The VWF monomer is heavily glycosylated with 20% by mass being composed of carbohydrate. The N-linked glycan structures of plasma VWF are complex type chains, with the majority being bi-antennary (78%) or tri-antennary (12%). The O-linked glycan structures of plasma VWF are short mucin-type carbohydrates and sialylated T antigen structures. Plasma VWF expresses terminal ABO(H) group antigens. In contrast, platelet VWF does not express A or B blood group antigens

[25], but it does express precursor H antigen (Fig. 3 [26]). Sialic acid expression on platelet VWF is significantly Dinaciclib price reduced, by >50% compared to plasma VWF. It is known that expression of terminal ABO blood group and sialic acid determinants on the N-linked glycans of VWF influence susceptibility to ADAMTS13 proteolysis [27, 28]. Recent work in the laboratory of O’Donnell et al. has demonstrated that due to differences in its glycosylation profile, platelet VWF is resistant to learn more proteolysis by ADAMTS13. Interestingly, other functional differences between platelet and plasma VWF have also been described. For example, GpIb binding is reduced five-fold for platelet VWF compared to plasma VWF [29]. In contrast, platelet VWF demonstrates significantly enhanced GpIIbIIIa binding and heparin binding compared to plasma VWF. Crossed bone marrow transplantation

studies in both pigs and mice have shown that platelet VWF is important in regulating normal haemostasis in vivo. In pigs with plasma VWF only, bleeding time was largely but not completely corrected and all pigs developed thrombosis in an arterial injury model. In contrast, selleck compound in pigs with platelet VWF only, the bleeding time was not corrected and none of the

pigs developed thrombosis [30]. A similar study in mice showed that platelet VWF plays a role in platelet adhesion to collagen under shear [31]. Human studies have demonstrated significant heterogeneity in platelet VWF:Ag and VWF:RCo among patients with type I VWD [32]. In addition, in vitro parallel plate flow studies suggest that platelet VWF may be important in regulating the adhesion of human platelets to collagen under shear stress [33]. Notwithstanding these data, the importance of platelet VWF in managing patients with VWD/pathological bleeding disorders remains poorly defined. This section focused on type 1 patients; type 1 is the most common form of the disease. Patients with type 1 VWD do not produce enough VWF, resulting in heavy bleeding during a bad injury or surgery. Although much is known about type 1 VWD, there are still areas where knowledge is lacking. A diagnosis of type 1 VWD is likely in patients with previous bleeding history (at least two bleeds at different sites) and reduced VWF:RCo in plasma (