The immune haemolytic anaemias: a century of exciting progress in understanding

The growth in knowledge of the scientific basis of disease and consequent advances in the practice of medicine that have taken place in the past century have been truly remarkable. This is certainly true of the haemolytic anaemias, which have been a main interest of the author since the mid-1930s. At that time, the cause and mechanism of important disorders such as the acquired antibodydetermined (immune) haemolytic anaemias, haemolytic disease of the newborn, hereditary spherocytosis and paroxysmal nocturnal haemoglobinuria were unknown or but partially understood. The purpose of this short review is to record and highlight some of the most significant advances in knowledge of the acquired immune haemolytic anaemias that have been made between the first decade and the end of the twentieth century. First, however, a diversion. According to Crosby (1952), William Hunter of London, in an article on pernicious anaemia published in 1888, was the first to use the term `haemolytic' to denote an anaemia caused by excessive blood destruction. By the turn of the century, the term was being widely used in clinical literature, e.g. by Widal et al (1908a,b) and Micheli (1911), and in experimental studies, e.g. by CantacuzeÁne (1900). At that time, however, and for a decade or so later, no reliable data were available as to the life-span of the erythrocyte in health. Peyton Rous, in his comprehensive review `Destruction of the red blood corpuscles in health and disease' (Rous, 1923), concluded that the generally held view in the early 1930s was that about one-fifteenth of the erythrocyte mass was destroyed daily. Rous was aware of the pioneer work of Winifred Ashby (1919a,b), who, by following the survival of serologically distinct but compatible transfused erythrocytes, had found that normal erythrocytes might live for up to 100 d in the recipients' circulation. The difficulty in accepting Ashby's conclusions without question was that she was unable, using her technique, to measure the life-span of the experimental subjects' cells in their own environment. Subsequent work using radioactive chromium (Cr) as an erythrocyte label, showed that Ashby's data and conclusions were in fact correct, i.e. that normal erythrocytes in health circulate in the peripheral blood for approximately 110 d. Both Asby's differential agglutination method and Cr labelling have been used with brilliant effect in the investigation of patients suffering from many types of increased haemolysis. Thus, in contrast to the finding in hereditary haemolytic anaemias, e.g. hereditary spherocytosis (HS), that the life-span of transfused normal erythrocytes is normal, that of normal erythrocytes transfused to patients with an acquired immune haemolytic anaemia is characteristically shortened (Brown et al, 1944; Mollison, 1947). Erythrocyte labelling with Cr also had a further advantage over the Ashby method in addition to enabling the life-span of the patients' erythrocytes to be assessed in his or her own circulation, namely, that it was possible, by surface counting, to detect and measure the accumulation of radioactivity in the spleen and liver, i.e. the presence in the organ of the labelled erythrocytes, and thereby assess the organs' role in haemolysis (Szur, 1970).