Clinical and biological evaluation in von Willebrand's disease of a von Willebrand factor concentrate with low factor VIII activity

Summary. This study was carried out to assess the clinical efficacy in von Willebrand's disease (vWD) of a new, very high purity (VHP), solvent/detergent (SD)-treated, vWF concentrate (VHP Human von Willebrand Factor Concentrate, Biotransfusion) characterized by a high specific ristocetin cofactor (vWF:RCo) activity and a low factor VIII (FVIII) coagulant activity (FVIII:C). Nine patients (four type I, one type IIA, one type IIB, one type IIC, one type III and one acquired type II) were infused on 13 occasions including a pharmacokinetic study. Satisfactory haemostasis was achieved in all cases, including the treatment of spontaneous haemorrhages and the prevention of bleeding following surgery. The bleeding time was corrected for 6–12 h in 6/9 patients and shortened in the others. Furthermore, it was shown that the plasma vWF multimeric pattern of types II and III patients was greatly improved. When measured in eight patients 1 h after infusion, the vWF: RCo recovery was 77·3 (± 10·7)% while the F VIII:C recovery was strikingly higher (876 ± 906%). This high recovery is likely related to the predominant ‘pseudo-synthesis’ of FVIII following the restoration of normal vWF levels. Maximum levels of FVIII: C occurred 6–12 h after the first infusion and normal levels of FVIII:C were maintained throughout the treatments with a dosage of 26–39 IU/kg vWF:RCo and only 0·2–5 IU/kg FVIII:C. The half-lives of the vWF-related parameters determined in a type III vWD patient were 20·6 h for vWF antigen, 17·8 h for vWF:RCo, 14 h for the high molecular weight multimers of vWF, 55·3 h for FVIII: Ag and 74 h for FVIII:C. In conclusion, it does not appear necessary that vWF concentrates intended for the treatment of vWD should contain FVIII in addition to vWF to be clinically effective in most patients.