In recent years, thrombolytic therapy has become widely used in patients with acute myocardial infarction. Indeed, thrombolytic agents have been shown to induce reperfusion of the occluded coronary arteries, save ischemic myocardium, improve left ventricular dysfunction, and enhance both early and late survival. In contrast, the use of thrombolytic agents remains controversial and infrequent in other thromboembolic diseases, such as venous thromboembolism, peripheral obstructive arterial disease, and unstable angina, mainly because of the fear of a negative benefit-risk ratio.
Most experience with thrombolytic agents in venous thromboembolism is with streptokinase and urokinase, the first-generation plasminogen activators. Streptokinase and urokinase have little affinity for fibrin. They activate both circulating and thrombus-bound plasminogen, which results in systemic plasmin generation and, consequently, in a severe hemostatic defect, which could contribute to the hemorrhagic complications of thrombolytic therapy. Tissue-type plasminogen activator (t-PA), a second-generation thrombolytic agent, has high affinity for fibrin and is activated by fibrin. In the absence of fibrin, t-PA activates plasminogen at a very slow rate; however, in the presence of fibrin or fibrin fragments, the rate of plasminogen activation is accelerated a hundredfold.
Studies in animal models have shown that recombinant t-PA (rt-PA), in contrast with streptokinase, has the potential to induce thrombolysis without producing a systemic lytic state. Thus, it was originally hoped that the avidity of t-PA for fibrin and its modest impact on the hemostatic system would result in fewer bleeding complications than occur with first-generation thrombolytic agents. However, both animal and clinical studies have demonstrated that the thrombus specificity of rt-PA is dose-dependent and that rt-PA doses required for effective and rapid thrombolysis induce systemic fibrinolysis.
Category: Venous Thromboembolism
Tags: thrombolysis, thrombolytic agent, venous thromboembolism
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