Activated factor VII: presence in factor IX concentrates and persistence in the circulation after infusion.

Factor IX concentrates were evaluated for their factor VII content and for the presence of activated factor VII through use of a coupled amidolytic assay insensitive to activated factor VII and a clotting assay sensitive to activated factor VII. The factor VII content of the concentrates studied (except for one concentrate purposely produced to exclude factor VII) varied between 33 and 621 U/vial. All concentrates contained activated factor VII. as indicated by ratios of factor VII clotting activity to factor VII amidolytic activity, of from 1.6 to 21.5. Higher ratios were found in two brands of activated concentrates than in nonactivated concentrates. In patients infused with factor IX concentrates, plasma factor VII activity rose strikingly in the clotting assay but not in the amidolytic assay. Thus, the elevated factor VII levels by the clotting assay after infusion of factor IX concentrates stem from circulating activated factor VII. A mean intravascular half-disappearance time of 144 mm was found for activated factor VII. Its persistence in the circulation makes it important to evaluate the possible role of activated factor VII in the thrombogenicity of factor IX concentrates and in their reported effectiveness in treating bleeding in hemophilia A patients with inhibitors.