The Frequency and Mechanism of Haemolysis in the Leukaemias, Reticuloses and Myeloproliferative Diseases

MANY patients with frank haemolysis in association with leukaemias, reticuloses and myeloproliferative diseases have now been described and the subject has been rcviewed by Dacie (1954, Chapter 13). It has become apparent, however, that cryptic haemolysis may be prcscnt without obvious signs or even significant anaemia, especially by the use of erythrocyte survival tests. Early survival tests were done by the Ashby (1919) nicthod which has the great disadvantage that the survival of a donor’s and not the patient’s erythocytes, is measured. Such survival studies were made by Brown (~gjo) , Stats (1950), Berlin (1951), Brown, Elliott and Young (1951), Ross, Crockett and Emerson (1951), Bottner and Schlegel(1952), Aas (1952)~ Hyman (1g54), Ross, Crockett, Finch and Emerson (1954), Boiron, Paoletti, Tubiana, Schapira, Dausset and Bernard (1955)~ Hyman, Harvey and Gellhorn (1955), Wassernian, Stats, Schwartz and Fudenberg (1955), and Hyman, Gellhorn and Harvey (1956). These tests showcd the presence of abnormal haemolysis in over 90 per cent of the patients. Radioactive methods have made it possible to estimate the approximatc lifc-span of the patient’s own erythrocytes. Lawrence, Berlin and Huff (1953), Berlin, Lawrence and Lee (1954) and Boiron and co-workers (1955) used 14C-labelled glycine and studied 16 patients. Thc radioactive chromium (51Cr) method introduced by Gray and Sterling (1950) has becn used in patients with these diseases by Weinstein and LeRoy (1953), Read, Wilson and Gardncr (1954), Jensen (1957), Schloesser, Korst, Clatanoff and Schilling (1957), Frcymann, Burrell and Marler (1958), Fudenberg, Barry and Dameshek (1958), Wctherlcy-Mein, Epstein, Foster and Grimes (1958) and Freyniann, Vander, Marler and Meyer (1960). These authors studied 65 patients. Assuming as ‘normal’ results an erythrocytc life-span of more than 100 days, a ‘half chromium time’ of over 20 days, and a loss of 51Cr from the labclled erythrocytes of less than 4 per cent per day, then abnormal haemolysis was shown in 58.5 per cent of the patients. The 14C-labelled glycinc and 51Cr methods togethcr showcd a haemolytic state in 62 per cent of the patients, which is much less than had bccn shown by the Ashby method. The present investigation was undertaken to determine the incidencc of a haemolytic process in patients with leukaemias, various reticuloses and myeloyroliferative diseases using for the determination of erythrocyte survival the radiochromium method of Mollison and Veal1 (1955) for which the rate of loss of 51Cr from the tagged erythrocytes has been cstablished within narrow limits. The survival of group-0, Rh-ncgative (cde) erythrocytes was tcsted in some patients after their own erythrocytes had survived normally, to discover whcther or not the Ashby method would have indicated the fite of the recipient’s own erythrocytes. Tests of erythrocyte fragility and for antibodies, reticulocyte counts and blood-film inspection were done on all patients to determine as far as possible the mechanisms underlying symptomatic haeinolytic states. Occult blood tests on the stools were done during the coursc of the erythrocyte survival tests to eliminate false results due to gastro-intestinal blood loss.