Upon vascular injury, subendothelial extracellular matrix components including collagen become exposed to the flowing blood (Bergmeier W & Hynes RO 2012). Circulating von Willebrand factor (VWF) binds to exposed vascular collagen (Colace TV & Diamond SL 2013). Upon binding to collagen, VWF becomes anchored to the damaged surface. Shear forces then induce conformational changes to mechanosensitive VWF causing the bound VWF to stretch and unfold (Li F et al., 2004; Schneider SW et al., 2007; Fu H et al., 2017). VWF unfolding leads to exposure of the A1 domain to allow binding to glycoprotein Ib α (GPIbα, encoded by GP1BA), a subunit of the platelet surface GPIb:IX:V complex (Dumas JJ et al. 2004; Ju L et al., 2013). This Reactome event describes von Willebrand disease (VWD)-associated missense mutations in the A1 domain of VWF, namely VWF S1358N, S1387I, S1394F and Q1402P, that compromise the clot formation. These VWF variants showed normal levels of expression, secretion, and multimerization but reduced binding to platelets (Larsen DM et al. 2013).