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.