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

Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis
E RaquetG Dickneite

Abstract

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 < 0.001), but not Haemate P/Humate P (P = 0.058). After the first infusion, mean trough FVIII level in the Wilate group (31.7 IU/dl) was greater by 82% (P = 0.017) than that in the Haemate P/Humate P group (17.4 IU/dl). After the final infusion, mean trough FVIII of animals receiving Wilate (55.1 IU/dl) continued to exceed that of Haemate P/Humate P recipients (30.2 IU/dl) significantly (P < 0.001). Tr...Continue Reading

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