Thrombolytic Therapy in Cerebrovascular Disease

Arterial thrombosis and thrombus extension involve the overlapping systems of endothelial cell reactivity, platelet function, and coagulation. Thrombotic cerebrovascular occlusions arise secondary to thromboembolism from more proximal sites, e.g., the heart and proximal internal carotid artery, or from in situ thrombosis. Thrombus generation and extension involve thrombin-mediated fibrin formation and platelet activation.The early stages of intrinsic coagulation that lead to thrombin formation require the presence of a platelet-dependent factor XI receptor, high-molecular-weight kininogen, and platelet phospholipid (mediating factor V/VIII activation of factor X to Xa). Thrombin-mediated fibrinogen cleavage is accelerated by factor Xa bound to its platelet receptor (Va), promoting fibrin network formation in the thrombus.Endothelial cell ischemia or disruption promotes platelet aggregation and thrombus formation by disturbance of endothelial antithrombotic mechanisms, exposure of the subendothelium, induction of contact activation of the coagulation system, and granulocyte adherence. These processes may be most important in microvascular thrombus formation and the blocking of reperfusion in ischemic microvascular beds.-