Inhibitory Effect of Activated Protein C on Activation of Prothrombin by Platelet‐Bound Factor Xa

Abstract

Factor X_a binds to a receptor available on the platelet surface after the release reaction. The receptor consists of phospholipid and factor V. Factor X_a bound to the receptor catalyses the activation of prothrombin effectively. The effects of bovine protein C, a vitamin-K-dependent zymogen of a serine protease, on prothrombin activation by platelet-bound bovine factor X_a has been studied. Protein C was found to be activated (protein C_a) by thrombin formed in the prothrombin-platelet-factor X_a incubation. Protein C_a in contrast to the zymogen, protein C, or protein C_a inactivated with diisopropylphosphofluoridate inhibited prothrombin activation by factor X_a in the presence of platelets. Protein C_a was found to destroy the receptor by proteolysis whereas direct binding of protein C_a to the receptor could not be demonstrated. The inhibition by protein C_a could be monitored as a parallel decrease in factor X_a binding and prothrombin activation. The receptor was protected by factor X_a from proteolysis by protein C_a. Protein C_a was also found to inhibit the interaction between prothrombin and the factor X_a platelet receptor. These results indicate that protein C after activation may have a role as a regulator of prothrombin activation in vivo.