Pathophysiology of disseminated intravascular coagulation in sepsis

Disseminated intravascular coagulation (DIC) is an acquired syndrome charac terized by intravascular fibrin formation occurring in the course of a vari ety of severe diseases. In Gram-negative sepsis, endotoxin is the bacterial component eliciting a cascade of tissue factor dependent hypercoagulable r eactions mediated by cytokines, including tumor necrosis factor-or and inte rleukin-6. Fibrinolysis is activated in this process by the action of tumor necrosis factor-at, but its activity is impaired by the predominant inhibi tory effect of plasminogen activator inhibitor-1. Natural inhibitory mechan isms include antithrombin, the protein C system, and tissue factor pathway inhibitor. Each of these defense systems counteracts the harmful effects of DIC, and its acquired deficiency is associated with increased mortality in observational studies. The generation of several proteases in DIC, including factor Xa and thrombi n, has potential interactions with inflammatory pathways that may potentiat e the systemic inflammatory syndrome that often accompanies Die. Experiment al studies support the notion that defects in the protein C pathway modulat e the inflammatory response, and illustrate that coagulation and inflammati on are coupled systems inDIC.