Summary
Although protein C (PC) and activated protein C (APC) have been postulated to be useful
for treating patients with thrombosis, their critical effect remains to be studied
in human subjects. To examine whether purified PC or APC are useful for treating patients
with thrombosis without showing any adverse effect, wc studied effects on coagulation
and fibrinolysis in normal human subjects.
When highly purified human PC was administered intravenously to healthy subjects,
plasma levels of immunoreactive PC decreased with a half-life of 10.9 h. Intravenously
administered APC decreased with a half-life of 23 min as measured by prolongation
of activated partial thromboplastin time (APTT). However, 1.7 h was obtained for the
plasma half-life of APC when it was measured immunologically. These findings suggested
that a significant fraction of the administered APC was rapidly inhibited by plasma
inhibitor. Upon administration of APC, APTT was prolonged and plasma levels of clotting
factor VIII (FVIII) decreased transiently as measured by clotting assay. However,
when determined by a chromogenic assay method in which 120-fold diluted plasma samples
were used, plasma levels of FVIII remained unchanged. Plasma levels of F-V did not
decrease after APC administration. These findings suggested that prolongation of APTT
and apparent decrease in plasma F-VIII clotting activity might be due to the in vitro-effect
of APC present in plasma samples used. Diurnal fluctuation of plasminogen activator
inhibitor in normal subjects was not affected by administration of APC.
Thus, PC or APC seems to function selectively at the site of thrombin-formation without
lowering plasma levels of coagulation factors.
Keywords
Protein C - Thrombosis - Factor V - Factor VIII - Plasminogen activator inhibitor
