The factor VIII-independent activation of factor X by factors IXa and VII in plasma

The requirements for the activation of factor X by factors IXa and VIII were studied in plasma and in a system consisting of purified clotting factors. In the purified clotting factors system, factor IXa did not activate factor X unless factor VIII was also present. In contrast, the addition of factor IXa to either severe hemophilic or factor VIII-immunodepleted plasma resulted in significant activation of factor X. Factor X activation by factor IXa in plasma severely deficient in both factor VII (congenital) and factor VIII (immunodepletion) was greatly reduced compared with plasma deficient only in either factor VII or factor VIII. The addition of factor VII to plasma deficient of both factors VII and VIII restored the ability of the factor IXa to activate factor X. The addition of anti-factor-VIIIc did not diminish the activation of factor X by factor IXa in severe hemophilic plasma or factor VIII-depleted plasma. These observations suggest that in the absence of factor VIII and added tissue factor, the activation of factor VII by factor IXa provides the principal pathway for the activation of factor X.