Y. Katsuura et al., CHARACTERISTIC EFFECTS OF ACTIVATED HUMAN PROTEIN-C ON TISSUE THROMBOPLASTIN-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION IN RABBITS, Thrombosis research, 76(4), 1994, pp. 353-362
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.