Role of new anticoagulants as adjunctive therapy during thrombolysis

Procoagulant activity may persist during coronary thrombolysis and result in either delay in the time to recanalization or recurrent thrombosis. Although heparin and aspirin form the mainstay of current therapy, recurrent thrombosis occurs despite adjunctive heparin therapy during thrombolysis. Newer agents that inhibit thrombin by antithrombin III-independent mechanisms, or that inhibit earlier steps in the coagulation cascade, have been shown to be effective in the experimental preparation of coronary thrombolysis. Because heparin-antithrombin III is a relatively inefficient inhibitor of thrombin bound to fibrin, agents such as hirudin or small peptide inhibitors of the thrombin-active site appear to be more effective inhibitors of clot-associated thrombin activity. Inhibition of early steps in the coagulation cascade with the inhibitor of tissue factor-factor VIIa complex, or with activated protein C, also appears to be an effective anticoagulant strategy. In experimental preparations all of these agents have shown superiority in preventing recurrent thrombosis compared with heparin, and in some cases they appear to accelerate the rate of clot lysis.