -consisted of a glass bottle of about a litre capacity, the mouth -of which was closed by a rubber bung. Through the bung three glass -tubes passed. One, connected by a short rubber tube with a wide-bore -needle, ended about an inch from the bottom of the bottle; through -this the blood flowed into the bottle. A second tube, which reached -to the angle between the side and the bottom of the bottle, was -connected by a rubber tube with a cannula; through this the blood was -injected into the patient. The third tube reached only just beyond -the bung, and to this was attached a Higginson’s syringe, by means of -which either negative or positive pressure would be produced inside -the bottle, according to which end of the syringe was attached. - -It is unnecessary to describe this apparatus any further, for it was -found by myself and others that it could be with advantage modified -in the direction of simplicity. It is in the first place unnecessary -in drawing the blood to create any negative pressure if a needle of -a large enough bore (2 or 3 mm.) be used, and, further, it is an -advantage not to have the needle attached in any way to the bottle, -which, as the blood flows into it, has to be freely agitated in order -to mix the blood quickly with the citrate. The needle may, therefore, -be attached to a rubber tube of suitable length which hangs freely -into the collecting vessel as shown in the diagram on p. 127. The -third tube of “Robertson’s bottle” may be dispensed with by using a -conical flask provided with a side tube to which a rubber bellows -can be attached. The delivery tube is therefore the only one that -need pass through the rubber bung. This tube should have an angle in -it inside the flask so that its lower end reaches into the corner, -and the extremity should be ground down obliquely so that, although -it reaches right into the corner, it does not become occluded by -too accurate contact with the surface of the vessel. By this means -any wastage of blood is prevented. I have found it a very great -convenience to introduce into the delivery tube just outside the -flask an air-lock,[8] the value of which will be seen shortly. To the -barrel of this air-lock a rubber tube with a cannula is attached. -Close to the cannula is some form of clip. The whole apparatus is -illustrated in the figure on p. 133, and with the help of this its -use may be readily understood. - -[Illustration: Fig. 9.--TRANSFUSION NEEDLE (ACTUAL SIZE)] - -The particular form of needle which I have been in the habit of using -is shown in the figure. Its lumen has a diameter of 2 mm., and the -steel tube ends off flush with the wide shoulder to which the rubber -tube is attached. This avoids any recess within the needle in which -clotting may begin. The point of the needle should not be too long, -in order that it may not wound the opposite side of the vein when it -has been introduced. For ease of introduction, however, the extremity -should be very sharp and should have cutting edges. The point and -edges should be touched up on a bevelled hone each time before the -needle is used. The needle should be kept ready for immediate use -in liquid paraffin. I have found that the most convenient way of -keeping it is to put it into a test-tube containing paraffin, which -is plugged with cotton-wool and sterilized at 130° C. in the hot -air oven or by careful heating over a flame. In this way the needle -may be kept ready for an indefinite time without any chance of its -rusting. When it is taken out of the test-tube, a sterile rubber tube -is slipped on to it and it is then ready for use. As an additional -precaution, a small quantity of paraffin may be drawn up into the -rubber tube, which is thus lubricated on the inside, but this is not -absolutely necessary. The tube must be sterilized with the rest of -the apparatus, as rubber is destroyed by liquid paraffin. - -[Illustration: Fig. 10.--DRAWING BLOOD FOR TRANSFUSION] - -When the donor’s arm has been congested by gripping it above the -elbow, or better by the application of a tourniquet[9] drawn to the -requisite degree of tightness, a suitable vein, usually the median -basilic, is chosen. The area of puncture is washed with ether and -a very small quantity, 2 to 3 minims, of 2 per cent. novocain is -introduced over the vein with a hypodermic syringe. If a larger -quantity is used, the vein may become obscured, but this small amount -may be dispersed by a few moments’ pressure with the finger, and is -usually enough to anæsthetize the very small area of skin that is -to be operated upon. A tiny cut in the skin is then made with the -point of a scalpel, and the needle is pushed through into the vein. -If the donor’s vein is a large one, such as is usually found in the -type of donor recommended in a previous chapter, this is quite easy -to do. To make it equally easy if the vein be smaller, it has been -suggested by Watson that the vein may be fixed by pushing an ordinary -fine sewing-needle through the skin at right angles to the line of -the vein, into the vein, and out again through the skin. This needle -is held with the forefinger and thumb of the left hand, while the -right hand pushes the transfusion needle into the lumen of the vein -just below it. When the needle is in the vein, the blood flows out -rapidly through the tube which hangs into the flask containing the -citrate, as illustrated. This flask is held by an assistant, who -mixes the blood with the citrate by gently swinging it. If a properly -adjusted tourniquet is kept on the donor’s arm while he works his -forearm muscles by clasping and unclasping his hand, a flow of blood -is obtained which is fast enough to prevent clotting in the needle, -and indeed is quite as fast as most donors can tolerate. Blood up to -1,000 cc. may be collected in this way in ten to twenty minutes. If -the vein be of a good size, it makes no difference whether the needle -be inserted towards the heart or away from it. When enough blood has -been collected, the tourniquet is removed, the needle is withdrawn, -and pressure is maintained with a sterile swab over the site of -puncture for a few minutes. No further bleeding will take place after -this, and no suture is needed. The donor’s part in the operation is -then finished. He should be made to lie on his back for a few hours -afterwards, and given plenty of fluids, but beyond this no special -precautions are necessary. - -When the blood has been drawn, and has been satisfactorily mixed with -the citrate, the flask may be put on one side until it is wanted, its -mouth having been closed with a cotton-wool stopper. If the blood is -wanted at once, the flask may be stood in a basin of warm water to -keep it at body temperature. Otherwise it may be allowed to cool, and -can be warmed up again when it is to be administered. The citrated -blood may be kept for a considerable time without undergoing any -appreciable change in its therapeutic value. It has been given twelve -hours or more after being taken with the same good effects as if it -had been newly drawn. During the war advantage was taken of this fact -to anticipate during quiet times the necessity for many transfusions -during times of stress. The blood was drawn in some quantity and kept -for several hours in an ice chest, so that it was readily available -during the expected battle. Recently I have administered to a woman -who had been operated upon for a ruptured ectopic gestation 600 cc. -of citrated blood which had been kept for twenty-seven hours at -room temperature after it was drawn. The effect was in every way as -satisfactory as if it had been freshly drawn, and there was no sign -of any toxic reaction. So far as I know, blood had not ever been kept -so long as this before being used, but there does not seem to be any -objection to so doing. - -When the blood is to be given, the delivery tube with the rubber bung -is inserted in the flask, and the corpuscles which have gravitated to -the bottom are distributed again through the fluid by gently shaking -it. In administering the blood, it is very often advisable to inject -it through a cannula which is tied into a vein. If the patient is a -woman, it will usually be found that the veins are small and buried -in fat. Also many transfusions will be given to combat the collapse -due to shock and hæmorrhage, in which case the veins will be empty -and the use of a cannula will be found essential. Sometimes, however, -the patient will have large veins which can be readily distended; -this may sometimes be encouraged by keeping the arm for half an hour -beforehand in a bath of hot water. Under these circumstances the -blood can be given through a needle introduced in exactly the same -way as has already been described in the case of the donor. In the -following account of the process it will be assumed that the use of a -cannula is necessary. - -When choosing a vein in the patient, the operator must be guided -by circumstances. Usually the median basilic will be the most -convenient, and if, in a collapsed patient, this is invisible, -previous knowledge of the position of the vein must determine -the site of the incision. If another operation is being done -simultaneously upon the upper part of the patient’s body, it may -be more convenient to use the internal saphenous vein in Scarpa’s -triangle, or even one of the superficial veins about the ankle. In -administering blood to an infant, several methods have been used. -These are described separately at the end of the present chapter. - -[Illustration: Fig. 11.--TRANSFUSION CANNULA (ACTUAL SIZE)] - -Whatever vein be chosen, the line of the incision is first -infiltrated with a small quantity of a 2 per cent. solution of -novocain. The vein is then dissected out, and is ligatured near the -lower end of the incision. A ligature is also put loosely round -the upper part. The operator now takes the barrel of the air-lock, -which, together with the attached rubber tube and cannula, is filled -with 0·9 per cent. saline solution, all air bubbles being carefully -excluded. The tube is clipped near the cannula, so that the whole -system, including the cannula, remains filled with the fluid. The -form of the cannula used will depend upon the operator’s particular -preference, but a type which I have found very convenient is shown -in the accompanying figure. It is made of glass, and its extremity -is ground down at an angle, which makes it very easy to introduce -into the vein. The slight constriction near this end ensures that -it can be securely tied into the vein and that no leakage round it -shall occur. This is very necessary, because there is sometimes a -considerable pressure to be overcome, due to venospasm in a collapsed -patient, before the blood begins to flow. - -An oblique cut is now made in the vein, as shown in the -illustration, the cannula is introduced, and the upper ligature is -tied. - -[Illustration: Fig. 12.--INSERTION OF THE CANNULA IN A VEIN] - -The barrel of the air-lock, with its contained saline solution, -is then fixed firmly on to the rubber bung, so that the nozzle of -the delivery tube projects into the saline solution. Meanwhile, an -assistant has fixed a rubber bellows on to the side tube of the -flask; a short piece of glass tubing loosely packed with cotton-wool -should be interposed between the bellows and the flask to prevent any -particles of dust being blown over into the flask from the bellows, -which is not sterilized. The clip near the cannula is released, and -some positive pressure is produced inside the flask by means of the -bellows. The citrated blood then rises in the delivery tube, and -a corresponding quantity of saline solution is displaced from the -air-lock into the patient’s circulation. The blood then flows from -the nozzle of the delivery tube into the air-lock, and the remainder -of the saline solution is driven on into the patient. Finally the -blood flows steadily through the cannula, and the rate at which it is -flowing can be observed in the air-lock. - -The presence of this air-lock facilitates, as has been seen, the -introduction of the cannula, into the vein, since there is no leakage -of blood to obscure the operation. In addition, the operator can -see at a glance whether the blood is flowing in properly, and can -regulate the rate of flow to a nicety by varying the pressure in the -flask by means of the bellows. If a very slow injection is required, -the blood can even be made to run drop by drop. If the patient is -suffering from acute anæmia, the blood can be pumped in rapidly, 750 -cc. of blood being given in the course of twenty minutes. If, on the -other hand, the patient has a plethora of fluids, such as is seen in -some cases of secondary anæmia, the blood must be given very much -more slowly than this, since it is dangerous rapidly to increase the -blood volume. A half to three-quarters of an hour must be occupied in -giving 500 cc., and even then the patient may complain of a sensation -of tightness in the chest and of dyspnœa, due to embarrassment of -the right heart during the transfusion. This complaint, however, is -usually transient, and will disappear quickly if the injection be -stopped for a few minutes. - -It has been said that the lower end of the delivery tube reaches -into the angle between the side and the bottom of the flask. When -therefore the flask is nearly empty, it should be tilted so that very -nearly the whole of the blood can be forced up the tube. When the -flask is quite empty, the blood in the barrel of the air-lock must -be carefully watched, and when its level has fallen to the bottom of -this, the clip must be applied to the tube above the cannula. By this -means no blood is wasted except the small quantity which remains in -the tube below the air-lock. As soon as the tube has been clipped the -cannula is withdrawn, the vein is ligatured above the opening into -its lumen, and the edges of the skin incision are sutured. - -Transfusions carried out in this way can be performed with uniform -success. The technique is simple and straightforward at every stage, -and can be easily demonstrated and learnt. It is, in addition, -a perfectly clean process, and not a single drop of blood need -be spilt. Any method which involves the injection of blood under -pressure is open to the objection that it is possible to overlook -the fact that the flask has been emptied and to kill the patient -by injecting air into his veins. This can, however, only happen as -the result of great carelessness on the part of the operator. The -presence of the air-lock affords an additional safeguard, as it can -hardly escape the operator’s notice that blood has ceased to flow -from the nozzle of the delivery tube. - -[Illustration: Fig. 13.--INJECTION OF THE BLOOD, SHOWING USE OF -AIR-LOCK] - -The method may also be criticized on the ground that some damage is -caused to the corpuscles of the donor’s blood by the shaking which is -necessary to mix it with the citrate solution. This objection is, -in my opinion, theoretical rather than practical. If, however, it be -desired to avoid any such shaking, the apparatus designed by A. E. -Stansfeld and described by him in 1918 may be used. This ensures that -the citrate and the blood flow into the containing vessel together, -so that no further mixing is needed. The apparatus is more cumbrous, -more fragile, and less easy to clean and to sterilize than that -described above. In the hands of an expert it will give excellent -results, but its use requires some little practice, and it is -therefore not so well adapted for general use. - -The whole of my own apparatus, as described above, may be obtained -from Messrs. Allen & Hanburys, Wigmore Street, London, W.1, who also -provide a convenient box for carrying it. - - -=Transfusion of Infants.=--The technique of transfusions performed -upon children over the age of about four years does not differ from -that used for adults, except that less blood is to be given. The -antecubital veins are much smaller and a finer cannula may have to -be used, but this is the only source of trouble. The transfusion of -infants and very young children may, however, be found to be much -more difficult. The operation will have to be done for conditions -such as melæna neonatorum, which was discussed on p. 48 of the -present work, or for post-operative collapse, such as may follow an -operation for congenital hypertrophic stenosis of the pylorus, for -intussusception, or for some of the more extreme cases of harelip -and cleft palate. In all such instances the transfusion will be a -matter of some urgency. Speed and certainty will depend on previous -knowledge of the best method to be employed. - -In the case of melæna neonatorum treated by R. D. Laurie, which has -been already referred to, a needle was introduced into one of the -antecubital veins, and 20 cc. of citrated blood were injected with a -syringe. This method, however, is not to be recommended, on account -of its great difficulty. - -The method used by Helmholtz and also by Howard depends on the -introduction of a syringe needle into the superior longitudinal -sinus through the anterior fontanelle. A needle two to three inches -long attached to a 20 cc. syringe is inserted near the upper angle -of the fontanelle at an angle of about 25° with the scalp. As the -needle pierces the wall of the sinus, a sensation of resistance is -experienced, similar to that given by the piercing of the dura mater -in doing a lumbar puncture. Blood should then be allowed to enter -the syringe in order to demonstrate that the point of the needle -really is lying in the sinus. Abnormalities have occasionally been -met with, in which the sinus was situated to one side of the middle -line or was very much smaller than usual. The danger of injecting -the blood in such a case into the brain or the subdural space need -not be emphasized. Difficulty may also be caused by restlessness on -the part of the child, and to overcome this Helmholtz has devised an -apparatus which grips and fixes the child’s head at a suitable angle. -All this, however, makes the process unnecessarily elaborate. As an -alternative, Vincent has exposed one of the internal jugular veins -into which he introduces a cannula. This again is a comparatively -difficult operation, which may leave a permanent scar in a -conspicuous place. Vincent had previously used the femoral vein, but -he found this difficult to approach, and the wound was apt to become -contaminated afterwards. - -The method of choice is undoubtedly that used by Bruce Robertson, -who has performed a much larger number of transfusions upon infants -and children than any other worker in this field of surgery. He has -found that the internal saphenous vein near the ankle is a vessel -possessing a fairly wide lumen and thick walls even in infants, so -that a needle or cannula can be introduced into it with comparative -ease and rapidity. The vein must, of course, be freely exposed -through an incision, but its situation removes any objection there -might otherwise be to this operation. Robertson has usually employed -the syringe-cannula method described earlier in the present chapter, -but there is no objection to the use of an anticoagulant. The small -amount of blood to be given, 15 cc. per pound of body weight, makes -the use of the transfusion flask unnecessary. It is better to use a -20 cc. syringe, into which 2 cc. of a 10 per cent. solution of sodium -citrate is drawn as a preliminary. The needle in the donor’s vein and -the cannula in the infant’s saphena should each be provided with a -rubber connexion, which can be clipped, or pinched by an assistant, -when the syringe is not attached. The syringe containing the citrate -is filled with blood and injected into the infant as often as may be -necessary until the total amount decided upon has been given. - -Robertson has used this method for complete replacement of the -circulating blood in treating streptococcal septicæmia following -erysipelas, and for shock in children due to burns. The infant’s -blood is removed through the anterior fontanelle, while a fresh -supply is injected into the saphenous vein. Complete replacement -has not, so far as I know, ever been performed upon an adult, but -the process is feasible, given a large enough assemblage of donors. -In this way some _vieillard_ might attempt the rejuvenation, -which at present, as we are told, has only been obtained from the -transplantation of “monkey glands” by Viennese professors. - - - - -BIBLIOGRAPHY - - - 1. ADDIS, T.: “The effect of intravenous injections of fresh human - serum and of phosphated blood on the coagulation time of the blood - in hereditary hæmophilia.” _Proc. Soc. Exp. Biol. and Med._, 1916, - xiv. 19. - - 2. AGOTE, L.: “Nuevo procedimiento para la transfusión del sangre.” - _Anales del Inst. modelo de clin. med._ Buenos Ayres, Jan. 1915. - - 3. ALBINI: “Relazione sulla trasfusione diretta di sangue - d’agnello.” Naples, 1873. - - 4. ALEXANDER, W.: “An enquiry into the distribution of the blood - groups in patients suffering from malignant disease.” _Brit. Journ. - Exp. Path._, 1921, ii. 66. - - 5. 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COX, T.: “An account of another experiment of transfusion, viz. - of bleeding a mangy into a sound dog.” _Philosophical Trans._, - 1667, ii. 451. - - 58. CRILE, G. W.: “The technique of direct transfusion of blood.” - _Ann. Surg._, 1907, xlvi. 329. - - 59. CRILE, G. W.: “Hæmorrhage and transfusion.” Appleton & Co., - N.Y., 1909. - - 60. CROTTI, A.: “Indirect transfusion of blood.” _Surg. Gynec. and - Obstet._, 1914, xviii. 236. - - 61. CULPEPPER, W. L.: “Report on five thousand bloods typed, using - Moss’s grouping.” _Journ. Lab. and Clin. Med._, 1921, vi. 276. - - 62. CURCHOD, H.: “Transfusion of blood.” _Rev. méd. de la Suisse_. - Rome, 1920, xl. 666. - - 63. CURTIS, A. H., & DAVID, V. C.: “Transfusion of blood by a new - method, allowing accurate measurement.” _Journ. Am. Med. Assoc._, - 1911, lvi. 35. - - 64. DALE, H. H., and others: “Surgical shock and some allied - conditions.” _Brit. Med. Journ._, 1917, i. 381. - - 65. DALE, H. H., and others: “Traumatic toxæmia as a factor in - shock.” _Rep. of the Med. Res. Com._, viii., March 1919. - - 66. DARWIN, ERASMUS: “Zoonomia; or the Laws of Life.” London, 1794. - 2 vols., 4^o. Vol. i. p. 373; vol. ii. pp. 120, 605, 676. - - 67. DAVID, V. C., & CURTIS, A. H.: “Experiments in the treatment - of acute anæmia by blood transfusion and by intravenous saline - infusion.” _Surg. Gyn. and Obstet._, 1912, xv. 476. - - 68. DAVID, V. C., & CURTIS, A. H.: “Recent experiences with blood - transfusion.” _Journ. Am. Med. Assoc._, 1914, lxii. 775. - - 69. DAWSON, P. M.: “The changes in the heart rate and blood - pressures resulting from severe hæmorrhage and subsequent infusion - of sodium bicarbonate.” _Journ. Exp. Med._, 1905, vii. 1. - - 70. DENYS, J.: “A letter concerning a new way of curing sundry - diseases by transfusion of blood.” _Philosophical Trans._, 1667, - ii. 489. - - 71. DENYS, J.: “An extract of a letter touching a late cure of an - inveterate phrensy by the transfusion of blood.” _Philosophical - Trans._, 1667, ii. 617. - - 72. DIEFFENBACH, J. F.: “Die Transfusion des Blutes und die - Infusion der Arzneien in Blutgefässe.” Berlin, 1828. - - 73. DIJK, H. VAN: “Malaria induced by convalescent’s serum.” - _Nederl. Tijdschr. v. Geneesk._, 1920, ii. 1181. - - 74. DORRANCE, G. M.: “Indications for blood transfusion.” _Am. - Journ. Med. Sci._, 1917, cliv. 216. - - 75. DORRANCE, G. M., & GINSBURG, N.: “Transfusion: history, - development, present status and technique of operation.” _N.Y. Med. - Journ._, 1908, lxxxvii. 941. - - 76. DRINKER, C. R., & BRITTINGHAM, H. H.: “The cause of the - reactions following transfusion of citrated blood.” _Arch. Int. - Med._, 1919, xxiii. 133. - - 77. DRUMMOND, H., & TAYLOR, E. S.: “The use of intravenous - injections of gum acacia in surgical shock.” _Rep. of the Med. Res. - Com._, iii., 1919, 135. “Observations on the blood pressure in gas - gangrene infection.” _Ibid._, v. 1919, 199. - - 78. DUKE, W. W.: “Variation in the platelet count.” _Journ. Am. - Med. Assoc._, 1915, lxv. 1600. - - 79. DUNGERN, E. VON, & HIRSCHFELD, L.: “Ueber Nachweis - und Vererbung biochemischer strukturen.” _Zeitschr. f. - Immunitätsfschng._, 1910, iv. 531; 1911, viii. 526. - - 80. DUNGERN, E. VON, & HIRSCHFELD, L.: “Ueber Vererbung - gruppenspezifischer strukturen des Blutes.” _Ibid._, 1910, vi. 284. - - 81. DUNGERN, E. VON, & HIRSCHFELD, L.: “Ueber die Giftigkeit - des Blutes nach der Injektion protoplasmatischen Substanzen und - während der Schwangerschaft, und über passive Allergie gegenüber - Hodensubstanzen.” _Ibid._, 1911, viii. 332. - - 82. EBERLE, D.: “Transfusion and reinfusion of blood.” _Schweiz. - med. Wchnschr._, 1920, l. 961. - - 83. ELSBERG, C. A.: “A simple cannula for the direct transfusion of - blood.” _Journ. Am. Med. Assoc._, 1909, lii. 887. - - 84. ELY, A. H., & LINDEMAN, E.: “Acidosis complicating pregnancy. - Report of a case cured by transfusion.” _Am. Journ. Obstet. and - Dis. Wom. and Child._, July, 1916, lxxiv. 42. - - 85. EMSHEIMER, H. W.: “Intramuscular injections of whole blood in - the treatment of purpura hæmorrhagica.” _Journ. Am. Med. Assoc._, - 1916, lxvi. 20. - - 86. EPSTEIN, A. A., & OTTENBERG, R.: “A method for agglutination - tests.” _Arch. Int. Med._, 1909, iii. 286. - - 87. ERLANGER, J., & GASSER, H. S.: “Hypertonic gum acacia and - glucose in the treatment of secondary traumatic shock.” _Ann. - Surg._, 1919, lxix. 389. - - 88. FLEMING, A., & PORTEOUS, A. B.: “Blood transfusion by the - citrate method.” _Lancet_, 1919, i. 973. - - 89. FLÖRCKEN, H.: “Zur Frage der direkten Bluttransfusion durch - Gefässnaht.” _Zentrbl. f. Chir. Leipzic_, 1911, xxxviii. 305. - - 90. FOLLI, FRANCESCO: “Stadera medica, nella quale oltre la - medicina infusoria, ed altre novita, si bilanciano le ragioni - favore voli e le contrarie alla trasfusione del sangue.” Florence, - 1680. - - 91. FORSIUS, R.: “Severe hæmophilic intestinal hæmorrhage treated - with transfusion of blood.” _Finska Läkaresällskapets Handl._, - 1915, lvii. No. 3. - - 92. FRANK, R. T., & BAEHR, G.: “A new method for the transfusion of - blood. An experimental study.” _Journ. Am. Med. Assoc._, 1909, lii. - 1746. - - 93. FRASER, J., & COWELL, E. M.: “A clinical study of the blood - pressure in wound conditions.” _Report of the Med. Res. Com._, ii. - (1), 1919, 49. - - 94. FREILICH, E. B., and others: “Blood transfusion in treatment of - pulmonary tuberculosis.” _Illin. Med. Journ._, 1921, xxxix. 32. - - 95. FREUND, H. A.: “A method for the transfusion of fresh normal - blood.” _Journ. Michigan Med. Soc._, 1913, xii. 459. - - 96. FRY, H. J. B.: “The use of immunized blood donors in the - treatment of pyogenic infections by whole blood transfusions.” - _Brit. Med. Journ._, 1920, i. 290. - - 97. FRYER, B. E.: “A few remarks on the transfusion of blood, with - a modification of the apparatus of Aveling.” _Med. Rec._, 1874, ix. - 201. - - 98. FULLERTON, A., DREYER, G., & BAZETT, H. C.: “Direct transfusion - of blood, with a description of a simple method.” _Lancet_, 1917, - i. 715. - - 99. GARBAT, A. L.: “Intravenous injections of sodium citrate.” - _Journ. Am. Med. Assoc._, 1916, lxvi. 1543. - - 100. GESELLIUS, F.: “Die Transfusion des Blutes.” St. Petersburg, - 1873. - - 101. GESELLIUS, F.: “Zur Thierblut-Transfusion beim Menschen.” St. - Petersburg, 1874. - - 102. GETTLER, A. O., & LINDEMAN, E.: “A new method of acidosis - therapy. Blood transfusion from an alkalinized donor, with report - of case.” _Journ. Am. Med. Assoc._, 1917, lxviii. 594. - - 103. GIFFIN, H. Z.: “A report on the treatment of pernicious anæmia - by transfusion and splenectomy.” _Journ. Am. Med. Assoc._, 1917, - lxviii. 429. - - 104. GRAHAM, J. M.: “Observations on the technique of blood - transfusion.” _Edin. Med. Journ._, 1919, xxiii. 358. - - 105. GRAHAM, J. M.: “Transfusion of blood in cases of hæmorrhage.” - _Edinb. Med. Journ._, 1920, xxiv. 142. - - 106. GRAHAM, J. M.: “Transfusion of blood in pernicious anæmia.” - _Edinb. Med. Journ._, 1920, xxiv. 282. - - 107. GRUTZ, O.: “Bluttransfusion bei Morbus maculosus Werlhofi.” - _Berl. Klin. Wchnschr._, 1921, lviii. 53. - - 108. GUIOU, N. M.: “Blood transfusion in a field ambulance.” _Brit. - Med. Journ._, 1918, i. 695. - - 109. GURYE, G. DE: “An account of more tryals of transfusion, - accompanied with some considerations thereon, chiefly in reference - to its cautious practice on Man; together with a farther - vindication of this invention from usurpers.” _Philosophical - Trans._, 1667, ii. 517. - - 110. HAHN, M.: “Hæmophilia treated by transfusion.” _Med. Rec._, - 1910, lxxviii. 624. - - 111. HALSTED, W. S.: “Refusion in the treatment of carbonic oxide - poisoning.” _Ann. of Anat. and Surg._, 1884, Jan. - - 112. HAPP, W. M.: “Appearance of iso-agglutinins in infants and - children.” _Journ. Exp. Med._, 1920, xxxi. 313. - - 113. HARDING, M. E.: “The toxæmic stage of diphtheria.” _Lancet_, - 1921, i. 737. - - 114. HARRIS, D. T.: “The value of the vital-red method as a - clinical means for the estimation of the volume of the blood.” - _Brit. Journ. Exp. Path._, 1920, i. 142. - - 115. HARTWELL, J. A.: “A simple method of blood transfusion with - cannula.” _Journ. Am. Med. Ass._, 1909, lii. 297. - - 116. HARTWELL, J. A.: “A consideration of the various methods of - blood transfusion and its value.” N.Y. _State Journ. Med._, 1914, - xiv. 535. - - 117. HASSE, O.: “Report on twelve cases of the direct transfusion - of lamb’s blood.” _Allgem. Wiener Medizin. Zeit._, Dec. 1873. - (Abstracted in the _Lond. Med. Rec._, Dec. 31, 1873.) - - 118. HÉDON, E.: “Note complémentaire sur la transfusion du sang - citraté.” _Presse méd._, 1918, xxvi. 57. - - 119. HEKTOEN, L.: “Iso-agglutination of human corpuscles.” _Journ. - Infect. Dis._, 1907, iv. 297. - - 120. HELMHOLZ, H. F.: “The longitudinal sinus as the place of - preference in infancy for intravenous aspirations and injections, - including transfusion.” _Am. Journ. Dis. of Children_, 1915, x. 194. - - 121. HICKS, J. BRAXTON: “Cases of transfusion, with some remarks - on a new method of performing the operation.” _Guy’s Hosp. Rep._, - 1869, 3rd s., xiv. 1. - - 122. HIGGINSON, A.: “Report of seven cases of transfusion of blood, - with a description of the instrument invented by the author.” - _Liverpool Med. Chir. Journ._, 1857, i. 102. - - 123. HINDSE-NIELSEN: “Nitro-benzol poisoning treated with blood - transfusion.” _Ugeskift f. Laeger_, 1920, Sept. 9. - - 124. HIRSCHFELD, L., & HIRSCHFELD, H.: “Serological differences - between the blood of different races.” _Lancet_, 1919, ii. 675. - - 125. HOFFMAN, M. H., & HABEIN, H. C.: “Transfusion of citrated - blood.” _Journ. Am. Med. Assoc._, 1921, lxxvi. 358. - - 126. HOOKER, R. S.: “The treatment of staphylococcus septicæmia by - transfusion of immune blood.” _Ann. Surg._, 1917, lxvi. 513. - - 127. HOWARD, W. S.: “A simple method of transfusion in hæmorrhage - of the new-born, with report of a case.” _Journ. Am. Med. Assoc._, - 1915, lxv. 1365. - - 128. HUCK, F. G.: “Changes in the blood immediately following - transfusion.” _Johns Hopkins Hosp. Bull._, 1919, xxx. 63. - - 129. HULL, A. J.: “Direct transfusion of blood.” _Brit. Med. - Journ._, 1917, ii. 683. - - 130. HUNT, E. L., & INGLEBY, H.: “A case of peptic ulcer with grave - anæmia treated by intravenous injection of whole blood.” _Lancet_, - 1919, i. 975. - - 131. HUNT, V. C.: “Reaction following blood transfusion by the - sodium citrate method.” _Texas State Journ. Med._, 1918, xiv. 192. - (Also in _Collected Papers of the Mayo Clinic_, x. 1918.) - - 132. HUSTIN: “Principe d’une nouvelle méthode de transfusion - muqueuse.” _Journ. méd. de Brux._, 1914, xii. 436. - - 133. HUTCHISON, R.: “Three cases of melæna neonatorum successfully - treated by the injection of whole blood.” _Brit. Med. Journ._, - 1917, ii. 617. - - 134. HÜTER, C.: “Ein Fall von Kohlenoxydvergiftung; Heilung durch - Transfusion.” _Berl. Klin. Wchnschr._, 1870, vii. 341. - - 135. INGEBRIGTSEN, R.: “The influence of iso-agglutinins on the - final results of homoplastic transplantation of arteries.” _Journ. - Exp. Med._, 1912, xvi. 169. - - 136. JANEWAY, H. H.: “An improved device for transfusion.” _Ann. - Surg._, 1911, lxiii. 720. - - 137. JANSKY, J.: “Hæmatologische Studien bei psykotiken.” _Klincky - Sborink_, 1907, viii. 85. - - 138. JANSKY, J.: “Recommendation by a committee that the Jansky - classification of blood groups be used in preference to that of - Moss on grounds, of priority.” _Journ. Am. Med. Assoc._, 1921, - lxxvi. 130. - - 139. KAHN, A.: “Continuous transfusion. The production of - immunity.” _N.Y. Med. Rec._, 1916, lxxxix. 553. - - 140. KARSNER, H. T.: “Laboratory problems of blood transfusion.” - _Journ. Am. Med. Assoc._, 1921, lxxvi. 88. - - 141. KEATOR, H. M.: “Transfusion in case of toxæmia of early - pregnancy with unusual hæmorrhagic manifestations.” _Am. Journ. - Obstet. and Dis. Wom. and Child_, 1912, lxv. 1003. - - 142. KEITH, N. M.: “Blood volume changes in wound shock and primary - hæmorrhage.” _Rep. of the Med. Res. Com._, ix., March, 1919. - - 143. KEITH, N. M., ROWNTREE, L. G., & GERAGHTY, J. T.: “A method - for the determination of plasma and blood volume.” _Arch. Int. - Med._, 1915, xvi. 547. - - 144. KEYNES, G. L.: “Blood transfusion: its theory and practice.” - _Lancet_, 1920, i. 1216. - - 145. KIMPTON, A. R., & BROWN, J. H.: “A new and simple method of - transfusion.” _Journ. Am. Med. Assoc._, 1913, lxi. 117. - - 146. KIMPTON, A. R.: “Further notes on transfusion by means of - glass cylinders.” _Journ. Am. Med. Assoc._, 1913, lxi. 1628. - - 147. KIMPTON, A. R.: “Transfusion. Experiences in over two hundred - cases.” _Boston Med. and Surg. Journ._, 1918, clxxviii. 351. - - 148. KIMPTON, A. R., & BROWN, J. H.: “Technique of transfusion - by means of glass tubes.” _Bost. Med. and Surg. Journ._, 1915, - clxxiii. 425. - - 149. KING, E.: “An account of an easier and safer way of - transfusing blood out of one animal into another, viz., by the - veins, without opening an artery of either.” _Philosophical - Trans._, 1667, ii. 449. - - 150. KING, E.: “The method of transfusing into the veines of men.” - _Philosophical Trans._, 1667, ii. 522. - - 151. KING, E.: “An account of the experiment of transfusion, - practised upon a man in London.” _Philosophical Trans._, 1667, ii. - 557. - - 152. KING, H. H.: “Direct vein to vein transfusion.” _Brit. Med. - Journ._, 1918, i. 498. - - 153. KUSH, M.: “An automatic transfusion apparatus.” _Journ. Am. - Med. Assoc._, 1915, lxv. 1180. - - 154. LAMBERT, S. W.: “Melæna neonatorum, with report of a case - cured by transfusion.” _N.Y. Med. Rec._, 1908, lxxiii. 885. - - 155. LANDOIS, L.: “Die Transfusion des Blutes.” Berlin, 1866. - Leipzig, 1875. - - 156. LANDSTEINER, K.: “Ueber Agglutinationserscheinungen normalen - menschlichen Blutes.” _Wien. Klin. Wchnschr._, 1901, xiv. 1132. - - 157. LAPAGE, C. P.: “Two cases of melæna neonatorum treated by - injection of fresh citrated blood.” _Proc. Roy. Soc. Med._, 1920, - xiii. Sect. Child. Dis., 158-160. - - 158. LAURIE, R. D.: “Melæna neonatorum treated by blood - transfusion.” _Brit. Med. Journ._, 1921, i. 527. - - 159. LEARMONTH, J. R.: “The inheritance of specific iso-agglutinins - in human blood.” _Journ. Genetics_, 1920, x. 141. - - 160. LEE, R. I.: “A simple and rapid method for the selection of - suitable donors for transfusion by the determination of blood - groups.” _Brit. Med. Journ._, 1917, ii. 684. - - 161. LEISRINK, H.: “Ueber die Transfusion des Blutes.” _Samm. Klin. - Vortr., No. 41._ Leipzig, 1872, 235. - - 162. LESPINASSE, V. D.: “The treatment of hæmorrhagic disease of - the new-born by direct transfusion of blood, with a clinical report - of fourteen personal cases.” _Journ. Am. Med. Assoc._, 1914, lxii. - 1866. - - 163. LESPINASSE, V. D.: “Technique of direct transfusion of blood, - using iridio-platinum tubes.” _Chicago Med. Rec._, 1915, xxxvii. - 589. - - 164. LESSER, L.: “Transfusion and autotransfusion.” _Samml. Klin. - Vortr., No. 86_, Leipzig, 1875. _Inn. Med., No. 29_, p. 665. - - 165. LEVIN, I.: “Plastic surgery of blood vessels and direct - transfusion of blood.” _Ann. of Surg._, N.Y., 1913, May. - - 166. LEWISOHN, R.: “A new and greatly simplified method of blood - transfusion.” _N.Y. Med. Rec._, 1915, lxxxvii. 141. - - 167. LEWISOHN, R.: “Blood transfusion by the citrate method.” - _Surg. Gynec. and Obstet._, 1915, xxi. 37. - - 168. LEWISOHN, R.: “The citrate method of blood transfusion in - children.” _Am. Journ. Med. Sci._, 1915, cl. 886. - - 169. LEWISOHN, R.: “The importance of the proper dosage of sodium - citrate in blood transfusion.” _Ann. of Surg._, 1916, lxiv. 618. - - 170. LEWISOHN, R.: “Modern methods of blood transfusion.” _Journ. - Am. Med. Assoc._, 1917, lxviii. 826. - - 171. LEYTON, O.: “Transfusion in diseases of the blood.” _Brit. - Med. Journ._, 1919, i. 279. - - 172. LIBAVIUS, A.: “Denfensio syntagmatis arcanorum chymicorum.” - Frankfort, 1615, ch. iv., p. 8. - - 173. LIBMAN, E., & OTTENBERG, R.: “A practical method for - determining the amount of blood passing over during direct - transfusion.” _Journ. Am. Med. Assoc._, 1914, lxii. 764. - - 174. LIBMAN, E., & OTTENBERG, R.: “Recent observations on blood - transfusion.” _Tr. Coll. Phys. Phila._, 1917, xxxix. 266. - - 175. LICHTENSTEIN: “Eigenbluttransfusion bei Extrauteringravidität - und Uterusruptur.” _Münch. Med. Wchnschr._, 1915, lxii. 1597. - - 176. LINDEMAN, E.: “Simple syringe transfusion with special - cannulas.” _Am. Journ. Dis. of Children_, 1913, vi. 28. - - 177. LINDEMAN, E.: “Blood transfusion. Report of one hundred and - thirty-five transfusions by the syringe-cannula system.” _Journ. - Am. Med. Assoc._, 1914, lxii. 993. - - 178. LINDEMAN, E.: “Reactions following blood transfusion by the - syringe cannula system.” _Journ. Am. Med. Assoc._, 1916, lxvi. 624. - - 179. LINDEMAN, E.: “The total blood volume in pernicious anæmia.” - _Journ. Am. Med. Assoc._, 1918, lxx. 1292. - - 180. LITTLE, G. F.: “Transfusion of antibacterial blood. Report of - case.” _Journ. Am. Med. Assoc._, 1920, lxxiv. 734. - - 181. LOSEE, J. R.: “Blood transfusion.” _Am. Journ. Med. Sci._, - 1919, clviii. 711. - - 182. LOSEE, J. R.: “Blood transfusion in obstetrics.” _Med. Rec._, - 1920, xcvii. 265. - - 183. LÖWENTHAL, W.: “Ein Beitrag zur Lehre von der Transfusion des - Blutes.” _Berl. Klin. Wchnschr._, 1871, viii. 487. - - 184. LOWER, R.: “The method observed in transfusing the blood out - of one animal into another.” _Philosophical Trans._, 1666, i. 353. - - 185. McCLURE, R. D.: “Pernicious anæmia treated by splenectomy, and - systematic, often-repeated transfusion of blood. Transfusion in - benzol poisoning.” _Journ. Am. Med. Assoc._, 1916, lxvii. 793. - - 186. McCLURE, R. D., & DUNN, G. R.: “Transfusion of blood. History, - methods, dangers, preliminary tests, present status. Report of one - hundred and fifty transfusions.” _Johns Hopkins Hosp. Bull._, 1917, - xxviii. 99. - - 187. McGRATH, B. F.: “A simple instrument for [direct] - transfusion.” _Journ. Am. Med. Assoc._, 1914, lxii. 40. - - 188. McGRATH, B. F.: “Vascular suture in transfusion.” _Journ. Am. - Med. Assoc._, 1914, lxii. 1326. - - 189. McGRATH, B. F.: “A simple apparatus for transfusion by the - aspiration-injection method.” _Surg. Gynec. and Obstet._, 1914, - xviii. 376. - - 190. MADGE, H. M.: “On transfusion of blood.” _Brit. Med. Journ._, - 1874, i. 42. - - 191. MANN, F. C.: “Experimental surgical shock. The treatment of - the condition of low blood pressure, which follows exposure of the - abdominal viscera.” _Am. Journ. Physiol._, 1919, l. 86. (Also in - _Collected Papers of the Mayo Clinic_, 1919, xi. 1225.) - - 192. MARTIN: “Ueber eine mit günstigem Erfolge bei einer - lebensgefährlichem Intrauterinblutung vollzogene Transfusion.” - _Monatschr. f. Geburtsk. u. Frauenk._, 1861, xvii. 269. - - 193. MARTIN: “Iso-agglutination beim Menschen.” _Centralblatt f. - Bact._, 1905, xxxix. 704. - - 194. MELENEY, H. E., STEARNS, W. W., FORTUINE, S. T., & FERRY, R. - M.: “Post-transfusion reactions: a review of 280 transfusions.” - _Am. Journ. Med. Sci._, 1917, cliv. 733. - - 195. MILLER, G. I.: “Blood transfusion, indications and technique.” - _Med. Rec._, 1915, lxxxviii. 425. - - 196. MINOT, G. R.: “Methods for testing donors for transfusion of - blood and consideration of factors influencing agglutination and - hæmolysis.” _Boston Med. and Surg. Journ._, 1916, clxxiv. 667. - - 197. MINOT, G. R., & LEE, R. I.: “The blood platelets in - hæmophilia.” _Arch. Int. Med._, 1916, xviii. 474. - - 198. MINOT, G. R., & LEE, R. I.: “Treatment of pernicious anæmia, - especially by transfusion and splenectomy.” _Bost. Med. and Surg. - Journ._, 1917, clxxvii. 761. - - 199. MOREL, L.: “Transfusion of blood.” _Arch. gen. de Chir._, - 1914, viii. 1. - - 200. MOSS, W. L.: “Studies on iso-agglutinins and iso-hemolysins.” - _Johns Hopkins Hosp. Bull._, 1910, xxi. 63. - - 201. MOSS, W. L.: “Paroxysmal hæmoglobinuria: blood studies in - three cases.” _Johns Hopkins Hosp. Bull._, 1911, xxii. 238. - - 202. MOSS, W. L.: “A simple method for the indirect transfusion of - blood.” _Am. Journ. Med. Sci._, 1914, cxlvii. 698. - - 203. MOSS, W. L.: “A simplified method for determining the - iso-agglutinin group in the selection of donors for blood - transfusion.” _Journ. Am. Med. Assoc._, 1917, lxviii. 1905. - - 204. NIX, J. T.: “Blood transfusion simplified. Deductions from - nineteen cases, eleven human and eight on dog.” _New Orleans Med. - and Surg. Journ._, 1916, lxix. 435. - - 205. OEHLECKER, F.: “Bluttransfusion von Vene zu Vene mit Messung - der übertragenen Blutmenge.” _Zentralbl. f. Chir._, 1919, xlvi. 17. - - 206. OEHLECKER, F.: “Direkte Bluttransfusion von Vene zu Vene bei - perniziöse Anæmie.” _München. Med. Wchnschr._, 1919, lxvi. 895. - - 207. ORÉ: “Études historiques et physiologiques sur la transfusion - du sang.” Paris, 1868. - - 208. OTTENBERG, R.: “Transfusion and arterial anastomosis.” _Ann. - Surg._, 1908, xlvii. 486. - - 209. OTTENBERG, R.: “Transfusion and the question of intravascular - agglutination.” _Journ. of Exp. Med._, 1911, xiii. 425. - - 210. OTTENBERG, R.: “The effect of sodium citrate on blood - coagulation in hæmophilia.” _Proc. Soc. for Exp. Biol. and Med._, - 1916, xiii. 104. - - 211. OTTENBERG, R.: “Medico-legal applications of human blood - grouping.” _Journ. Am. Med. Assoc._, 1921, lxxvii. 682. - - 212. OTTENBERG, R., & FRIEDMAN, S. S.: “The occurrence of grouped - iso-agglutination in the lower animals.” _Journ. Exp. Med._, 1911, - xiii. 531. - - 213. OTTENBERG, R., & KALISKI, D. J.: “Accidents in transfusion. - Their prevention by preliminary examination. Based on an experience - of 128 transfusions.” _Journ. Am. Med. Assoc._, 1913, lxi. 2138. - - 214. OTTENBERG, R., KALISKI, D. J., & FRIEDMAN, S. S.: - “Experimental agglutinative and hemolytic transfusions.” _Amer. - Journ. Med. Res._, 1913, xxviii. 141. - - 215. OTTENBERG, R., & LIBMAN, E.: “Blood transfusion; indications; - results; general management.” _Am. Journ. Med. Sci._, 1915, cl. 36. - - 216. OTTENBERG, R., & THALIMER, W.: “Studies in experimental - transfusion.” _Journ. Med. Res._, 1915-16, xxxiii. 213. - - 217. PANUM, P. L.: “Experimentelle Untersuchungen über die - Transfusion, Transplantation, oder Substitution des Blutes in - theoretischer und praktischer beziehung.” _Virchow’s Arch. f. Path. - Anat._, 1863, xxvii. 240, 433. - - 218. PEMBERTON, J. DE J.: “Blood transfusion.” _Surg. Gynec. and - Obstet._, 1919, xxviii. 262. (Also in _Collected Papers of the Mayo - Clinic_, 1918, x. 508.) - - 219. PEMBERTON, J. DE J.: “Practical considerations of the dangers - associated with blood transfusions.” _Journ. Iowa State Med. Soc._, - 1920, x. 170. (Also in _Collected Papers of the Mayo Clinic_, 1919, - xi. 635.) - - 220. PERCY, N. M.: “A simplified method of blood transfusion, with - report of six cases of pernicious anæmia treated by massive blood - transfusions and splenectomy.” _Surg. Gynec. and Obstet._, 1915, - xxi. 360. - - 221. PETERSON, E. W.: “Purpura hæmorrhagica treated by blood - transfusion.” _Post-Graduate_, N.Y., 1914, xxix. 499. - - 222. PETERSON, E. W.: “Results from blood transfusion in the - treatment of severe post-operative anæmia and the hæmorrhagic - diseases.” _Journ. Am. Med. Assoc._, 1916, lxvi. 1291. - - 223. PÉTREN, G.: “Coagulation time in icterus.” _Beitr. z. Klin. - Chirurg._, 1920, cxx. 501. - - 224. PONFICK: “Experimentelle Beiträge zur Lehre von der - Transfusion.” _Virchow’s Arch. f. Path. Anat._, 1875, lxii. 273. - - 225. POOL, E. H.: “Transfusion and splenectomy for von Jaksch’s - anæmia in an infant.” _Ann. Surg._, March 1915. (In Transact. of - N.Y. Surg. Soc.) - - 226. POOL, E. H., & McCLURE, R. D.: “Transfusion by Carrel’s - end-to-end suture method. With report of cases.” _Ann. Surg._, - 1910, lii. 433. - - 227. POPE, L.: “Simplified transfusion.” _Journ. Am. Med. Assoc._, - 1913, lx. 1284. - - 228. PRIMROSE, A.: “The value of the transfusion of blood in the - treatment of the wounded in war.” _Ann. Surg._, 1918, lxviii. 118. - - 229. PRIMROSE, A., & RYERSON, E. S.: “The direct transfusion of - blood, its value in hæmorrhage and shock and in treatment of the - wounded in the war.” _Brit. Med. Journ._, 1916, ii. 384. - - 230. RAMIREZ, M. A.: “Horse asthma following blood transfusion.” - _Journ. Am. Med. Assoc._, 1919, lxxiii. 984. - - 231. RAMSAY, J.: “Transfusion of blood in nephritis.” _Brit. Med. - Journ._, 1920, i. 766. - - 232. RANSOM, S. H.: “The treatment of staphylococcus septicæmia by - transfusion of immune blood.” _Ann. Surg._, 1917, lxvi. 513. - - 233. RAULSTON, B. O., & WOODYATT, R. T.: “Blood transfusion in - diabetes mellitus.” _Journ. Am. Med. Assoc._, 1914, lxii. 996. - - 234. RICHARDSON, B. W.: “The cause of coagulation of the blood. The - Astley Cooper prize essay for 1856, with additional observations - and experiments.” London, 1858. - - 235. RICHARDSON, E. H.: “Treatment of the emergency cases of - ectopic pregnancy.” _Johns Hopkins Hosp. Bull._, 1916, xxvii. 262. - - 236. ROBERTSON, L. B.: “The transfusion of whole blood.” _Brit. - Med. Journ._, 1916, ii. 38. - - 237. ROBERTSON, L. B.: “A contribution on blood transfusion in war - surgery.” _Lancet_, 1918, i. 759. - - 238. ROBERTSON, L. B.: “Blood transfusion in hæmorrhagic disease of - the new-born.” _Brit. Med. Journ._, 1921, i. - - 239. ROBERTSON, L. B.: “Blood transfusion in severe burns in - infants and young children.” _Canad. Med. Assoc. Journ._, 1921, xi. - 744. - - 240. ROBERTSON, L. B., & WATSON, C. G.: “Further observations on - the results of blood transfusion in war surgery.” _Ann. Surg._, - 1918, lxvii. 1. - - 241. ROBERTSON, O. H.: “The effects of experimental plethora on - blood production.” _Journ. Exper. Med._, 1917, xxvi. 221. - - 242. ROBERTSON, O. H.: “A method of citrated blood transfusion.” - _Brit. Med. Journ._, 1918, i. 477. - - 243. ROBERTSON, O. H.: “Transfusion with preserved red cells.” - _Brit. Med. Journ._, 1918, i. 691. - - 244. ROBERTSON, O. H.: “Memorandum on blood transfusion.” _Rep. of - the Med. Res. Com._, iv. 1919, 143. - - 245. ROBERTSON, O. H., & BOCK, A. V.: “Memorandum on blood volume - after hæmorrhage.” _Rep. of the Med. Res. Com._, vi. 1919, 213. - - 246. ROBERTSON, O. H., & BOCK, A. V.: “Blood volume in wounded - soldiers.” _Journ. Exp. Med._, 1919, xxix. 139. - - 247. ROSE, A.: “A case of melæna neonatorum successfully treated by - the injection of blood serum.” _Brit. Med. Journ._, 1917, ii. 762. - - 248. ROSE, C. W., & HUND, E. J.: “Treatment of pneumonic - disturbances complicating influenza.” _Journ. Am. Med. Assoc._, - 1919, lxxii. 642. - - 249. ROUS, P., & TURNER, J. R.: “The preservation of living - red blood cells in vitro. I. Methods of preservation. II. The - transfusion of kept cells.” _Journ. Exp. Med._, 1916, xxiii. 219. - - 250. ROUS, P., & WILSON, G. W.: “Fluid substitutes for transfusion - after hæmorrhage.” _Journ. Am. Med. Assoc._, lxx. 219-222. - - 251. RUECK, G. A.: “Transfusion by the gravitation method.” _Med. - Rec._, 1915, lxxxvii. 354. - - 252. SALANT, W., & WISE, L. E.: “The action of sodium citrate and - its decomposition in the body.” _Journ. Biolog. Chem._, 1917, - xxviii. 27. - - 253. SANFORD, A. H.: “Iso-agglutination groups: a diagram showing - their interrelation.” _Journ. Am. Med. Assoc._, 1916, lxvii. 808. - - 254. SANFORD, A. H.: “Selection of the donor for transfusion.” - _Journ. Lancet_, 1917, xxxvii. 698. - - 255. SANFORD, A. H.: “A modification of the Moss method of - determining iso-hæmagglutination groups.” _Journ. Am. Med. Assoc._, - 1918, lxx. 1221. (Also in _Collected Papers of the Mayo Clinic_, - 1918, x. 504.) - - 256. SATTERLEE, H. S., & HOOKER, R. S.: “Experiments to develop a - more widely useful method of blood transfusion.” _Arch. Int. Med._, - 1914, xiii. 51. - - 257. SATTERLEE, H. S., & HOOKER, R. S.: “The further development - of an apparatus for the transfusion of blood.” _Surg. Gynec. and - Obst._, 1914, xix. 235. - - 258. SATTERLEE, H. S., & HOOKER, R. S.: “The use of hirudin in the - transfusion of blood.” _Journ. Am. Med. Assoc._, 1914, lxii. 1781. - - 259. SATTERLEE, H. S., & HOOKER, R. S.: “Transfusion of blood, with - special reference to the use of anticoagulants.” _Journ. Am. Med. - Assoc._, 1916, lxvi. 618. - - 260. SAUERBRUCH: “Artery of donor introduced directly into - recipient’s vein for transfusion of blood.” _Münch. Medizin. - Wchnschr._, 1915, lxii. No. 45. - - 261. SCHEEL, O., & BANG, O.: “Transfusion in a case of pernicious - anæmia.” _Norsk Mag. f. Lægevidenskaben_, 1920, March. - - 262. SCHLOSS, C. M., & COMMINSKEY, L. J. J.: “Spontaneous - hæmorrhage in the new-born.” _Am. Journ. Dis. 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Rec._, 1912, lxxxi. 835. - - 270. SPENCER, W. G.: “Transfusion of blood in civil practice.” - _Med. Sci. Abstr. and Rev._, 1919, i. 309. - - 271. STANLEY, L. L.: “Blood transfusion apparatus.” _Journ. Am. - Med. Assoc._, 1920, lxxiv. 671. - - 272. STANSFELD, A. E.: “The principles of the transfusion of - blood.” _Lancet_, 1917, i. 488. - - 273. STANSFELD, A. E.: “An apparatus for the transfusion of blood - by the citrate method.” _Lancet_, 1918, i. 334. - - 274. SYDENSTRICKER, V. P. W., MASON, V. R., & RIVERS, T. M.: - “Transfusion of blood by the citrate method.” _Journ. Am. Med. - Assoc._, 1917, lxviii. 1677. - - 275. TARR, E. M.: “Intravenous injections in infancy. Advantage of - the superior longitudinal sinus route.” _Arch. Pediatr._, 1919, - xxxvi. 71. - - 276. TELFER, S. V.: “Note on the preparation of sterile gum acacia - solution for intravenous injection.” _Rep. of the Med. Res. Com._, - i., 1919, 42. - - 277. TERRIEN, E.: “Transfusion of blood in malignant measles.” - _Bull. Soc. Méd. des Hôp._, 1919, xliii. 1134. - - 278. THALIMER, W.: “Hæmoglobinuria after a second transfusion with - the same donor.” _Journ. Am. Med. Assoc._, 1921, lxxvi. 1345. - - 279. THOMAS, T. G.: “The intravenous injection of milk as a - substitute for the transfusion of blood.” _N.Y. Med. Journ._, 1878, - xxvii. 449. - - 280. UNGER, L.: “Melæna neonatorum.” _Wien. Klin. Woch._, 1912, - xxxix. - - 281. UNGER, L. J.: “A new method of syringe transfusion.” _Journ. - Am. Med. Assoc._, 1915, lxiv. 582. - - 282. UNGER, L. J.: “Recent simplifications of the syringe method - of transfusion.” _Journ. Am. Med. Assoc._, 1915, lxv. 1029. - - 283. UNGER, L. J.: “Transfusion of unmodified blood, an analysis of - one hundred and sixty-five cases.” _Journ. Am. Med. Assoc._, 1917, - lxix. 2159. - - 284. UNGER, L. J.: “Precautions necessary in the selection of a - donor for blood transfusion.” _Journ. Am. Med. Assoc._, 1921, - lxxvi. 9. - - 285. VINCENT, B.: “Blood transfusion for hæmorrhagic diseases of - the new-born. The use of the external jugular vein in infants.” - _Boston Med. and Surg. Journ._, 1912, clxvi. 627. - - 286. VINCENT, B.: “Blood transfusion with paraffin-coated needles - and tubes.” _Surg. Gynec. and Obstet._, Nov. 1916. - - 287. VINES, H. W. C.: “Anaphylaxis in the treatment of hæmophilia.” - _Quart. Journ. Med._, 1920, xiii. 257. - - 288. VINES, H. W. C.: “The coagulation of the blood. I. The rôle of - calcium. II. The clotting complex.” _Journ. Phys._, 1921, lv. 86, - 287. - - 289. VOGEL, K. M., & McCURDY, U. F.: “Blood transfusion and - regeneration in pernicious anæmia.” _Arch. Internal. Med._, 1913, - xii. 707. - - 290. WAAG, A.: “Repeated small injections of blood in pernicious - anæmia.” _Münch. Medizin. Wchnschr._, 1921, lxviii. 677. - - 291. WALLICH, V., & LEVADITI, C.: “Recherches sur les réactions - sanguines, à considérer à propos de la transfusion de sang.” _Bull. - de l’Acad. de Méd._, 1914, lxxviii. No. 17. - - 292. WARD, G.: “Transfusion of plasma.” _Brit. Med. Journ._, 1918, - i. 301. - - 293. WATSON, J. J.: “A method of fixation of vein to facilitate the - introduction of a needle for intravenous injections.” _Journ. Am. - Med. Assoc._, 1911, lvii. 383. - - 294. WAUGH, W. G.: “An investigation of the end result in one - hundred and twenty-four cases of blood transfusion.” _Brit. Med. - Journ._, 1919, ii. 39. - - 295. WEIL, P. E.: “Serum treatment of hæmophilia.” _Lancet_, 1920, - ii. 300. - - 296. WEIL, R. J.: “Sodium citrate in the transfusion of blood.” - _Journ. Am. Med. Assoc._, 1915, lxiv. 425. - - 297. WILLIAMSON, H.: “Blood transfusion before operation in severe - secondary anæmias.” _Lancet_, 1920, i. 867. - - 298. WOLTMANN, H.: “Transfusion by the citrate method in a - sixty-hour-old baby with melæna neonatorum.” _Am. Journ. Med. - Sci._, 1915, lxv. 2163. - - 299. WREN, SIR C.: “An account of the rise and attempts of a - way to conveigh liquors immediately into the mass of blood.” - _Philosophical Trans._, 1665, i. 128. - - 300. ZIEMSSEN, VON: “Ueber die subcutane Blutinjection und über - eine einfache Methode der intravenösen Transfusion.” _Münch. Med. - Wchnschr._, 1892, xix. 323. - - 301. ZIMMERMANN, R.: “Blood transfusion in gynæcological cases.” - _Münch. Med. Wchnschr._, 1920, lxvii. 898. - - 302. ZIMMERMANN, R.: “Testing donor’s blood before transfusion.” - _Zentralbl. f. Chir., Leipzig_, 1920, xliv. 1146. - - - - -INDEX - - - Abdominal operations, shock in relation to, 27 - value of transfusion following, 32 - - Abdominal veins, “bleeding into,” 27 - - Accidents, loss of blood following, 20 - - Acholuric jaundice, blood condition in, 93 - blood groups of patients with, 93 - transfusion in, 94 - - Acidosis, in pregnancy, 63 - - Agglutination, 84, 85 - abnormal, 56 - among animals, 79 - in infants and children, 84 - method of the test, 101 - phenomenon of, 71-73 - potential, of fœtal corpuscles, 85 - preceding hæmolysis, 70, 76 - - Agglutinins, 71 - in the blood, discovery of, 15 - in maternal blood serum and milk, 86 - “major” and “minor,” 73 - “minor” in citrated blood, 123 - - “Agglutinophilic” properties of blood corpuscles, 72, 85 - - Agote, Prof., first transfusion of citrated blood by, 16 - - Air hunger, 21 - - Air-lock in transfusion apparatus, 125, 131, 133 - - Alkaline solution in treatment of shock, 34 - - Alkalinized blood, 63 - - Amaurosis, 21 - - Amputations, value of transfusion following, 32 - - Anæmia, 19, 50 - acute, 19, 20 - amount of blood necessary in transfusion treatment, 25 - effect of transfusion on, 22 - following hæmorrhage, 20, 24 - signs and symptoms of, 20 - transfusion treatment of, 31 - aplastic, 50 - hæmophilia with, 48 - splenic, 50 - _see also_ Pernicious anæmia - - Anæsthesia, transfusion in conjunction with, 33 - - Anæsthetics, shock accentuated by administration of, 31 - - Anaphylactic shock, following transfusion, 77 - in pernicious anæmia, 57 - influence on coagulation time of blood, 45 - - Anastomosis, Crile’s method, 109 - for direct transfusion, 108, 109 - - Antecubital veins, injection of blood into, 134, 135 - - Anti-agglutinins, 74 - - Antibodies, in the blood, 58 - - Anticoagulants, 16 - action of, 120, 122 - in hæmophilia, 47 - sodium citrate, 121 - transfusion with, 118 - - Aplastic anæmia, 50 - - Arm tourniquet, 126, 128 - - Army, blood transfusion in, 17 - - Arteries, in direct transfusion, 108, 109 - occlusion of, prevention of, 109 - selection of, for transfusion, 108 - - Asthma, transmission of, 68 - - Auto-hæmolysins, development of, 94 - - Auto-hæmolysis of blood outside the body, 94 - phenomenon of, 94, 95 - - - Bacteria, blood inhibiting growth of, 58 - - Bacterial infections, 58-63 - transfusion in relation to, 58, 60 - - Benzol poisoning, transfusion treatment of, 65, 66 - - Blood, administration of, apparatus for, 115, 126, 127, 130-133 - methods, 108, 112, 130-135 - time occupied in, 131, 132 - agglutinins and iso-agglutinins in, 15, 71, 72, 74 - amount in the body, how measured, 22, 23 - animals’, use of, 5, 6, 8, 9, 15 - anti-agglutinins in, 74 - antibodies in, 58 - auto-hæmolysis of, 94 - bactericidal power of, 58 - calcium content of, 120 - citrated, _see_ Citrated blood - clotting of, _see_ Coagulation - coagulation of, _see_ Coagulation - defibrinated, early use of, 11, 12 - examination of, for transfusion, 56, 57, 95 - hydrogen-ion concentration of, 28 - immunized, in pyogenic infections, 58 - inhibiting growth of bacteria, 58 - loss of, _see_ Hæmorrhage - maternal, agglutinins in, 86 - of donors, _see_ Blood donors - of patients, reinfusion with, 42, 43 - testing of, 56 - rapid administration, danger of, 78 - substitutes for, 35, 36 - testing of, for transfusion, 68, 83, 92, 95 - total quantity in the body, 22 - transfused, corpuscles in, 37 - relative value of corpuscles and plasma in, 36, 37 - withdrawal of, methods and technique, 108, 112, 116, 126-128 - - Blood clot, mechanism of formation of, 119 - rapid hæmorrhage causing, 24 - _see also_ Coagulation - - Blood corpuscles, “agglutinophilic” properties of, 72, 85 - and plasma, relative value of, 36, 37 - clumping together of, 70 - condition during shock, 39 - conditions due to alterations in, 50 - destruction of, in the toxæmias, 64 - effect of transfusion on, 52 - fœtal, potential agglutination of, 85 - in transfused blood, 36, 37 - function of, 37 - quantity and concentration during shock, 28 - transfusion of, 64 - - Blood count, during shock, 39 - following hæmorrhage, 39 - following transfusion, 40 - in pernicious anæmia, 51, 53-56 - - Blood diseases, 50-58 - - Blood donor, 69 - blood of, 56, 57 - agglutinating power of serum of, 72-74 - testing of, 68 - transmission of disease by, 67, 68 - characteristics of, 100 - choice of, 68, 96-107 - effect of blood loss on, 99 - for new-born infants, 49 - for pernicious anæmia, 56, 57 - injury to, during transfusion, 111, 124 - members of patient’s family as, 85, 90, 92, 95 - “professional,” 69, 98 - testing of, 83, 92, 95-97 - for blood groups, 101 - treatment of, 60, 99, 100 - “universal,” 72, 73 - vaccine treatment of, prior to withdrawal of blood, 60 - withdrawal of blood from, 108, 109, 124 - by anastomosis, 108, 109 - by Kimpton-Brown tube, 116, 117 - by needle, 126-128 - by syringe, 112, 113 - - Blood groups, 67, 69, 70, 101 - among animals, 79 - and disease, relation between, 81, 93 - classification of, 70, 71 - compatibility of, 72, 75, 80 - in families, 84, 90, 92 - testing of, 102 - earliest classification of, 15 - family incidence of, 84, 90, 92 - incidence among our own population, 83 - incompatibility of, 80, 92 - earliest reference to, 6 - in animals, 80 - in families, 84, 90, 92 - symptoms of, 75-77 - testing for, 101, 102 - inheritance of, 86, 87, 90, 91 - medico-legal considerations, 92 - maternal, compared with those of infants, 86, 92 - over-lapping of, 72, 96 - pathology of, 79 - phenomena of, 69-75 - physiology of, 79 - popular beliefs concerning, 84 - racial incidence of, 81, 82 - reactions between the serum and corpuscles of, 70, 71, 72, 73 - testing for, in blood donors, 97, 101 - transfusion in relation to, 95 - “unit characters” in, 86, 87, 88 - - Blood measurements, 22, 23 - - Blood plasma, in transfused blood, 36, 37 - - Blood pressure, 21 - as an indication for transfusion, 40 - danger points in, 21 - following loss of blood, 21 - low, essential feature of shock, 27 - transfusion treatment of, 32 - - Blood reactions, 70, 71, 72, 80, 101 - clinical picture of, 75 - disease in relation to, 93 - family incidence of, 84, 90, 92, 95 - following transfusion, 95, 96, 122, 123 - in infants, 84, 90, 92 - incompatibility of, transfusion in relation to, 96 - intensity of, variations in, 73 - recognition of symptoms of, 75-77 - variation in degree of, 76 - - Blood recipients, “universal,” 72, 95 - - “Blood relations,” transfusion in relation to, 84, 92, 95 - - Blood serum, agglutination test of, 101 - preservation of, 101, 102 - stock, 101 - collection of, 102 - - Blood volume, changes in, in hæmorrhage and shock, 24, 25, 27 - diminution in shock, 27, 32 - estimation of, 22 - imperfect oxygenation due to, 36 - life dependent on, 24, 25 - - Blundell, James, his “impellor,” 10, 11 - transfusion by (in 1818), 10, 11 - - Body, total quantity of blood in the, 22 - - Breathing, difficult, during transfusion, 78 - - Burns, transfusion for shock due to, 136 - - - Calcium, action of, 120 - in the blood, forms in which present, 120 - precipitation of, 119 - - Cancer, transfusion for, 9, 18 - - Cannula, for direct transfusion, 110 - for indirect transfusion, 130 - - Capillary circulation, condition during shock, 39 - stagnation of, following hæmorrhage and shock, 27, 29 - - Carbon monoxide poisoning, 64 - condition of the blood in, 64 - transfusion treatment of, 64, 65 - - Children, transfusion of, technique, 134 - _see also_ Infants - - Chloroform, shock accentuated by administration of, 31 - - Chlorosis, 50 - - Circulation, blood volume necessary to maintain balance of, 24, 25 - capillary and venous, comparison during shock, 39 - condition during shock and hæmorrhage, 27, 28, 29, 39 - stagnation of, 28 - _see also_ Blood - - Citrate reactions, 122, 123 - - Citrated blood, 16, 121, 124 - administration of, methods, 129-134 - keeping and care of, 128, 129 - reaction following use of, 122, 123 - transfusion of, 121, 124 - first recorded case of, 16 - in pernicious anæmia, 51, 56 - _see also_ Sodium citrate - - Clotting, _see_ Coagulation - - Coagulation, deficient, following hæmorrhage, 41 - difficulties connected with, in early experiments, 11, 12 - effect of transfusion on, 42 - - Coagulation, mechanism of production of, 119 - outside the body, 118, 119 - prevention of, 114, 120 - - Clotting, prevention of, by sodium citrate, 119, 120 - prevention of, during transfusion, 109, 110, 112 - transfusion simplified by prevention of, 119 - - Coagulation time, anaphylactic shock influencing, 45 - effect of transfusion on, 46, 47 - hæmorrhage in relation to, 44, 45 - in jaundice, 44 - prolongation of, 44 - - Coal-gas poisoning, transfusion treatment of, 64 - - Coga, Arthur, 8 - - Cold, predisposing to shock, 29, 30 - - Cox, Thomas, transfusion experiments by, 3 - - Crile, improvement in technique of transfusion by, 15 - method of direct transfusion, 109 - - Curtis and David, improvements in technique of transfusion by, 16 - - - Daniel, of Leipsic, 3 - - Darwin, Erasmus, 9 - - Death, loss of blood causing, 24 - - Denys, John, first human transfusion performed by, 3, 5, 6 - - Diabetes mellitus, transfusion in, 66 - - Diphtheria, 60 - acute toxæmia in, 60 - experimental transfusion in, 60, 61 - - Direct transfusion, apparatus for, 109, 110 - methods, 108, 109, 110 - objections to, 110, 111 - technique of, 108-111 - - Disease, relation between blood groups and, 81, 93 - transmission by blood transfusion, 68 - - Drysdale, Dr. J. H., 52 - - Duodenal ulcer, severe hæmorrhage from, transfusion treatment, 41 - - - Eclampsia, “fœtal threat” in relation to, 85 - transfusion treatment, 62 - - Ectopic gestation, rupture of, transfusion following, 42 - - Elsberg and Bernheim’s method of direct transfusion, 109 - - Emboli, multiple, 77 - - Endocarditis, transfusion for, 60 - - Ether, shock accentuated by administration of, 31 - - - Fever, transfusion for, 9 - - Fluids, administration of, during shock, 34 - - “Fœtal threat,” 85 - - Folli, Francesco, supposed blood transfusion by (1654), 2 - - Fontanelle, use of, 135, 136 - - Forced fluids, 34 - - Fullerton’s method of direct transfusion, 110 - - - Gametes, segregation of, 88 - - Gastric ulcer, severe hæmorrhage from, transfusion treatment, 41 - - Grafts, tissue, 80 - - Gum transfusion, 35, 36, 37 - and blood transfusion, relative value of, 35, 37 - objections to, 36 - - Gurye, Gaspar de, 6 - - - Hæmatemesis, treatment of, 41 - - Hæmoglobin percentage, during shock and hæmorrhage, 39 - - Hæmoglobinuria, 6, 7, 70 - as symptom of blood reaction, 76 - following blood transfusion, 76 - paroxysmal, blood condition in, 94 - - Hæmolysed blood, toxicity of, 77 - - Hæmolysins, 71 - - Hæmolysis, 94, 95 - agglutination preceding, 70, 76 - early reference to, 6 - - Hæmophilia, anæmia with, 48 - anticoagulants in, 47 - blood condition in, 45 - sodium citrate administration in, 47, 48 - transfusion treatment of, 45-48 - - Hæmophilics, coagulation time of blood of, 46, 47 - transfusion beneficial to, 46 - - Hæmorrhage, 20 - acute anæmia following, 20, 24 - blood counts following, 39 - blood-volume changes in, 24, 25, 27 - - Hæmorrhage, coagulation time in relation to, 44, 45 - condition of blood following, 24, 27, 28, 39 - danger of, 20, 23 - effects of, how combated, 33 - following gastric or duodenal ulcer, transfusion treatment, 41 - general treatment of, 31, 33 - gum treatment of, 35, 36 - in new-born infants, transfusion treatment, 49 - intraperitoneal, 42 - limits of, 24 - post-partum, transfusion treatment, 42 - rapid, 23, 24 - reflex compensation for, 99 - reinfusion treatment of, 42 - saline treatment of, 33 - secondary, 40, 41 - indications for transfusion in, 41 - shock always associated with, 20, 26 - shock and, clinical difference between, 38 - signs and symptoms of, 38 - transfusion treatment of, 20, 25, 31 - effects of, how judged, 40 - indications for, 40 - traumatic, 40 - - Hæmorrhagic diseases, 44-50 - - Hæmostasis, blood transfusion producing, 42, 44, 45, 48 - - Harvey, William, his theory of the circulation, 2 - - Heart, dilatation of, 78 - effect of loss of blood on, 23 - - Helmholtz, method of transfusion of infants, 135 - - Heredity, blood groups in relation to, 86, 87, 90, 91 - Mendelian theory of, 86, 90 - - Higginson’s transfusion instrument, 13, 14 - - Hirudin, use of, 16 - - Histamine, 30 - production of, 30 - production of shock by, 30 - - Horse asthma, transmission of, 68 - - Howard’s method of transfusion of infants, 135 - - Hydrogen-ion concentration in the blood, 28, 31 - shock in relation to, 28, 32 - - Hydrophobia, transfusion for, 9 - - - Immunized blood, transfusion by, in pyogenic infections, 58 - - Incompatibility, symptoms of, 6, 75 - - Indirect transfusion, 111 - - Infants, blood groups in, 84, 92 - compared with those of mothers, 86, 92 - blood reactions in, 84, 90, 92 - transfusion of, 48 - conditions necessitating, 49, 134 - dosage, 136 - technique, 134-136 - with maternal blood, 85, 92 - withdrawal of blood from, 136 - - Influenzal pneumonia, transfusion for, 61 - - Innocent VIII, 2 - - Internal saphenous vein, injection of blood into, in infants, 135 - - Iso-agglutinins, 72, 79 - distribution among animals, 79, 80 - - Iso-hæmolysins, 72, 79 - in animals, artificial reproduction of, 96 - - Isotonic saline solution in treatment of shock, 34 - - - Jaundice, 44 - acholuric, transfusion in, 94 - blood groups in patients with, 93 - hæmorrhage following operation in cases of, 44 - transfusion in cases of, 44 - - Joekes, Dr., 52, 57 - - Jugular vein, injection of blood into, 135 - - - Keith, on blood volume changes, 24, 27 - on shock and hæmorrhage, 32 - - Kimpton and Brown, improvements in technique of transfusion by, 16 - - Kimpton-Brown tube, whole blood transfusion with, technique, 114 - - King, Edmund, transfusion experiments by, 3, 4, 8 - - - Lamb’s blood, early transfusions with, 5, 9, 15 - - Legitimacy, inheritance of blood groups in relation to, 92 - - Leukæmia, 50 - blood groups in patients suffering from, 81 - - Lewisohn’s sodium citrate experiments, 16, 120, 122, 123 - - Longitudinal sinus, use of, 135 - - Lower, Richard, transfusion experiments by, 3, 8 - - - Malaria, transmission by transfusion, 67, 68 - - Malignant disease, blood groups in patients suffering from, 81, 93 - - “Maternal threat,” 85, 92 - - Measles, blood injections in, 62 - - Median basilic vein, accessible for direct transfusion, 108 - incision of, 130 - puncture of, 126-128 - - Melæna neonatorum, transfusion for, technique, 134, 135 - value of transfusion in, 48 - - Mendelian theory, 86, 90 - of blood groups, 86, 87, 88, 90 - - Milk, injection of, 15 - maternal, agglutinins in, 86 - - Muscle, damaged, production of histamine from, 30 - - - Needle, for transfusion, 126 - case of, 126 - improved form of, 113 - - Nephritis, transfusion treatment of, 63 - - New-born infants, blood donors for, 49 - blood reactions of, 84, 90, 92 - hæmorrhagic disease of, 48, 49 - transfusion of, 48 - technique, 134-136 - with maternal blood, 84, 85, 92 - - Nitrobenzol poisoning, transfusion treatment of, 65 - - - Obstetrics, transfusion in, 42 - - Operations, shock following, 31 - value of transfusion following, 32 - - Osmotic pressure, 36 - significance of, 36 - - Oxygenation, imperfect, blood loss causing, 36 - solutions increasing, 37 - - Oxyhæmoglobin, conversion into carboxyhæmoglobin in carbon monoxide - poisoning, 64 - - Pain, predisposing to shock, 29 - - Paraffin wax, coating of glass tube with, 114, 116 - in prevention of clotting, 110, 114 - - Paroxysmal hæmoglobinuria, blood conditions in, 94 - - Pedigree of blood groups, 90 - - Pellagra, transfusion in cases of, 66 - - Pepys, Samuel, 7, 8, 9 - - Pernicious anæmia, 50 - blood condition in, 93 - blood count in, 51, 53-56 - blood groups in patients with, 93 - subcutaneous blood injections in, 58 - transfusion treatment of, 50-58, 95 - complications of, 57 - cases illustrating, 53-55 - choice of blood donor, 56, 57 - dosage, 52 - reactions following, 57 - - Perspiration, blood loss due to, 28 - - Placenta prævia, transfusion following, 42 - - Pneumonia, transfusion in cases of, 61 - - Poisoning, transfusion treatment of, 64, 65 - - Post-operative shock, 31 - - Post-partum hæmorrhage, 42 - - Pregnancy, toxæmias, of “fœtal threat” in relation to, 85 - transfusion treatment of, 62 - - “Professional” blood donor, 69, 98 - - Purpura, transfusion in cases of, 49, 50 - - Pyæmia, transfusion in cases of, 59 - transfusion in, 58 - - - Radial artery, accessible for direct transfusion, 109 - exposure of, 111 - objections to use of, 111 - - Reactions, 75, 76 - following transfusions, 57, 122, 123 - _see also_ Blood reactions - - Reinfusion with patient’s own blood, 42, 43 - - Rejuvenation, 136 - - Replacement of blood, complete, 136 - - Respiratory system, effect of loss of blood on, 23 - exhaustion of, 21 - - Robertson, Bruce, transfusion of infants and children by, 135, 136 - - Robertson, Oswald, transfusion with citrated blood by, 121, 124 - - “Robertson’s bottle,” 124, 125 - - - Saline infusion, treatment of shock by, 33 - - Saphenous vein, internal use of, 130, 135 - - Sauerbruch’s method of direct transfusion, 108 - - Segregation of the gametes, 88 - - Septicæmia, transfusion for, 59, 136 - - Serum, _see_ Blood serum - - Shock, 20 - abdominal operations in relation to, 27 - alkaline administration during, 34 - anaphylactic, _see_ Anaphylactic shock - avoidance of, following hæmorrhage, 29 - blood count during, 39 - blood volume changes in, 24, 25, 27, 32 - capillary system during, 27, 28, 29 - causal theories of, 26, 27 - conditions of the blood during, 24, 27, 28, 39 - effects of, how combated, 33 - experimental production of, 30 - fluid administration during, 34 - gum treatment of, 35, 36 - hæmorrhage always associated with, 26 - hæmorrhage and, differential diagnosis, 38, 39 - hydrogen-ion concentration in relation to, 28, 32 - low blood pressure the essential feature of, 27 - mechanism of production of, 30 - post-operative, 31 - primary, 29 - reinfusion treatment, 42 - saline treatment of, 33 - secondary, 29 - conditions predisposing to, 29 - signs and symptoms of, 26, 29, 38 - theories regarding, 26 - toxic theory of, 30 - transfusion treatment of, 20, 26, 31 - indications for, 40 - - Skin eruption, as symptoms of blood reaction, 76, 77 - - Sodium bicarbonate, in treatment of shock, 34 - - Sodium citrate, absorption and elimination of, 120 - action of, 122 - as an anticoagulant, 16, 121 - coagulation time of the blood reduced by, 47 - dosage, 121, 122 - elimination of, 120 - form in which used, 123 - in hæmophilia, 47 - in prevention of clotting, 119, 120 - reactions following use of, 122, 123 - tolerance to, 122 - toxicity of, 77 - - Sodium phosphate, use of, 16 - - Solutions, for transfusion, essential constituents of, 36, 37 - viscosity and osmotic pressure of, 36 - - Spinal anæsthesia, transfusion in conjunction with, 33 - - Splenic anæmia, 50 - - Stansfeld’s apparatus, 134 - - Staphylococcal septicæmia, blood transfusion in, 59, 60 - - Sterility and blood groups, 80 - - Streptococcal septicæmia, blood transfusion in, 136 - - Syphilis, transmission by blood transfusion, 68 - - Syringe, cleansing of, 114 - Higginson’s, 13, 14 - whole blood transfusion with, technique, 112-114 - - - Tissue transplantation, success of, dependent upon compatibility of - blood groups, 80 - - Tissues, damage to, producing toxic substances, 30 - - Tourniquet, Canti’s, 126, 128 - - Toxæmia, 58-66 - acute, in bacterial diseases, 60 - blood transfusion in, 31, 58, 60, 61 - of pregnancy, transfusion treatment of, 62 - traumatic, 30-32 - production of, 30 - - Toxic theory of shock, 30 - - Transfusion, apparatus for, 115, 126, 127, 130-133 - in early experiments, 10, 13 - recent improvements in, 15 - continuous, 60 - direct method, technique, 108-111 - early objections to, 9 - history of, 1 - ideal method of, 124, 132 - indirect method, technique, 111-112 - of infants, 134 - technique, 134 - recent advances in knowledge and technique of, 15-17 - repeated, 57 - Robertson’s citrate method, 121, 124 - apparatus for, 124, 134 - whole blood, with syringes, technique, 112 - with anticoagulants, technique, 118-134 - with Kimpton-Brown tube, 114 - - Traumatic toxæmia, 30-32 - - Tuberculosis, transfusion in, 62 - - Twins, blood groups in, 92 - - Typhoid, transfusion in, 62 - - - “Universal donors,” 72, 73 - - “Universal recipients,” 72 - - Urine, hæmoglobin in, 39, 70, 76 - suppression of, 76, 77 - - Urticaria, following transfusion, 77 - - Uterus, rupture of, 42 - - - Vaccine, injection of, into blood donors, 59, 60 - - Vaso-motor failure, in shock, 26 - - Vein, for direct transfusion, 108, 109 - injection of blood into, 134, 135 - insertion of cannula in, 131 - occlusion of, prevention of, 109 - puncture of, 113 - technique, 126-128 - prevention of injury to, 113, 124 - - Venesection, preceding transfusion, 60 - in carbon monoxide poisoning, 65 - - Venospasm, 27 - - Venous circulation, condition during shock, 39 - - Viscosity, 36 - significance of, 36 - - Vital red, use of, 23 - - - War, transfusion in, 17 - - Water, during severe shock, 34 - - Whole blood transfusion, apparatus for, 114 - objections to, 118 - prevention of clotting, 114, 118 - with Kimpton-Brown tube, technique, 114-118 - with syringes, 112-114 - - Willis, Thomas, 3 - - “Wound shock,” 29 - - Wren, Sir Christopher, vein injections by, 2, 3 - - -FOOTNOTES: - -[1] The first reference to this that I can find is in “Moines et -Papes,” by Emile Gebhardt, _La Chronique Médicale_, November 1912. - -[2] _Life and Times of Rodrigo Borgia_, A. H. Mathew, D.D., 1912, -p. 66. - -[3] This refers to the experiment of Denys, mentioned above. - -[4] Birch’s _History of the Royal Society_, 1756, ii. p. 216. - -[5] The notation used here is that initiated by Moss in 1910. This -does not agree with the notation introduced three years previously by -Jansky, the Groups I and II of Moss corresponding to the Groups IV -and III of Jansky and _vice versa_. The difference has given rise to -confusion and some disasters, and it has been recently recommended -by an American Medical Committee that the notation of Jansky be -universally adopted on grounds of priority. This decision is no -doubt fully justified in American practice, but in this country the -notation of Moss has been so generally used that I have not attempted -to reverse it. The possible dangers that may arise should, however, -be realized. - -[6] _Mendelism_, R. C. Punnett, 5th ed., Macmillan, 1919. - -[7] J. A. Kolmer, _Infection, Immunity, and Specific Therapy_, ed. -2, Saunders Co., 1917, p. 287: “With the increasing number of blood -transfusions the phenomena of iso-agglutination and iso-hæmolysis -are of considerable practical importance, especially if the patient -is suffering from cancer, when the serum is likely to be actively -hæmolytic for the donor’s corpuscles.” No authority is given. - -[8] This embodies the same principle as the “dropper” designed by R. -D. Laurie. - -[9] A very convenient form of tourniquet is that designed by R. G. -Canti. It is sold by Messrs. Maw & Sons, and by Messrs. 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