Contact activation and factor VII after the use of an activated prothrombin complex concentrate (FEIBAR) in hemophiliacs with inhibitors

Administration of a brand of Activated Prothrombin Complex Concentrate (FEIBA) to Hemophiliacs with high-titre inhibitor to Factor VIII, induced a shortening of the Prothrombin Time and Thrombotest clotting time. This effect stems partly from the presence in the concentrate of high amounts of activated factor VII (α-VII_a) which indeed after the infusion, were detected in the plasma of Hemophiliacs. The attained levels of factor α-VII_a were shown to be proportional to the dose of concentrate administered. This form of activated factor VII was not generated as a result of activation of the contact activation mechanism, since after the infusion of the concentrate no changes were detected in the components of this system. The infused factor VII was indeed present in an activated form and this was further substantiated by the infusion of the concentrate in factor VII deficient patients. These observations suggest that factor α-VII_a is not generated $\text{in vivo}$ and thus is of exogenous origin. The clinical effect may well be due to the presence of this form of activated factor VII; in this context the alternative pathway involving factors IX and X should be implicated.