Impaired and exhausted platelets in modified generalized Shwartzman reaction: an analogue of hemolytic uremic syndrome associated with endotoxemia.
Thrombocytopenia is characteristically associated with septicemia and hemolytic uremic syndrome (HUS), a subset of which has been shown to be associated with endotoxemia and shigellosis. An experimental model that closely resembles these clinical conditions is the generalized Shwartzman reaction modified with a continuous intravenous infusion of endotoxin for 5 hr in rabbits. In addition to exhibiting the triad of HUS (thrombocytopenia, hemolytic anemia, and azotemia), these animals also had circulating platelet aggregates, leukocytosis, lipidemia, hemoglobinemia, hyperfibrinogenemia, and prolonged partial thromboplastin time. Platelets that remained in circulation were chemically exhausted in serotonin content and functionally impaired in aggregation activities. Plasma from animals during thrombocytopenia and platelet functional deficiency had no effect of the aggregation responses of normal platelets. Although the single triggering event of endotoxin infusion was stopped at hour 5, recovery from abnormalities was only partial on day 2 and within normal limits by day 3. In vitro studies supported platelet exhaustion as a mechanism for decreased platelet function after endotoxin infusion. The presence of circulating platelet aggregates and exhausted platelets suggested that the process of platelet activation took place at as long as 24 hr after the cessation of LPS infusion. Endotoxin and other mechanism(s) are likely to be operative in the pathogenesis leading to platelet activation. Further studies to reveal the mechanism of platelet exhaustion in the experimental model may help our understanding of corresponding events in clinical endotoxic injury and HUS associated with endotoxemia.
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D004731:Endotoxins / Q000097:blood*; D006463:Hemolytic-Uremic Syndrome / Q000097:blood*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology; D008297:Male; D010974:Platelet Aggregation; D011817:Rabbits; D012701:Serotonin / Q000097:blood; D013921:Thrombocytopenia / Q000097:blood
D004731:Endotoxins; D008070:Lipopolysaccharides; D012701:Serotonin