CHARACTERISTIC EFFECTS OF ACTIVATED HUMAN PROTEIN-C ON TISSUE THROMBOPLASTIN-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION IN RABBITS

Protein C (PC) is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C : APC) by thrombi n in the presence of thrombomodulin. APC plays an important role in re gulating thrombosis and fibrinolysis by inhibiting not only blood coag ulation factors Va and Villa but also type-1 plasminogen activator inh ibitor (PAI-1). In the present study we examined the effects of human APC on tissue thromboplastin-induced disseminated intravascular coagul ation (DIC) in rabbits and compared them with those of heparin. Both A PC (300-3000 U/kg) and heparin (100-300 IU/kg) inhibited the decreases in platelet count and fibrinogen level equally. APC improved the prol onged bleeding time, but heparin aggravated bleeding with potent prolo ngation of activated partial thromboplastin time (APTT). Furthermore, in APC-treated animals, fibrin deposition in glomeruli was less than i n heparin-treated animals. This result suggests that APC accelerated l ocal fibrinolysis by neutralizing PAI-1. From our findings, we conclud ed that APC can improve both coagulation and fibrinolysis in a DIC mod el and should be useful for the clinical remedy of DIC without having an adverse side effect like a bleeding tendency.