von Willebrand factor (VWF) is an essential component of hemostasis and has been implicated in thrombosis. Multimer size and the amount of circulating VWF are known to impact hemostatic function. We associated 78 VWF single nucleotide polymorphisms (SNPs) and haplotypes constructed from those SNPs with VWF antigen level in 7856 subjects of European descent. Among the nongenomic factors, age and...

Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in αgranules of platelets and is enriched in hyperactive ‘ultra-large’ VWF multimers. To elucidate the specific contribution of platelet VWF in hemostasis and thrombosis we performed crossed bone marrow transplantations between C57BL/6J and Vwf mi...

Soluble von Willebrand factor (VWF) has a low affinity for platelet glycoprotein (GP) Ibalpha and needs immobilization and/or high shear stress to enable binding of its A1 domain to the receptor. The previously described anti-VWF monoclonal antibody 1C1E7 enhances VWF/GPIbalpha binding and recognizes an epitope in the amino acids 764-1035 region in the N-terminal D'D3 domains. In this study we ...

Von Willebrand factor (VWF) and factor VIII (FVIII) circulate in a tight noncovalent complex. At present, the cells that contribute to the removal of FVIII and VWF are of unknown identity. Here, we analyzed spleen and liver tissue sections of VWF-deficient mice infused with recombinant VWF or recombinant FVIII. This analysis revealed that both proteins were targeted to cells of macrophage origi...

We have recently shown that von Willebrand factor (vWF) binds to endothelial and fibroblastic extracellular matrixes (ECM) in a dose-dependent, specific, and saturable way. To localize the domain on the vWF subunit responsible for this interaction, purified proteolytic fragments of vWF were compared for their ability to inhibit 125I-vWF binding to ECM. A tryptic dimeric fragment of 116 kD (T116...

While studying patient plasma containing an unusual pattern of von Willebrand factor (VWF) multimers, we discovered a previously unreported phenomenon: heavy predominance of dimeric VWF. Genomic analysis revealed a new congenital mutation (Tyr87Ser) that altered the final stages of VWF biosynthesis. This mutation in the propeptide (VWFpp) resulted in synthesis of dimeric VWF with an almost comp...

BACKGROUND Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule bio...

Endothelial cells secrete prothrombotic ultralarge von Willebrand factor (VWF) multimers, and the metalloprotease ADAMTS13 cleaves them into smaller, less dangerous multimers. This reaction is stimulated by tensile force applied to the VWF substrate, which may occur on cell surfaces or in the circulating blood. The cleavage of soluble VWF by ADAMTS13 was accelerated dramatically by a combinatio...

A collagen-binding domain of von Willebrand factor (vWF) has been identified in the central part of the molecule by comparing the binding properties of vWF and Staphylococcus aureus V-8 protease-generated vWF fragments with collagen. The binding of purified human vWF to human type Ill collagen was found to be specific. At saturation. 38 to 50.2 zg of vWF bound per milligram of collagen. Scatcha...

The cysteine allele of the amino acid polymorphism (AAP) Y/C1584 in the A2 domain of von Willebrand factor (VWF) has been shown to correlate with enhanced VWF proteolysis by ADAMTS13. The frequencies and effect on VWF proteolysis of six reported AAP in VWF domains A1 and A2 were investigated. Only two AAP were variant: 4414 G/C (D/H1472) (allele frequency 0.86/0.14) and 4693 G/T (V/L1565) (alle...