EXPERIMENTAL STUDIES IN THROMBOLYSIS AND FIBRINOLYSIS

New approaches to further improve thrombolytic therapy include strategies to enhance the fibrinolytic potency of plasminogen activators and to improve conjunctive antiplatelet or antithrombotic agents. The fibrinolytic potency of plasminogen activators may be enhanced by the construction of mutant and chimeric molecules and of antibody-targeted plasminogen activators. Antiplatelet strategies include the use of platelet glycoprotein IIb/IIIa receptor blocking agents, thromboxane synthase inhibitors, and endoperoxide receptor antagonists. Antithrombotic strategies include the use of more selective thrombin inhibitors and inhibitors of tissue factor or of factor Xa. Several of these conjunctive strategies were shown to contribute to the prevention of platelet-rich arterial thrombosis, the acceleration of clot lysis with thrombolytic agents, and the reduction of reocclusion in animal models of thrombosis. The safety of these strategies in humans, particularly with respect to the bleeding risk that may be associated with the use of more potent antiplatelet or antithrombotic agents, will require careful evaluation.