THROMBIN GENERATION INDUCED BY THE INTRINSIC OR EXTRINSIC COAGULATIONPATHWAY IS ACCELERATED BY STREPTOKINASE, INDEPENDENTLY OF PLASMINOGEN

Thrombolytic therapy paradoxically induces the formation of fibrinopep tide A, fibrin degradation products and thrombin-antithrombin complexe s, indicating thrombin generation. Part of the mechanism of this throm bin generation under the influence of thrombolytic agents was unravele d in this study. We measured thrombin with a chromogenic substrate at several time intervals after recalcification of citrated plasma which had been preincubated with urokinase, streptokinase, recombinant tissu e plasminogen activator (rt-PA) or recombinant single-chain urokinase- type plasminogen activator (rscu-PA). Thrombin generation induced by t he addition of thromboplastin together with calcium (extrinsic pathway ) was greatly accelerated in the presence of streptokinase (from about 7 to 2 min), and to a lesser extent in the presence of urokinase, rt- PA or rscu-PA. Similar effects were seen after the addition of. calciu m to the plasma containing the thrombolytic agent and preincubated wit h partial thromboplastin (intrinsic pathway). Hirudin quenched the con version of the chromogenic substrate completely, confirming that throm bin was the active enzyme. Aprotinine did not affect the results, and the effect of streptokinase was also observed in plasminogen-depleted plasma. We conclude that streptokinase, and to a lesser extent other t hrombolytic agents, activate the prothrombinase complex directly or in directly through a calcium-dependent mechanism, independently of plasm inogen, with a resulting acceleration of thrombin generation.