title: High concentrations of coagulation factor VIII and thrombosis: Is the factor VIII-binding domain of von Willebrand factor implicated?
abstract: 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.
authors.affiliation: Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, UK. bowendj1@cf.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Bowen
authors.forename: R M
authors.initials: RM
authors.lastname: MacLean
authors.forename: S
authors.initials: S
authors.lastname: Pellard
authors.forename: P W
authors.initials: PW
authors.lastname: Collins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D020180:Heteroduplex Analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D014841:von Willebrand Factor; C028254:von Willebrand factor receptor; D005169:Factor VIII