Initial synthesis of von Willebrand factor (vWf) by cultured human endothelial cells proceeds by formation of a dimer of pro-vWf subunits. These subunits are found only within the cell and have an apparent molecular weight of 240,000-260,000, as measured by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels. Posttranslational modifications, including proteolytic cleavage, glycosylati...

Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human populat...

Platelet adhesion to fibrin at high shear rates depends on both the glycoprotein (GP) IIb:IIIa complex and a secondary interaction between GPIb and von Willebrand factor (vWF). This alternative link between platelets and vWF in promoting platelet adhesion to fibrin has been examined in flowing whole blood with a rectangular perfusion chamber. Optimal adhesion required both platelets and vWF, as...

OBJECTIVE Endotoxin (lipopolysaccharide [LPS]) enhances microvascular thrombosis in mouse cremaster venules. Because von Willebrand factor (vWF) and P-selectin are suggested to mediate LPS-induced platelet-microvessel interactions, we determined whether vWF and P-selectin contribute to microvascular thrombosis in endotoxemia. METHODS AND RESULTS A light/dye-induced thrombosis model was used i...

The function of von Willebrand factor (VWF), a huge multimeric protein and a key factor in platelet dependent primary haemostasis, is regulated by its specific protease ADAMTS13. The ADAMTS13 dependent degradation of VWF to its proteolytic fragments can be visualized as a characteristic so-called triplet structure of individual VWF oligomers by multimer analysis. Lack of VWF high molecular weig...

The respective role of plasmatic and endothelial extracellular matrix (ECM)-associated von Willebrand factor (vWF) in platelet adhesion was investigated at a high shear rate using a parallel-plate perfusion chamber. Incubation of the endothelial ECM with a monoclonal antibody (MoAb) to vWF, which specifically blocks vWF binding to platelet GP Ib (MoAb 322), inhibited 45% of platelet adhesion. C...

We examined the role of N-linked glycan structures of VWF on its interaction with ADAMTS13. PNGase F digestion followed by lectin analysis demonstrated that more than 90% of VWF N-linked glycan chains could be removed from the molecule (PNG-VWF) without disruption of its multimeric structure or its ability to bind to collagen. PNG-VWF had an approximately 4-fold increased affinity for ADAMTS13 ...

von Willebrand disease (VWD) is a genetic bleeding disease due to a defect of von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels <50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants...

Uremia is associated with a bleeding diathesis. We investigated platelet adhesion as a cause for the impaired primary hemostasis and the role of von Willebrand factor (vWF) in this process in uremic patients. Perfusions with blood with standardized hematocrit, platelet count, and free Ca2+ ions were performed over inverted and deendothelialized artery segments from human umbilical cords in a mo...

The binding of factor VIII to von Willebrand factor (vWF) is essential for the protection of factor VIII against proteolytic degradation in plasma. We have characterized the binding kinetics of human factor VIII with vWF using a centrifugation binding assay. Purified or plasma vWF was immobilized with a monoclonal antibody (MoAb RU1) covalently linked to Sepharose (Pharmacia LKB Biotechnology, ...