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.
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.
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.
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.