Role of platelet activation and fibrin formation in thrombogenesis

Further progress in the search for more effective but safe antithrombotic agents is coupled to an improved understanding of the factors involved in arterial and venous thrombogenesis. Although arterial thrombosis is initiated by formation of a layer of platelets on modified endothelium or subendothelial constituents and subsequent recruitment of passing-by platelets, this phenomenon is not sufficient to lead to a full thrombus. Further growth of such a platelet mass depends, to a large extent, on the presence of free thrombin. Thrombin is mainly generated by activation of factor XI on the platelet contact with collagen. In addition, thrombin leads to formation of fibrin, which maintains the stability of the arterial platelet thrombus and is the main component of the venous thrombus. The search for agents that inhibit platelet activation and thrombin formation is, therefore, a logical endeavor