EXPERIMENTAL STUDIES IN THROMBOLYSIS AND FIBRINOLYSIS

New approaches to further improve thrombolytic therapy include strateg ies to enhance the fibrinolytic potency of plasminogen activators and to improve conjunctive antiplatelet or antithrombotic agents. The fibr inolytic potency of plasminogen activators may be enhanced by the cons truction of mutant and chimeric molecules and of antibody-targeted pla sminogen activators. Antiplatelet strategies include the use of platel et glycoprotein IIb/IIIa receptor blocking agents, thromboxane synthas e inhibitors, and endoperoxide receptor antagonists. Antithrombotic st rategies include the use of more selective thrombin inhibitors and inh ibitors of tissue factor or of factor Xa. Several of these conjunctive strategies were shown to contribute to the prevention of platelet-ric h arterial thrombosis, the acceleration of clot lysis with thrombolyti c agents, and the reduction of reocclusion in animal models of thrombo sis. The safety of these strategies in humans, particularly with respe ct to the bleeding risk that may be associated with the use of more po tent antiplatelet or antithrombotic agents, will require careful evalu ation.