Figure2 shows an algorithm for the investigation of hemolytic anemia. Whatever the cause of hemolysis, the end result is rupture and destruction of the red cell. Rupture involves membrane damage which need not be complete from the outset (except in fulminant intravascular hemolytic reactions), and so degrees of development of red cell damage may be observed in the circulating red cells. If membrane is lost evenly from the red cell, as seen in hereditary spherocytosis and autoimmune hemolysis, smooth regular hyperchromic spherocytes will be seen in the blood film. If the spherocytes are irregular fragmented cells, there may be specific morphological changes, for example Heinz body spherocytes and microangiopathic hemolytic anemia. In some hemolytic anemias the red cell morphology itself may be diagnostic (e.g. sickle cells, malarial parasites, autoagglutination).
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