title: Clinical and biological evaluation in von Willebrand's disease of a von Willebrand factor concentrate with low factor VIII activity.
abstract: 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.
authors.affiliation: Laboratoire d'Hématologie B, Centre Hospitalier Régional et Universitaire, Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Goudemand
authors.forename: C
authors.initials: C
authors.lastname: Mazurier
authors.forename: A
authors.initials: A
authors.lastname: Marey
authors.forename: C
authors.initials: C
authors.lastname: Caron
authors.forename: B
authors.initials: B
authors.lastname: Coupez
authors.forename: P
authors.initials: P
authors.lastname: Mizon
authors.forename: M
authors.initials: M
authors.lastname: Goudemand
mesh_terms: D000328:Adult; D000368:Aged; D005169:Factor VIII / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D014842:von Willebrand Diseases / Q000097:blood / Q000188:drug therapy*; D014841:von Willebrand Factor / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D014841:von Willebrand Factor; D005169:Factor VIII