Fibrinogen and its derivatives: cofactors in the intrinsic generation of thrombin

The simultaneous additon of suboptimal concentrations of factor VIII and intact or plasmin-lysed fibrinogen into mixtures of the vitamin K dependent factors, phospholipids, adsorbed bovine serum (supplier to factor V) and calcium, increased the amount of thrombin which was generated three to twenty times over the sum of the amounts which were generated when factor VIII, or fibrinogen, or its derivatives were added separately into the thrombin generating mixture. When factor VIII was added together with both fibrinogen and its derivatives, the amount of thrombin generated was even greater, about 130% larger than the amount which was generated in the presence of equal concentrations of only intact fibrinogen plus factor VIII. Addition of albumin instead of fibrinogen or its derivatives has a similar but significantly lower effect on thrombin generation. It appears, therefore, that both intact fibrinogen and its plasminolytic derivatives, singly or in combination, and to a lesser extent albumin, act as cofactors in the reaction which is regulated by factor VIII.