AGQ^UIRED HAEMOLYTIC ANAEMIAS 



an important point in considering the pathogenesis of 

 haemolytic anaemia. 



There are two possibiUties. (i) The antigenicity of the red 

 cells has been modified by viruses, drugs or toxins, so that 

 they can now provoke a normal antibody-producing me- 

 chanism to produce antibody against these new determinants. 

 In terms of the clonal selection theory, new determinants 

 have appeared on the red cells which were not present at 

 a time when the corresponding clones could have been 

 eliminated. 



The evidence speaks strongly against this. The antibodies 

 present react with red cells other than those of the patient 

 and can be shown to react with known antigens, often in 

 the Rh group. Even the 'non-specific' antibodies which 

 react with all but the rare -D-j-D- genotype seem to 

 correspond to a definable antigen. The suggestion often made 

 that a virus may modify the cells to a new antigenicity has a 

 small experimental basis (Burnet and Anderson, 1947), but it 

 seems most unlikely that it plays any part in human disease. 



(ii) The second possibility is that the antibodies represent 

 the development of abnormal serum proteins, and this is the 

 view to which Dacie inclines. On the clonal selection hypo- 

 thesis we postulate somatic mutation giving rise to new 

 patterns which are 'accidentally' appropriate to react with 

 red cell determinants present in the body. Findings which 

 can be regarded as favourable to this viewpoint are: 



(a) There is frequently an abnormally high gamma 

 globulin concentration in the blood. 



{b) The antibodies present may react with known anti- 

 genic determinants on the red cells and they will react 

 as readily with cells from other persons of the same 

 blood type as with the patient's own cells. 



{c) Thrombocytopenia is often associated with these 

 conditions. 



{d) The agglutinins present are usually incomplete and 

 often 'cold'. 



127 



