Fibrinolysis

Abstract

The activity of the fibrinolytic system is regulated by activators and inhibitors. The inactive zymogen plasminogen, upon activation by the tissue-type plasminogen activator (t-PA) or by the urinary-type plasminogen activator (u-PA or urokinase) is converted to plasmin, a protease which degrades fibrin into soluble fibrin degradation products (Fig. 1). t-PA is synthesized by endothelial cells and is continuously released into the blood stream; its release can be considerably enhanced by many agents, acidosis and hypoxia [1]. In human blood, t-PA exists in two forms: in a free, single-chain form (sct-PA) and in an inactive form bound to the plasminogen activator inhibitor type 1 (PAI-1). Small amounts of plasmin convert sct-PA to twochain t-PA (tct-PA). The other PA, u-PA, exists in human blood as a true inactive zymogen in single-chain form (scu-PA or pro-urokinase). It can be converted to the active two-chain form (tcu-PA; urokinase) by trace amounts of plasmin or of kallikrein. Beside PAI-1 which inhibits both forms of t-PA and urokinase (but not prourokinase) another inhibitor, a₂-antiplasmin, rapidly inactivates free plasmin.