Annales de biologie clinique vol:45 issue:2 pages:198-201
Tissue-type plasminogen activator (t-PA) is a serine protease with a molecular weight of about 70,000. It activates plasminogen to plasmin by cleavage of the Arg 560-Val 561 peptide bond. Kinetic analysis showed that the activation obeys Michaelis-Menten kinetics and that the presence of fibrin strikingly enhances the activation rate. The directed action of plasmin towards fibrin in vivo can be explained by the low Michaelis constant in the presence of fibrin (0.16 microM) which allows efficient plasminogen activation on a fibrin clot, while its high value in the absence of fibrin (65 microM) prevents efficient activation in plasma. Plasmin formed on the fibrin surface is protected from rapid inactivation by alpha 2-antiplasmin. Studies on the thrombolytic properties of t-PA (purified from melanoma cell cultures or obtained by recombinant DNA technology) in various animal models and in selected patients revealed that t-PA is a specific thrombolytic agent which induces thrombolysis without causing extensive systemic activation of the fibrinolytic system.