Thrombolytic therapy in cerebrovascular disease.

T he possible value of fibrin-selective throm- bolytic agents in acute stroke is the subject of significant current interest.1 -3 In addition to their use in acute thrombotic and thromboembolic stroke, plasminogen activators have been used to achieve vascular recanalization in selected patients with superior sagittal sinus thrombosis and acute retinal vascular thrombosis. Thrombosis and Cerebrovascular Ischemia Thrombus FormationArterial 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.4 -6 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.7 -9 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.4 These processes may be most important in microvascular thrombus formation and the blocking of reperfusion in ischemic microvascular beds.10 -12 Thrombus DissolutionAgents with thrombolytic activity are classified as endogenous or exogenous in origin.Thrombus