IMPAIRMENT OF PLATELET-AGGREGATION IN HEMOLYTIC UREMIC SYNDROME - EVIDENCE FOR PLATELET EXHAUSTION

Abstract

Thrombocytopenia, microangiopathic hemolytic anemia and acute renal failure are the hallmarks of hemolytic-uremic syndrome (HUS). The results of platelet studies from 10 consecutive HUS patients in childhood are presented. During their acute illness, they all displayed a characteristic pattern of impaired platelet function: no aggregating responses to epinephrine, some to ADP and moderate to collagen. Platelet contents of .beta.-thromboglobulin (.beta.TG) were markedly reduced. As these patients improved clinically, their platelet-aggregating responses also normalized despite their uremic state. Incubation of platelets with uremic plasma or guanidinosuccinic acid, a uremic toxin, had minor effects on platelet-aggregating activity. Since low levels of platelet .beta.TG suggest that these platelets were in an exhausted state, in vitro experiments were performed to exhaust normal platelets by incubation at 37.degree. C. A proportional impairment of platelet-aggregating responses and decreasing levels of platelet .beta.TG were noted. The pattern of impairment was similar to that found in the platelet-aggregating activities of HUS patients. Exhaustion, in addition to azotemia and thrombocytopenia, are factors that contribute to the functional impairment of platelets in these patients. Further studies to reveal mechanisms that lead to platelet exhaustion in HUS are of fundamental importance in the understanding of this illness.