In response to vascular injury, platelets adhere to the exposed vascular extracellular matrix, become activated, and form a thrombus. The activated platelet surface is procoagulant and promotes the generation of thrombin. COMP circulates in plasma and is locally released from, and synthesized by, activated platelets, where it functions as an endogenous inhibitor of thrombin, inhibiting the conversion of fibrinogen to fibrin and limiting the degree of thrombin-induced platelet activation through PAR receptors. COMP binding to thrombin occurs through thrombin exosites I and II.