A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor

Abstract

IntroductionPlatelet plug formation at the site of vascular injury is initiated by von Willebrand factor (VWF) interacting with the subendothelial matrix, followed by its binding to platelet glycoprotein (GP) Ib 1,2 and subsequent platelet activation and aggregation. VWF is synthesized by endothelial cells and megakaryocytes, 3,4 and one of its main particular features is a polymer structure ranging in size from 500 000 to more than 20 million Dalton, 5 the largest forms being hemostatically the most efficient. 6 A broad range of values characterizes plasma VWF levels, which average around 10 g/mL. Acquired and inherited factors both modulate plasma VWF levels, and twin studies have demonstrated that 66% of all variations in plasma VWF are genetically determined, while 30% of them depend on ABO blood group, 7 O blood group individuals having plasma VWF levels 25% lower than non-O subjects. 8 ABO group genotyping shows that O 1 O 1 subjects have the lowest VWF levels, and non-O group individuals heterozygous for the O 1 allele have significantly lower VWF levels than AA, AB, or BB subjects. 9,10 Glycosylation accounts for 19% of VWF by weight, and ABO determinants identified on the N-linked oligosaccharide chains are part of this glycosylation process. 11,12 ABO groups are added to the N-linked glycan chains of VWF in the post-Golgi compartment of endothelial cells before VWF secretion, albeit with the variable contribution of the endothelial cells from different vascular beds. 13 The carbohydrate moiety plays an important part in VWF polymerization and function, 14 and also affects the liver-mediated clearance of VWF. In animal models, the removal of sialic acid has been shown to induce an increase in VWF clearance, 15 and the half-life of VWF is halved in mice characterized by an aberrantly glycosylated VWF (due to the absence of the enzyme ST3Gal-IV). 16 Moreover, recombinant VWF, lacking in carbohydrate, is cleared from the circulation faster than its glycosylated counterpart, 16 and posttranslational changes in VWF induced by Galgt2, aberrantly expressed in endothelial cells, lead to a 20-fold increase in VWF clearance. 17 ABO group determinants may also regulate the susceptibility of VWF to the proteolytic action of ADAMTS13, proteolysis being faster in the case of the O blood group. 18 A different susceptibility to cleavage by ADAMTS13 may thus be one of the ways in which ABO group affects VWF removal from the circulation and consequent VWF levels.Although the mechanisms behind ABO blood group and VWF levels have yet to be fully clarified, it has been clearly demonstrated that the effects are mediated by the ABO antigen structures on the N-linked oligosaccharide chains of circulating VWF, and particularly by H antigen expression. 19 Understanding these mechanisms is of clinical relevance: non-O individuals have been shown to carry a significantly greater risk of venous thromboembolism, ischemic heart disease, and peripheral vascular disease, 21-23 while the O blood group is much more common in von Willebra...

Prognostic value of preoperative von Willebrand factor plasma levels in patients with Glioblastoma

“…Blood group was known in 51 patients (64%), being O in 34 (43%). Since VWF tends to be lower in individuals with O blood groups 20, we analyzed separately VWF levels in both blood groups, and in spite of everything in GBM patients with O group, the levels were still higher respect to MNGs (median 250 IU/dL, IQR 175.50–355 vs. 164 IU/dL, IQR 121–200). Moreover, the same proportion of O/non‐O blood group was found analyzing separately patients with MNG and those with GBMs.…”

“…For this reason, we performed a subanalysis in a group of age‐matched GBMs and MNGs, confirming that VWF levels were significantly related with survival irrespective of age. For the same reason, since VWF tend to be higher in individuals with non‐O blood groups 20, we checked that the distribution of ABO blood groups was similar between patients with GBMs and those with MNGs in order to rule out that the increased VWF levels were not attributable to a skewed blood group distribution. Indeed, as reported by Akin, differences in VWF levels between O and non‐O groups are more reliable for VWF values lower than 50 IU/dL, while in our patients, VWF levels are always higher, so as not to show significant differences between ABO groups 29.…”

Association between Endothelial Progenitor Cells and von Willebrand Factor in Astrocytic Glioma

“…al;2008). In current study, the data showed that the plasma vWF/FVIII associated with the brain tumor EPCs and not with the adjacent normal brain EPCs in the astrocytic glioma.…”

“…The vWF is a mediator that involved in adhesion of platelets to the collagen and hemostatic plug formation (Spiel et. al;2008). The vWF not only function in the platelet adhesion to the vessel wall but also enhance the platelet to platelet interaction under high shear-stress conditions (Rumbaut et.…”

“…The release of vWF from endothelial cell storage sites can be stimulated by vasopressin analog (Gallinaro et. al;2008). The vWF-glycoprotein is important for normal hemostasis that involved in inflammation and to regulate angiogenesis (Starke et.…”