Studies of factor IX concentrate therapy in hemophilia.

The effects of factor IX concentrate therapy on hemostasis in hemophilia patients were studied by means of the radiometric factor IXa assay, the coupled amidolytic assay for factor VIIa, and coagulant assays for factors II, IX, and X, and antithrombin III. Both activated and unactivated concentrates contained factors VIIa and IXa, with the highest levels in the activated concentrates. Factors VIIa and IXa were detected in patient plasma after infusion of unactivated concentrates. Increases of 3-5--fold in factors II and X were also found. Major decreases in antithrombin III activity, but not antigen, were found after unactivated concentrate therapy. This functional decrease may be due to the presence of inactive antithrombin III complexes, since a decreased mobility of antithrombin III antigen by crossed immunoelectrophoresis was found. These studies support the possible importance of factors IXa and VIIa as therapeutic agents and suggest that a transient functional deficiency in antithrombin III may be involved in the thrombotic potential of the concentrates.