Natural anticoagulation mechanisms

There are two major anticoagulation pathways based around antithrombin III, a serine protease, and the vitamin-K-dependent protein C-protein S pathway. Antithrombin III is a potent inhibitor of thrombin and factor Xa, and can also inactivate factors IXa, XIa, and XIIa. It action is greatly potentiated by heparin or heparan sulfate and represents the mechanism by which heparin exerts its anticoagulant effect. Thrombin activates protein C through its interaction with thrombomodulin, a receptor on the vascular endothelium. Activated protein C in conjunction with protein S exerts its anticoagulant activity by enzymatic cleavage of factors Va and VIIIa which are important cofactors in the procoagulant pathway. Protein C also enhances the fibrinolytic system by protecting tissue plasminogen activator from inhibitors, resulting in enhanced conversion of plasminogen to plasmin. Specific antigenic and functional assays have been designed to detect abnormalities of these anticoagulant proteins. Protein C may play an important role in the pathogenesis of disseminated intravascular coagulation (DIC). Quantitative and functional defects of antithrombin III, protein C, and protein S are associated with a high incidence of thrombosis.

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