Relationship between ABO blood group and von Willebrand factor levels: from biology to clinical implications

In this review, the most recent advances in our understanding of the mechanisms by which ABO blood group determines plasma VWF levels and their clinical impact will be discussed.Von Willebrand factor (VWF) is a large adhesive glycoprotein synthesized by endothelial cells and megakaryocytes that circulates in the plasma as a series of heterogeneous multimers [1-3].VWF has two major functions in hemostasis. First, it is essential for platelet-subendothelium adhesion and platelet-to-platelet interactions as well as platelet aggregation in vessels in which rapid blood flow results in elevated shear stress. Second, VWF is the specific carrier of factor VIII (FVIII) in plasma and protects it from proteolytic degradation, prolonging its half-life in circulation and efficiently localizing it at the site of vascular injury [4].While a deficiency of VWF is responsible for a hemorrhagic diathesis (von Willebrand disease, VWD) [5], there are increasing evidences that elevated VWF levels represent an important thrombotic risk factor [6,7].Besides the VWF gene (12p12), it is well established that other gene loci exert major quantitative effects on VWF plasma levels. The most important of these loci has been shown to be the ABO blood group locus on chromosome 9q34 [8,9].The antigens of the ABO system (A, B, and H determinants, respectively) consist of complex carbohydrate molecules. The A and B alleles encode slightly different glycosyltransferases that add N-acetylgalactosamine and D-galactose, respectively, to a common precursor side chain, the H determinant, converting it into A- or B-antigens. The O alleles do not encode a functional enzyme and consequently OO carriers, who lack such transferase enzymes, continue to express the basic, unmodified, H-antigen with a fucose moiety attached to precursor oligosaccharide chains[10].The nature of the interaction between ABO blood group antigens and plasma VWF levels along with its clinical implication will be discussed in this review.