Potentiation of the Anti-factor VIII Effect of Thrombin in Plasma by the Plasminolytic Derivatives of Fibrinogen and Fibrin

Abstract

SummaryThe activity of factor VIII in mixtures of native plasma or blood with fibrinogen derivatives at concentrations high enough to inhibit prothrombin consumption, is greatly reduced. On the other hand the activity of factor VIII was found normal in similar mixtures of adsorbed native plasma with fibrinogen derivatives, where no generation of thrombin could have taken place. The fibrinogen derivatives increased significantly the inactivating effect of low concentrations of thrombin on the activity of factor VIII of mixtures of adsorbed oxalated plasma with the derivatives. The same inactivating effect was exerted by fibrinogen derivatives heated at 60° C for 15 minutes and by plasmin lysed fibrin. In contradistinction addition of intact fibrinogen or fibrinogen derivatives to heat-defibrinated plasma protected factor VIII from inactivation by thrombin. When both, intact fibrinogen and its derivatives, were added simultaneously at the same concentrations at which they were added singly, the protective effect was intermediate between that exerted by intact fibrinogen and fibrinogen derivatives alone. Under these conditions the fibrinogen derivatives appeared as if they potentiated the inactivating effect of thrombin. Probably by inhibiting the formation of structural fibrin they increased the amount of thrombin, which remained unadsorbed and free to inactivate factor VIII.