patients with various thrombolytic agents, and to weigh the relative risk of intracerebral hemorrhage in patients treated with fibrinolytic agents for stroke and for other thrombotic disorders.
Mechanism of ThrombolysisArterial thrombosis and thrombus extension involve to varying degrees the processes of endothelial injury, platelet aggregation and release, and thrombin generation. Thrombin-mediated fibrinogen cleavage results in fibrin formation which is required for thrombus stabilization.80 Thrombin-mediated fibrin formation occurs in direct relation to platelet activation by several mechanisms. Platelets promote activation of the early stages of intrinsic coagulation by a process that involves a factor XI receptor and high molecular weight kininogen.81 Also, factors V and VHI interact with platelet membrane phospholipids to facilitate the activation of factor X to Xa and the conversion of prothrombin to thrombin.82 Platelet-bound thrombinmodified factor V (factor Va) serves as a high affinity platelet receptor for factor Xa. 83 Consequently, the rate of thrombin generation is accelerated 10 3 fold, providing a potent positive feedback mechanism for initiation of thrombin formation on the platelet surface, fibrin network formation in the thrombus, and indirectly, fibrinolysis.Thrombus dissolution is, in large part, mediated by fibrinolysis localized within the thrombus.84 " 86 Fibrin (and fibrinogen) degradation is catalyzed by plasmin, the product of plasminogen activation. 87 In the consolidating thrombus plasminogen binds to fibrin and to platelets, allowing local release of plasmin within the thrombus. The circulating plasminogen activators, tissue plasminogen activator (tPA) and single chain urokinase plasminogen activator (scuPA), catalyze plasby guest on