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-1...

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Bibliographic Details
Published in:Blood 2005-09, Vol.106 (6), p.1988-1991
Main Authors: O'Donnell, James S., McKinnon, Thomas A.J., Crawley, James T.B., Lane, David A., Laffan, Michael A.
Format: Article
Language:English
Subjects:
ABO Blood-Group System - chemistry
ADAM Proteins
ADAMTS13 Protein
Biological and medical sciences
Blood coagulation. Blood cells
Carbohydrates - chemistry
Fundamental and applied biological sciences. Psychology
General aspects, investigation methods, hemostasis, fibrinolysis
Humans
Metalloendopeptidases - metabolism
Molecular and cellular biology
Phenotype
Polysaccharides - chemistry
Urea - pharmacology
von Willebrand Factor - analysis
von Willebrand Factor - metabolism
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-02-0792