ABO Blood Group as a Model for Platelet Glycan Modification in Arterial Thrombosis

Abstract

ABO blood groups have long been associated with cardiovascular disease, thrombosis and acute coronary syndromes. Many studies over the years have shown type O blood group to be associated with lower risk of cardiovascular disease compared to non-type O blood groups. However, the mechanisms underlying this association remain unclear. Although ABO blood group is associated with variations in concentrations of circulating von Willebrand Factor and other endothelial cell adhesion molecules, ABO antigens are also present on several platelet surface glycoproteins and glycosphingolipids. As we highlight in this platelet-centric review, these glycomic modifications may impact platelet function in arterial thrombosis. More broadly, improving our understanding of the role of platelet glycan modifications in acute coronary syndromes may inform future diagnostics and therapeutics for cardiovascular diseases.

Expresser phenotype determines ABO(H) blood group antigen loading on platelets and von Willebrand factor

“…In addition, accumulating data have demonstrated that ABO blood group also influences risk for cardiovascular disease 37 . Although the mechanisms through which ABO impacts vascular risk remain poorly understood, recent evidence suggests that ABO(H) expression on platelets influences platelet function 5 , 6 , 25 . Our data highlight that there is significant inter-individual heterogeneity in platelet A antigen expression, even amongst healthy group A 1 donors.…”

“…With respect to the relationship between ABO and cardiovascular risk, it is important to emphasize that ABO(H) blood group determinants are expressed on a variety of different glycoproteins and glycolipids on the platelet surface 5 . It remains unclear whether the HXP/LXP effects apply equally to ABO(H) loading on each of these different platelet glycoproteins.…”

“…Importantly however, ABO(H) antigens are also expressed on other human cells types including endothelial cells (EC) and epithelium 4 . In addition, ABO(H) determinants are expressed on platelets, where they have been identified on a variety of different glycoproteins known to play important roles in hemostasis (including GPIb, GpV, GpIIb/IIIa and PECAM-1) 5 . Recent studies have demonstrated that these ABO(H) glycans on the platelet membrane surface significantly influence normal platelet function 5 – 7 .…”

The Role of ABO Blood Type in Thrombosis Scoring Systems

“…[37][38][39] Beyond the association with levels of circulating VWF, recent investigations have been focused on the capacity of ABO blood group antigens to influence serum levels of several inflammatory cytokines (i.e., tumor necrosis factor-α, soluble intercellular adhesion molecule 1, E-selectin, P-selectin, and interleukin 6), whose higher concentrations have been associated with an increased risk of cardiovascular thrombotic events. [40][41][42][43] Finally, the observations of the association between the ABO locus and plasma lipoprotein concentrations 44 and between non-O blood types and increased circulating cholesterol levels 45,46 add another important contribution to the understanding of the pathogenic mechanisms underlying the correlation between ABO blood group and coronary heart disease susceptibility. All in all, these data document that the relation between the ABO blood group system and cardiovascular diseases is more complex than the simple modulation of hemostasis.…”

Cardiovascular disease, ABO locus, and markers of platelet functionality

“…It is for long known that ABO blood group antigens are present at the surface of platelets [2] and for nearly half a century, a link between ABO blood group antigens and cardiovascular disease was known [3]. ABO blood group is associated with many traits in addition to cardiovascular disease including platelet function parameters among healthy adults and patients with CAD [4,5].…”