Aplastic crisis in sickle cell anemia; a study of its mechanism and its relationship to other types of hemolytic crises.

Abstract

Abstract The observation of an "aplastic" crisis which occurred during the course of clinically demonstrable virus pneumonia in a patient with sickle cell anemia is reported. On admission the patient showed reticulocytopenia, leucopenia, and erythrocytic aplasia of the marrow. Within three days the red cell level dropped to about 50 per cent of its previous level. Six days later numerous reticulocytes and nucleated red cells reappeared in the blood and the marrow had reverted to an extreme hyperplasia of the erythropoietic tissue. The "aplastic" crisis is supposedly due to the combination of absent red cell production together with an unaltered rapid elimination of the defective erythrocytes from the circulation. It was attempted to demonstrate this mechanism in our case by determination of the survival time of the patient's erythrocytes seven months after his recovery. About 50 per cent of the transfused cells disappeared within three days—a finding in close agreement with the observed elimination of about half of the red cell mass during the crisis. These results, therefore, support the above-mentioned concept of the pathogenesis of the "aplastic" crisis. Analysis of the survival time graphs of the erythrocytes of this and other patients with sickle cell anemia demonstrates that different portions of the red cell population show a variable degree of destructibility. The severity of the "aplastic" crisis will depend on the percentage of the most easily destructible cells present in the total erythrocyte population. The etiology of the erythropoietic aplasia in our patient appears to be related to the infective agent causing the pneumonia. This interpretation is supported by reported instances of familial crises in hereditary spherocytosis associated with infections and the finding of an erythroblastopenic marrow in a hematologically normal patient with virus pneumonia. The factors responsible for the variable destructibility of the erythrocytes in sickle cell anemia are discussed. It is emphasized that the recent discovery of abnormal hemoglobin in this disease does not fully explain this phenomenon. It seems necessary to postulate an additional extrinsic or intraerythrocytic factor which also contributes to the premature disintegration of these defective erythrocytes. Evidence is presented that a precipitous decrease of the red cell level in an existing hemolytic syndrome may be produced by quite different mechanisms. Three main varieties of crisis may be distinguished. (a) The " aplastic " type, caused by a sudden cessation in the delivery of cells without any exaggeration of the already accelerated hemolysis; (b) the hyperhemolytic type, induced by an abrupt augmentation of erythrocyte destruction above the precrisis level without any primary interference with production and release; and (c) the aplastic-hyperhemolytic type, a combination of absent delivery of cells associated with markedly increased hemolysis. Our case belonged in the first category. The "aplastic" crisis should, therefore, be considered as a general phenomenon occurring in various hemolytic disorders and as not limited to hereditary spherocytosis. An imminent "aplastic" crisis in a patient with a known hemolytic syndrome should be immediately suspected if the absence of polychromatic erythrocytes (reticulocytes) is noted on the film. If sufficient attention is paid to this readily detectable sign, more instances of this type of crisis may be diagnosed properly in the future.