In vitro and in vivo Evaluation of a Factor VIII Concentrate Heat-Treated to Inactivate HTLV-III/LAV Viruses

Abstract

We report here the results of our evaluation of the effects of a dry heat treatment (96 h at 68 °C) to eliminate LAV/HTLV-III virus on factor Vili (FVIII) and von Willebrand factor (vWf) present in an intermediatepurity concentrate. This thermal inactivation appears to have little effect on FVIII. There is an acceptable loss (12.3 ± 3.6%; n = 25) in FVIII coagulant activity (FVIII: C) and a good in vivo performance in haemophilia A patients. A precise analysis of vWf indicates that whereas the vWf antigen and its ristocetin cofactor activity decrease during heating, there is an increase in potentially functional forms of vWf. Heat treatment induces an increase in high molecular weight forms of vWf and an enhancement in platelet adhesion to collagen. These changes probably explain the correcting effect on the bleeding time of the heated FVIII concentrate in patients with von Willebrand’s disease. Thus, this heat-treated concentrate appears to be equivalent to the untreated product in haemophilia A. with the additional benefit of being efficient for the treatment of von Willebrand’s disease.

Chromatographic Preparation of a Therapeutic Highly Purified von Willebrand Factor Concentrate from Human Cryoprecipitate

“…Correction of the platelet adhesion in the presence of purified collagen (nonfibrillar types I and III) was as sessed in rectangular perfusion chambers according to Sakariassen et al [21]. Samples were diluted to 0.75 U/ml vWF: Ag in a vWF-deficient plasma and the number of platelets fixed on the collagen was quantified [22]. Adhesion values were expressed as a percentage of the value found for a nondiluted normal plasma.…”