Platelets and von Willebrand factor (VWF) are recognized as important mediators of thrombosis at high shear rates, but their relative contributions are unclear. We employ a stenotic microfluidic test system to induce thrombus formation to occlusion on collagen at pathologic shear rates of 3500-6000 s-1. To obtain blood analogs with reduced platelet and VWF concentrations, human whole blood was ...

Ultralarge von Willebrand factor (ULVWF) multimers are thought to play a central role in pathogenesis of the disease thrombotic thrombocytopenic purpura (TTP); however, experimental evidence in support of this hypothesis has been difficult to establish. Therefore, to examine directly the requirement for VWF in TTP pathogenesis, we generated ADAMTS13-deficient mice on a TTPsusceptible genetic ba...

Weibel-Palade bodies (WPBs) are the endothelial storage organelles that are formed upon von Willebrand factor (VWF) expression. Apart from VWF, WPBs contain a variety of hemostatic and inflammatory proteins. Some of these are thought to be targeted to WPBs by directly interacting with VWF in the secretory pathway. Previous studies have demonstrated that coexpression of factor VIII (FVIII) with ...

Lung adenocarcinoma (LAC) is the leading cause of cancer-related death worldwide. Aberrant expression of genes expressed preferentially in the lung tumor vasculature may yield clues for prognosis and treatment. Von Willebrand factor (vWF) is a large multifunctional glycoprotein with a well-known function in hemostasis. However, vWF has been reported to exert an anti-tumor effect, independent of...

Type 1 VWD is the mild to moderate reduction of VWF levels. This study examined the mechanisms underlying 2 common type 1 VWD mutations, the severe R1205H and more moderate Y1584C. In vitro biosynthesis was reduced for both mutations in human and mouse VWF, with the effect being more severe in R1205H. VWF knockout mice received hydrodynamic injections of mouse Vwf cDNA. Lower VWF antigen levels...

BACKGROUND To avoid pathological platelet aggregation by von Willebrand factor (VWF), VWF multimers are regulated in size and reactivity for adhesion by ADAMTS13-mediated proteolysis in a shear flow dependent manner. OBJECTIVE AND METHODS We examined whether tensile stress in VWF under shear flow activates the VWF A2 domain for cleavage by ADAMTS13 using molecular dynamics simulations. We gen...

The vascular endothelium is involved in the production of many important substances which are involved in a cardiovascular pathophysiology. One such substance which is synthesised by, and stored in, endothelial cells is von Willebrand factor (vWf). When released, vWf appears to mediate platelet aggregation and adhesion. Numerous clinical and experimental reports suggest that high vWf levels ref...

In patients with thrombotic thrombocytopenic purpura (TTP), excessive intravascular platelet aggregation has been associated with appearance in plasma of unusually large von Willebrand factor (vWF) multimers. These extremely adhesive vWF multimers may arise due to deficiency of a "depolymerase" cleaving vWF to smaller molecular forms, either by reducing the interdimeric disulfide bridges or by ...

von Willebrand disease (VWD) is a common bleeding disorder caused by defective or low levels of von Willebrand factor (VWF). Although most cases of VWD are caused by genetic mutations, some are acquired due to various disease states. In managing VWD, the aim is to normalize plasma levels of both VWF and factor VIII (FVIII), as this aids in hemostasis. Desmopressin usually corrects VWF level in ...

Abstract — Von Willebrand factor (vWF), the key component of hemostasis, is synthesized in endothelial cells and megakaryocytes released into blood as high molecular weight multimeric glycoproteins weighing up to 20 million Daltons. Blood plasma metalloprotease ADAMTS13 cleaves ultra-large vWF multimers smaller oligomeric molecules. The molecules attach sites damage at surface arterioles capill...