The sepsis-coagulant axis: a review

Abstract

Activation of coagulation is a normal component of the acute inflammatory response. Inflammatory cytokines initiate coagulation events locally at sites of inflammation by converting endothelium from an antithrombotic surface to a prothrombotic surface; by stimulating tissue factor production, which activates both the extrinsic and intrinsic coagulation systems; and by stimulating production of platelet-activating factors. The fibrinolytic system is initially activated but is subsequently inhibited. This results in a marked imbalance in coagulation and fibrinolysis resulting in a net procoagulant state. When thrombin generation and platelet activation exceed the body's capacity to inactivate or remove these factors, disseminated intravascular coagulation (DIC) results. DIC directly contributes to multiple organ failure and death associated with sepsis. Presently available treatments (i.e., heparin and aspirin) are relatively ineffective in treating DIC; however, newer, more potent drugs may soon be available for clinical use.