Factor IXa protects activated factor VIII against inactivation by activated protein C.

The effect of activated protein C on human coagulation factor VIII was evaluated by studying its effect on the intrinsic factor X activation using a system of purified coagulation factors (factor IXa, factor X, factor VIII, activated protein C). Activated protein C had no effect on the activation of factor X by factor IXa in the absence of factor VIII. In the presence of thrombin activated factor VIII the rate of factor X activation was decreased by activated protein C in a dose dependent way. The presence of factor IXa during the preincubation of factor VIII with activated protein C was found to protect the factor VIII against inactivation. The results suggest that activated protein C and factor IXa compete for the same part of the factor VIII molecule.