BIOCHEMICAL PROPERTIES OF COMMERCIAL, VIRUS-INACTIVATED FACTOR VIII CONCENTRATES

As all commercial factor VIII concentrates in current use have been subjected to some form of virus-inactivation, we wanted to compare their in vitro biochemical characteristics. Of the 10 concentrates studied, inactivation takes the form of dry heat treatment, varying from 60°C for 30 h to 72°C for 68 h, in six products (Octonativ, KabiVitrum; Hemofil T, Hyland; Factorate HP, Armour - heated two different ways; Monoclate, Armour; Nordiocto, Nordisk Gentofte). In the 4 remaining concentrates, inactivation is either by steam treatment (Kryobulin Tim 3, Immuno), heating at 60°C for 20 h as dry material slammed in heptane (Profilate, Alpha), wet-heating at 60°C for 10 h (Hemate, Behring), or by the New York Blood Center (solvent/detergent) method (OCTA-V. I., Octopharm). The variables studied were VIII:C by one-stage and chromogenic assay, and VI11 :Ag, vW:Ag, by electroimmunoassay, immunoradiometric assay (IRMA), crossed immunoelectrophoresis and SDS agarose gel electrophoresis followed by staining with radioactive antibody and fibrinogen. VIII :C activity values ranged from 20-53 IU/ml in all products but Monoclate (94 IU/ml). All products gave higher values of VIII:Ag than of VI11 :C, indicating partial inactivation of VIII :C during preparation; the ratios ranged from 1.2 to 1.3 for Kryobulin, Nordiocto, OCTA-V. I., and Hemofil T, and from 2 to 4 for the other products, being highest in Profilate and Monoclate. Specific activity was higher in Monoclate, Nordiocto, Hemate, OCTA-V. I. and Factorate HP (16.0, 7.4, 7.1, 4.8 and 3.3 IU/ml protein, respectively) than in the other products (1.3-2.3 IU/mg). All concentrates contained vW:Ag, and non-parallel dose-response curves indicated abnormality in the vWF molecule in all cases; and thus multimeric sizing failed to demonstrate the largest multimers of the vWF in any product. We conclude that although virus-inactivated F VIII concentrates are general ly comparable with regard to VIII :C content, they vary considerably in the degree of VIII :C inactivation during preparation, and in specific activity. No concentrate tested here contained native vWF. In vivo studies have shown VIII :C recovery and half-life to be comparable in heat-treated and non-heat-treated concentrates.