The relationship between ABO blood group, von Willebrand factor, and primary hemostasis

Abstract

Numerous studies have reported significant associations between ABO blood group and risk for cardiovascular disease. These studies have consistently demonstrated that thrombotic risk is significantly reduced in blood group O individuals. Nevertheless, the biological mechanisms through which ABO influences hemostasis have remained poorly understood. Exciting recent data have provided novel insights into how these ABO effects are modulated, and highlighted that ABO group significantly influences platelet plug formation at sites of vascular injury (primary hemostasis). In particular, ABO affects multiple aspects of von Willebrand factor (VWF) biology. In keeping with their reduced thrombotic risk, plasma VWF levels are approximately 25% lower in normal group O compared to non-O individuals. In addition, blood group O VWF demonstrates enhanced susceptibility to ADAMTS13 proteolysis. Finally, preliminary findings suggest that the ability of group O VWF to interact with platelets may also be reduced. Although the molecular mechanisms underlying these ABO effects on VWF have not been fully elucidated, it seems likely that they are mediated in large part by ABO(H) carbohydrate structures carried on both the N- and O-linked glycans of VWF. Interestingly, ABO(H) determinants are also expressed on a number of different platelet surface glycoprotein receptors. Recent studies support the hypothesis that ABO group not only exerts major quantitative and qualitative effects on VWF, but also may affect specific aspects of platelet function. Given the huge morbidity and mortality associated with thrombotic disorders, defining the mechanisms underlying these ABO effects is not only of scientific interest, but also of direct clinical importance.

Blood group A Secretors are associated with a higher risk of COVID-19 cardiovascular disease complications

“…The association of blood group A with cardiac disease is well documented and is linked to VWF (reviewed by 32 ). Our data are the first to specifically link the severity of disease in COVID-19 patients to homozygous group A individuals who are also secretors.…”

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

“…29 Many of these mutations are clustered around the D3 and A1 domains, but variants affecting other VWF domains have also been reported (e.g., S2179F in the D4 domain and C2671Y in the CK domain). 29 VWF is heavily glycosylated 30 and alterations in VWF glycan structures have also been associated with triggering enhanced clearance in vivo. [30][31][32][33][34] Although several VWF clearance receptors have been described, 29,[35][36][37][38][39] the molecular mechanisms through which single amino acid substitutions and glycan changes lead to pathological enhanced VWF clearance in vivo remains poorly understood.…”

“…29 VWF is heavily glycosylated 30 and alterations in VWF glycan structures have also been associated with triggering enhanced clearance in vivo. [30][31][32][33][34] Although several VWF clearance receptors have been described, 29,[35][36][37][38][39] the molecular mechanisms through which single amino acid substitutions and glycan changes lead to pathological enhanced VWF clearance in vivo remains poorly understood. 29,40 Nevertheless, cumulatively these findings have led to the suggestion that type 1 VWD patients with enhanced clearance should be considered as a distinct type 1C (1-Clearance) subgroup.…”

The Influential Incidence and Prevalence of Angiohemophilia

“…The disorder is a key feature in most cases. The extreme type 3 disorder, by comparison, demonstrates a recessive ancestry trend and parents typically do not have clinical symptoms [7].…”