von Willebrand factor characterization of a severe dry-heat treated factor VIII concentrate, AHF (high purity).

ABSTRACT

Eight batches of a severe dry-heat treated (80 degrees C for 72 hours) Factor VIII concentrate manufactured by the Commonwealth Serum Laboratories (CSL Ltd.) were analysed for the following von Willebrand factor-related (vWf) activities ristocetin cofactor activity (vWfRCof), collagen binding activity (CBA), vWf antigen levels (vWfAg), vWf multimeric analysis and 2-stage FVIII clotting activity (VIIIC). The average potency per vial of vWfAg was 440 +/- 80 units, vWfRCof 500 +/- 60 units, CBA 350 +/- 50 units and VIIIC 242 +/- 36 International Units. Multimeric analysis indicated the presence of high molecular weight multimers and a triplet structure slightly different to normal plasma. Viral inactivation studies using a marker virus, Sindbis, demonstrated that the terminal severe dry- heating step reduced the viral load in the product by greater than 6 log10TCID50/ml. This CSL Ltd. FVIII concentrate may thus provide a safer, purer and more convenient source of vWf than cryoprecipitate. Clinical studies to establish product efficacy in patients with von Willebrand's disease are underway.