Factor VIII Preparation (RCG-5) with Intermediate Purity and Potency

Abstract

In order to avoid the spread of AIDS among hemophiliacs and to reduce the dependance of the plasma source on the foreign countries, a new factor VIII concentrate with intermediate purity and potency (RCG-5) was developed using fresh plasma from healthy volunteer donors after several screening tests.
RCG-5 was prepared from a small pool of cryoprecipitate (2∼10 donors) and subsequent defibrination with heat treatment at 54°C for 5 min in the presence of glycine and NaCl. In spite of the heat treatment, about 90% of the factor VIII procoagulant activity (F. VIII: C) and ristocetin cofacter activity (RCof) could be retained, whereas more than 90% of the fibrinogen was removed from the cryoprecipitate. None of new antigenicity was developed by heat treatment. During the defibrination process, some marker viruses such as Sindbis and VSV as well as HIV and HBV could be inactivated and/or removed.
RCG-5 was found to contain 19.5 u/ml of F. VIII: C on the average, 28.0 u/ml of F. VIII antigen (F. VIII: Ag), 29.0 u/ml of RCof, 30.7 u/ml of von Willebrand factor antigen (vWF: Ag) and 10.4 mg/ml (0.5 mg/unit of F. VIII: C) of fibrinogen. The ratio of F. VIII: Ag to F. VIII: C and vWF: Ag to RCof in RCG-5 was 1.4 and 1.1, respectively. They were very close to cryoprecipitate. These suggest that the inactivation of biological activities of F. VIII and vWF little occurred during production procedure. RCG-5 has a remarkable correcting effect on the defective ristocetin-induced platelet aggregation in the patient with von Willebrand disease (vWD). It also showed large, intermediate and small multimers of vWF just similar to normal plasma or cryoprecipitate.
From these results RCG-5 is expected to be a new useful preparation for the patients with hemophilia A as well as vWD.