VWF and FVIII: the origins of a great friendship.

摘要

In this issue of Blood, van den Biggelaar and colleagues demonstrate the cotargeting of FVIII and VWF to secretory granules in the absence of a high-affinity interactions between VWF and FVIII, using recombinant VWF type 2N variants.In addition to mediating the adhesion of platelets to subendothelial tissue at the site of vascular injury, von Willebrand factor(VWF) also serves as the carrier protein for coagulation factor VIII (FVIII) in plasma. The initial point of physical association betweenthese 2 proteins remains unclear. When desmopressin (DDAVP) is administered to mild hemophilia or von Willebrand disease (VWD) patients, both FVIII and VWF are released into plasma. Presumably, VWF is released from endothelial cell Weibel-Palade bodies. While the liver is the major site of FVIII s)Tithesis, the cell within the liver producing FVIII has not been definitively identified. Recent publications suggest that FVIII may be present in selected endothelial populations including human lung microvascular endothelial cells and murine sinusoidal endothelial cells.1-2