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). 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 oxidative stress induced in vivo by Shiga toxin-2 contributes to the pathogenicity of haemolytic uraemic syndrome

“…7a). This phenomenon has been described in humans and HUS mouse models as 'exhausted' platelets [22,29]. NAC and SEC treatments commenced 48 h before Stx2 injection partially restored the level of response to in-vitro stimulation (Fig.…”

“…In fact, although PMN from HUS children on admission show impaired ROS production after direct protein kinase C stimulation [35], it has been suggested that they are low responders as a consequence of a previous activating process, which triggered the respiratory burst and the release of proteases associated with degranulation [4,35]. This process is similar to that found for platelets that circulate in a degranulated form as a consequence of a strong thrombotic stimulus prior to hospitalization [29,36].…”

Activated platelet aggregates in thrombotic thromboctyopenic purpura: decrease with plasma infusions and normalization in remission

“…Previous publications reported impaired aggregation and secretion of platelets from patients with haemolytic uraemic syndromes, a disorder similar to TTP in pathophysiology, and suggested that platelets were exhausted by prior in vivo activation (Kaplan & Fong, 1980;Fong & Kaplan, 1982;Walters et al, 1988). However, a recent study employing CD62p as an activation marker failed to find evidence of platelet activation in TTP (Hoffman et al, 1993).…”

Cancer associated haemolytic uraemic syndrome developing prior to treatment with cytotoxic agents

“…While thrombocytopenia is not invariable in HUS, it was nonetheless surprising that thrombocytopenia was never evident other than following the course of chemotherapy. Fong and Kaplan have suggested that platelets become "exhausted" through activation in the microcirculation [20], and it is likely they are subsequently taken up by the reticulo-endothelial system [2 11. It may therefore be reasonable to speculate that the extent of the microangiopathy determines the severity of the thrombocytopenia, implying that in this instance it was not widespread.…”