The haematological manifestations of sepsis.
Haematological changes in the septic patient are, primarily, neutropenia or neutrophilia, thrombocytopenia and disseminated intravascular coagulation (DIC). Thrombocytopenia frequently arises from DIC although inhibition of thrombopoiesis or immunological platelet damage also occur. DIC contributes to bleeding and microvascular thrombosis, leading to multiple organ failure. Tissue factor release, primarily mediated by tumour necrosis factor, activates the clotting system; fibrinolysis is initially activated, but later becomes inhibited by the release of plasminogen-activator inhibitor (PAI-1), further fostering multiple organ failure. Most septic patients have compensated, chronic DIC, detectable by assays of molecular markers; the earliest signs are already found during the systemic inflammatory response syndrome. Compensated DIC later becomes decompensated with rapid consumption of factors including inhibitors such as antithrombin III (AT III) and proteins C and S. AT III concentrations of < 60-70% of the normal values predict outcome. Management of DIC must address the underlying disease, interrupt the activated haemostasis system and replace consumed coagulation constituents. Interruption of haemostasis with heparin may be attempted, but bleeding may worsen. Administration of a natural anticoagulant, such as AT III, may arrest clotting without concomitant risk of bleeding. In several animal models of DIC, AT III concentrates shortened the duration of DIC and reduced multiple organ failure and mortality. Similar benefits have been reported in early studies of patients with DIC, especially in the absence of sepsis. Studies are under way to determine whether outcome will improve if patients with sepsis are treated before the development of shock and plasma AT III concentrations are maintained at 100-150% of normal.
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Wayne State University School of Medicine, Mott Center, Detroit, MI 48201, USA.
D000990:Antithrombin III / Q000378:metabolism; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D006801:Humans; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000378:metabolism; D013921:Thrombocytopenia / Q000097:blood* / Q000209:etiology
D000990:Antithrombin III