Thrombolytic therapy.

Abstract

Thrombolytic agents are plasminogen activators that convert plasminogen, the inactive proenzyme of the fibrinolytic system in blood, to the proteolytic enzyme plasmin. Plasmin in turn dissolves the fibrin of a blood clot, but may also degrade normal components of the hemostatic system and predispose to bleeding. The first-generation thrombolytic agents, streptokinase and urokinase, are only moderately efficacious, and their administration is associated with extensive systemic fibrinogen breakdown. In three major clinical trials in patients with acute myocardial infarction, early intravenous streptokinase significantly reduced in-hospital mortality. Tissue-type plasminogen activator (t-PA) is a more effective and fibrin-specific coronary arterial thrombolytic agent than streptokinase, but its impact on mortality remains to be established. Single-chain urokinase-type plasminogen activator (scu-PA, pro-urokinase) is more fibrin specific than urokinase but has only reached the stage of early clinical investigation. The acylated plasminogen streptokinase activator complex (Apsac) has a profile of thrombolytic efficacy and fibrin specificity that is probably very similar to that of streptokinase, but it can be administered as a single bolus injection. New trends toward further improved efficacy and fibrin specificity of thrombolytic therapy include the use of combinations of synergistic thrombolytic agents, mutants of t-PA or scu-PA, chimeric t-PA/scu-PA molecules, or antibody-targeted thrombolytic agents.