Thrombolytic therapy in stroke: possibilities and hazards.

Abstract

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

Intravenous Thrombolytics for Ischemic Stroke

“…Despite these limitations, very important work was independently completed and somein collaboration by del Zoppo et al [29], Zeumer [34], and Mori et al [35] demonstrating the angiography evidence of arterial occlusion and response to fibrinolytic therapy in patients suffering large vessel occlusion. Authors del Zoppo et al [36] treated 4 patients suffering from proximal intracranial occlusions with local infusion of streptokinase. Two patients were recanalized with marked clinical improvement, which did not occur in the absence of recanalization.…”

Interventional Neuroradiology

“…128 Using this selective delivery of urokinase, the posttreatment rate of hemorrhage has been reduced to 13%. 129 In one study, a series of patients with acute internal carotid or middle cerebral artery occlusion were classified into three categories based on the location of the occlusion. '30 The patients who had a patent circle of Willis and lenticulostriate arteries and those with distal middle cerebral artery occlusions did better than patients with occlusion of these areas.…”

The Kringle-2 domain of tissue plasminogen activator significantly reduces mortality and brain infarction in middle cerebral artery occlusion rats

“…Because of the considerable risks of cerebral hemorrhage, edema and excitotoxicity (1)(2)(3), TPA must be used within 3 h of the onset of symptoms (4). As a multi-domain serine protease, TPA consists of a finger (F), epidermal growth factor-like (G), two Kringle (K1, K2), and C-terminal serine protease (P) domains.…”