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Pharmacokinetics of von Willebrand factor and factor VIII coagulant activity in patients with von Willebrand disease type 3 and type 2.
Nine patients with von Willebrand disease type 3, six with type 2B, one with type 2A, and one patient with type 1/2N were infused with one dose of approximately 50 or 100 IU ristocetin cofactor activity (RCoF) per kg body weight of von Willebrand factor (vWF) (Human), a product with a very low content of factor VIII (FVIII). Blood samples were collected over 96 h. The data for RCoF and vWF antigen (vWF:Ag) were fitted to a 1-compartment model decay. The data for FVIII:C were fitted to a model with a linear time 'synthesis' term and a 1-compartment decay. Results in von Willebrand disease type 3 patients (nine patients; 10 infusions) indicated a volume of distribution of 39.9 and 39.8 mL kg-1 for RCoF and vWF:Ag, respectively. The FVIII:C rate of synthesis was 6.4 U dL-1 h-1 (range: 4.4-8.8). The decay rates for FVIII:C, RCoF, and vWF:Ag were 0.041 (h-1) [t1/2: 16.9 h]; 0.061 (h-1) [t1/2: 11.3 h] and 0.006 (h-1) [t1/2: 12.4 h], respectively. In patients with von Willebrand disease type 2 (n = 8) the RCoF mean volume of distribution was 46 mL kg-1. The factor VIIIC mean rate of synthesis was 5.5 U dL-1 h-1 and the decay rate 0.043 (h-1) [t1/2: 16.1 h]. The rate of decay for RCoF and vWF:Ag were 0.050 (h-1) [t1/2: 13.9 h] and 0.044 (h-1) [t1/2: 15.7 h], respectively.
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