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Thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure are the hallmarks of hemolytic-uremic syndrome (HUS). This report presents the results on platelet studies from 10 consecutive HUS patients in childhood. 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. In addition, 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 guanidino-succinic 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 degrees C. A proportional impairment of platelet-aggregating responses and decreasing levels of platelet beta TG were noted. Furthermore, the pattern of impairment was similar to that found in the platelet-aggregating activities of HUS patients. Thus, “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.

The Shwartzman phenomenon may be defined as the pathologic manifestation of disseminated intravascular coagulation with widespread hemorrhagic necrotic lesions and bilateral renal cortical necrosis induced by the administration of two spaced injections of endotoxic lipopolysaccharide (LPS).I Results of previous investigations indicate that the platelet-LPS interaction with subsequent platelet adherence and release of its contents is primarily responsible for the pathologic alterations of the coagulation system (1--6). Prior treatment of rabbits which renders them thrombocytopenic or leukopenic can regularly protect these animals from the manifestation of Shwartzman lesions (7,8). Stetson found that there was a temporal correlation between thrombocytopenia and the deposition of platelet aggregates in the lung, liver, and spleen after the administration of LPS (1). Furthermore, McKay and Shapiro observed that LPS-induced thrombocytopenia corresponded well with the appearance of a hypercoagulable state (2). Recently, Mustard et al. demonstrated the protection of rabbits from Shwartzman lesions by treatment with acetylsalicylic acid, sulfinpyrazone, or phenyl butazone which are agents that interfere with the platelet release reaction (9-11).Although the mechanism of platelet-LPS interaction remains to be elucidated, Siqueira and Nelson suggested that the complement system is important in this interaction (12). Review of recent reports indicates that plasma factors are required for the platelet-LPS interaction and that these factors are inhibited

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