High concentrations of coagulation factor VIII and thrombosis: Is the factor VIII-binding domain of von Willebrand factor implicated?

The possibility that high factor VIII (FVIII) levels in thrombosis patients is principally explained by a gain of function in the FVIII-binding domain of von Willebrand factor (VWF), arising from amino acid substitution(s) or polymorphism(s), was investigated. Exons 18-24 of the VWF gene were sequenced in 13 thrombosis patients with high FVIII (> 1.50 IU/ml). No novel mutations were found. Four known polymorphisms were detected: G2615A and C2635T (Ex18), G2805A (Ex20) and G3130A (Ex22). Their frequencies showed no significant differences in a thrombosis vs. control cohort. The data suggest that amino acid substitutions/polymorphisms in the VWF-FVIII-binding domain are not the principal explanation for high FVIII in thrombosis patients.