Summary. Several of the disease states in which red‐cell fragments appear in the peripheral blood have features suggestive of intravascular coagulation with fibrin deposition in vessels. As this process might be a cause of red‐cell fragmentation the interaction of rapidly moving red cells with fibrin strands was investigated. Red cells arrested on fibrin strands while moving through a loose fibrin clot at the velocity of arterial blood flow were bent over the strands by the force of blood flow and eventually fragmented. The shape of the fragments which resulted depended upon the position and plane in which the red cells were arrested, the point at which the membrane ruptured, the distribution of haemoglobin and membrane between the resulting fragments and finally on whether or not crenation of the fragments supervened. Systems in which red cells perfused artificial ‘clots’ of glass fibre and nylon also caused the red cells to fragment. The fragmentation process seems to depend, therefore, on a rapid blood flow and the arrest of individual red cells by any obstruction of small dimensions, e. g. by strands or spikes less than I p in diameter. It was concluded that these conditions were most likely to obtain in vivo as the result of intravascular deposits of fibrin in the lumen of small arterioles.

The response of three children and four adult women with microangiopathic haemolytic anaemia to treatment with heparin is described. The one child and three adults treated within 10 days of the onset of the illness recovered rapidly and completely from their anaemia, thrombocytopenia and uraemia. The two children and one adult treated between 18 and 31 days after the onset of the illness responded less well. The two children who were given small doses of heparin died from complications of the renal microangiopathy despite improvement in the haemolysis and thrombocytopenia. The adult woman made a slow and partial recovery; the haemolysis and thrombocytopenia improved, but renal function did not return to normal.The importance of recognizing and treating the low grade intravascular coagulation which may accompany microangiopathic haemolytic anaemia is stressed. It is suggested that the variable response to treatment with heparin of patients with microangiopathic haemolytic anaemia observed by ourselves and others may be due to relative roles of intravascular coagulation and primary vascular disease in the pathogenesis of the microangiopathy, and to the development of irreversible vascular damage if treatment is delayed.

Summary. In rabbits transient haemoglobinaemia accompanied rapid defibrination produced by the purified coagulant fraction of the venom of the Malayan pit‐viper, Agkistrodon rhodostoma. The degree of haemoglobinaemia was dependent upon the rate of defibrination. Inhibition of fibrinolysis resulted in the persistence of the haemoglobinaemia after venom defibrination. Irradiation to produce thrombocytopenia or anticoagulation enabled these rabbits to survive more rapid rates of defibrination and resulted in prolonged haemoglobinaemia (due to continuing haemolysis) and the appearance of fragmented red cells. Haemoglobinaemia was associated with the occurrence and persistence of a network of loose fibrin to which red cells were adherent both free in the circulation and fixed in blood vessels. It is suggested that haemolysis and red‐cell fragmentation result from the interaction of red cells with porous fibrin thrombi, and that this interaction occurs in human disease and is the causal mechanism of microangiopathic haemolytic anaemia.