title: Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis.
abstract: ABO blood group is an important determinant of plasma von Willebrand factor antigen (VWF:Ag) levels, with lower levels in group O. Previous reports have suggested that ABO(H) sugars affect the susceptibility of VWF to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 repeats-13) cleavage. To further test this hypothesis, we collected plasma from individuals with the rare Bombay blood group. VWF:Ag levels were significantly lower in Bombay patients (median, 0.69 IU/mL) than in groups AB, A, or B (P < .05) and lower than in group O individuals (median, 0.82 IU/mL). Susceptibility of purified VWF fractions to recombinant ADAMTS13 cleavage, assessed using VWF collagen-binding assay (VWF:CB), was increased in Bombays compared with either group O or AB. Increasing urea concentration (0.5 to 2 M) increased the cleavage rate for each blood group but eliminated the differences between groups. We conclude that reduction in the number of terminal sugars on N-linked glycan increases susceptibility of globular VWF to ADAMTS13 proteolysis and is associated with reduced plasma VWF:Ag and VWF:CB levels.
authors.affiliation: Haematology Dept, Imperial College London, 5th Floor, Commonwealth Building, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom. j.odonnell@imperial.ac.uk
authors.forename: James S
authors.initials: JS
authors.lastname: O'Donnell
authors.forename: Thomas A J
authors.initials: TA
authors.lastname: McKinnon
authors.forename: James T B
authors.initials: JT
authors.lastname: Crawley
authors.forename: David A
authors.initials: DA
authors.lastname: Lane
authors.forename: Michael A
authors.initials: MA
authors.lastname: Laffan
mesh_terms: D000017:ABO Blood-Group System / Q000737:chemistry*; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D002241:Carbohydrates / Q000737:chemistry; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D010641:Phenotype; D011134:Polysaccharides / Q000737:chemistry; D014508:Urea / Q000494:pharmacology; D014841:von Willebrand Factor / Q000032:analysis / Q000378:metabolism*
chemical_list: D000017:ABO Blood-Group System; D002241:Carbohydrates; D011134:Polysaccharides; D014841:von Willebrand Factor; D014508:Urea; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human