Efficacy and safety of a factor VIII-von Willebrand factor concentrate 8Y: Stability, bacteriological safety, pharmacokinetic analysis and clinical experience

The present study was undertaken to evaluate stability, pharmacokinetic profile and efficacy of continuous infusion of 8Y in patients with different types of von Willebrand disease (vWD). Following reconstitution, 8Y levels of von Willebrand factor ristocetin cofactor (vWF:Rco), vWF antigen and factor VIII coagulant activity (FVIII:C) decreased to about 80% of the baseline levels; addition of low molecular weight heparin decreased the level of FVIII:C even further. Reconstituted 8Y was found to be sterile for up to 6 days postreconstitution. Ten vWD patients (four with type 2A, three with type 3, two with type 1 and one with 2N) underwent pharmacokinetic analysis. The recovery of vWF: RCo was significantly lower in patients with type 3 vWD (1.4 ± 0.05% U^-1 kg^-1) compared with that of the patients with types 1 (2.3 ± 0.52% U^-1 kg^-1) or 2A (2.0 ± 0.06% U^-1 kg^-1) vWD (P = 0.015). Type 3 vWD patients exhibited significantly higher vWF:RCo clearance (5.1 ± 1.1 mL kg^-1 h^-1) compared with that of patients with type 2A (2.8 ± 0.7 mL kg^-1 h^-1) and type 1 (2.6 ± 1.0 mL kg^-1 h^-1) vWD (P = 0.028). Accordingly, terminal half-life was lower in patients with type 3 vWD (8.0 ± 0.6 h^-1) compared with type 2A (12.7 ± 5.9 h^-1) or type 1 (14 ± 1.2 h^-1) vWD patients. Multimeric pattern of vWF from patients' plasma was similar to that of 8Y. In two patients treated with 8Y by continuous infusion for prevention or treatment of bleeding haemostasis was achieved. Thus, 8Y is suitable and haemostatically effective for continuous infusion treatment in patients with vWD.