THROMBOLYTIC AGENTS - AN OVERVIEW

Thrombolysis today has become a routine option not only in the treatme nt of acute myocardial infarction but also in many other manifestation s of thromboembolic disease. Until one decade ago, only two plasminoge n activators, streptokinase and urokinase, were available for clinical use. They were characterized by limited thrombolytic potencies and ma jor side effects including systemic fibrinogen breakdown, bleeds and s troke. This has promped the searche for new plasminogen activators wit h better pharmacological and clinical profils, The first such new plas minogen activators were Anistreplase, a chemically modified version of the streptokinase-plasminogen-activator-complex and tissue-type plasm inogen-activator produced by recombinant technology. Both new substanc es have fuelled the development in modern thrombolytic treatment. Whil e the clinical progress with t-PA was confirmed in large, double-blind , randomized, multicenter trials, no real superiority of anistreplase over the traditional plasminogen activators urokinase and streptokinas e has been substantiated. While the clinical use of t-PA today has bee n been established for acute myocardial infarction, pulmonary embolism and deep vein thrombosis, current researche is focused on further pla sminogen activators with further improved thrombolytic properties. Thi s review summerizes the current knowledge on the biochemical and pharm acological properties of the first, second and futur generation of pla sminogen activators.