Utility of a high VWF: FVIII ratio in preventing FVIII accumulation: a study in VWF-deficient mice

Treatment of von Willebrand disease typically requires multiple infusions of von Willebrand factor (VWF)/factor VIII (FVIII) concentrate. Accumulation of FVIII is a clinical concern due to potential risk for thromboembolism. This study sought to determine whether VWF/FVIII concentrate of high VWF:FVIII ratio can prevent FVIII accumulation. VWF-deficient knockout mice received four 150 IU/kg VWF:ristocetin cofactor (RCo) infusions at 3-h intervals, with VWF/FVIII concentrates of a high (Haemate P/Humate-P) or low (Wilate) VWF:FVIII ratio. After each infusion, trough FVIII and VWF levels in plasma were determined. Separately, pharmacokinetic analysis was performed after single 250-IU/kg VWF:RCo infusions of each concentrate. Over the course of the four infusions, trough FVIII increased significantly in the group receiving Wilate (P