Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis.
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.
O'Donnell
James S
JS
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
McKinnon
Thomas A J
TA
Crawley
James T B
JT
Lane
David A
DA
Laffan
Michael A
MA
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*
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