Pharmacokinetics and hemostatic effect of different factor VIII/von Willebrand factor concentrates in von Willebrand's disease type III.

Four different plasma-derived concentrates composed of coagulation factor VIII (FVIII) and von Willebrand factor (vWF) of varying quality (Hemate-P, Behring; Profilate, Alpha; and F VIII-VHP-vWF, C.R.T.S Lille), or almost purified vWF (Facteur Willebrand, C.R.T.S Lille) and one recombinant F VIII concentrate (Recombinate, Baxter) were given, in doses of 30-60 IU VIII: C/kg or 70-110 IU RCof/kg, to five patients with von Willebrand's disease type III, in order to evaluate the role of the vWF in factor F VIII concentrates. All plasma concentrates except Profilate had a multimeric vWF pattern almost similar to that of normal plasma. Bleeding time (b.t.), VIII: C, vWF:Ag, ristocetin cofactor activity, and multimeric pattern of the plasma-vWF were followed for 72 h. Both Duke b.t. and the multimeric pattern in plasma normalized after infusion of Hemate-P, F VIII-VHP-vWF, and Facteur Willebrand and, to a lesser extent, after Profilate. As expected, in response to Recombinate there was no effect on primary hemostasis, and the half-life of F VIII procoagulant activity (VIII: C) was very short. Normalization of the vWF is important not only for improving the primary hemostasis, but also for maintaining the plasma F VIII concentration on a high level, both by reducing the elimination rate of infused F VIII and via a secondary release of endogenous F VIII. If a prompt hemostatic effect is required, we recommend a concentrate containing both F VIII and all vWF multimers, but for prophylactic treatment, pure vWF may be used.