HIGH-PURITY FACTOR-IX CONCENTRATES FOR TREATMENT OF HEMOPHILIA-B - RELATIVE PURITY AND THROMBOGENIC POTENTIAL

Constituents other than factor UC have been implicated as etiologic ag ents for thrombotic complications in patients receiving prothrombin co mplex concentrates (PCCs). In vitro studies, in vivo animal models, an d clinical evaluations in patients with hemophilia B indicate that hig h-purity factor IX concentrates contain significantly fewer potentiall y thrombogenic contaminants than PCCs. A recent in vitro study from ou r laboratory used highly sensitive assays to analyze the relative puri ty of these newer products. The following products were studied using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) a nalysis and immunoblotting: Aimafix, AlphaNine-SD, Factor IX VHP, Immu nine, Mononine, Nanotiv, and 9MC (now known as Replinine). The mean sp ecific activity of the high-purity factor M products ranged from 68 IU factor IX/mg (Aimafix) to 246 IU factor IX/mg (Mononine). SDS-PAGE an alysis under reducing and nonreducing conditions showed that Mononine had the fewest contaminating bands. The immunoblot to detect factor IX showed a dominant factor IX band for all products, visible Light chai n of factor IX for all products except Aimafix, and another contaminat ing band visible at 49,500 daltons for all products except 9MC. High m olecular weight contaminants were apparent for some products. Factor V IIa was detected in some lots of Immunine, Nanotiv and 9MC. Factor X a nd prothrombin contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immu nine, Nanotiv and 9MC. Thus, Mononine, Nanotiv and 9MC demonstrated th e highest purity but no product was totally free of contaminants.