[The fibrinolytic system and its activators].

Abstract

The human fibrinolysis system is a proteolytic enzymatic process in the blood. Its purpose is to locally limit intravascular thrombotic processes and to reopen vessels closed by thrombosis. The main enzyme of the fibrinolysis system is the active protease plasmin produced by activation of the inactive first step plasminogen by means of plasminogen activators via limited proteolysis. Thrombolytic therapy with plasminogen mimics and enhances physiological fibrinolysis. The following substances are presently available for clinical use: the non-physiological thrombolytics streptokinase and APSAC (acylated plasminogen-streptokinase activator complex), as well as the physiological plasminogen activators urokinase and tissue plasminogen activator (t-PA). Whereas the first three systemically activate the fibrinolysis system, t-PA possesses relative fibrin selectivity. The fibrin-selective active prourokinase and a recombinant mutant of t-PA with prolonged in vivo half-life have not yet been officially approved for the treatment of thromboembolytic diseases but are being clinically tested. In the development stage are mutants, hybrid enzymes and conjugates aiming at further improvement of this therapeutic concept by means of changing the half-life, thrombus affinity and thrombolytic activity. The development of highly effective antithrombotics will help to further improve the results of thrombolytic therapy.