[Recent developments in fibrinolysis].

Abstract

Since streptokinase and urokinase became available for clinical use, numerous attempts have been made to improve these useful thrombolytic agents. In order to decrease its antigenicity, streptokinase has been fragmented or coupled to human plasminogen or polyethylene glycols. With a plasmin B-chain-streptokinase complex a more potent agent was obtained. To prolong their half-life, streptokinase and urokinase were immobilized with water-soluble carriers. Coupling urokinase or tissue-type plasminogen activator with fibrin-specific antibodies increases its thrombolytic efficiency, at least in vitro. The only thrombolytic agents with a relative fibrin-selectivity presently available for clinical purposes are tissue-type plasminogen activator and single chain urokinase-type plasminogen activator. Structural manipulation allows to design and produce mutant proteins with specific deletions, additions or substitutions of non-protease domains. Also chimaeric molecules combining fragments of tissue-type plasminogen activator and single chain urokinase-type plasminogen activator have already been constructed. These modifications of natural molecules may further improve their fibrin-specificity and therapeutic potential.