Multifunctional roles of thrombin

Abstract

Thrombin is an unique molecule that functions both as a procoagulant and anticoagulant. In its procoagulant role it activates platelets through its receptor on the platelets. It regulates its own generation by activating coagulation factors V, VIII and even XI resulting in a burst of thrombin formation. It activates factor XI, thus preventing fibrin clots from undergoing fibrinolysis. Thrombin not only cleaves fibrinogen to fibrin, but also through the activation of factor XIII effects the cross-linking of fibrin monomers to produce a firm fibrin clot. Thrombin's role as an anticoagulant is mediated through binding to thrombomodulin, a receptor protein on the endothelial membrane of the blood vessel, initiating a series of reactions that leads to fibrinolysis. Thrombin has chemotactic properties enabling it to exert its effects during inflammation and vascular injury. It has a mitogenic effect stimulating growth of mammalian cells, fibroblasts and macrophage-like tumor cell lines. It has also been implicated in brain development. A molecule with multifunctional roles such as thrombin has its activity in vivo modulated by only a few endogenous inhibitors.

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