Dec 29, 2009 · The interaction of factor VIII (FVIII) with von Willebrand Factor (VWF) is of direct clinical significance in the diagnosis and treatment of patients with haemophilia A and von Willebrand disease (VWD). A normal haemostatic response to vascular injury requires both …

Nov 3, 2023 · Here, we addressed the role of von Willebrand factor (VWF) as a modulator of anti-FVIII antibody effector functions and the FVIII-specific recall response in an HA mouse model. Analytical ultracentrifugation was used to demonstrate formation of FVIII-containing immune complexes (FVIII-ICs).

Factor VIIII (FVIII) and von Willebrand factor (VWF) are two distinct but related glycoproteins that circulate in plasma as a tightly bound complex (FVIII/VWF). Their deficiencies or structural defects are responsible for the most common inherited bleeding disorders, namely …

Aug 20, 2015 · The high-affinity, noncovalent association of factor VIII (FVIII) with von Willebrand factor (VWF) in the circulation protects FVIII from otherwise rapid clearance. 1,2 Quantitative insufficiency of VWF, characteristic of type 1 and type 3 von Willebrand disease (VWD), as well as impaired FVIII binding by VWF, observed in type 2N VWD, result in ...

Factor VIII (FVIII) and von Willebrand factor (vWF) can be defined as the factors that correct the plasmatic defect in hemophilia A and von Willebrand's disease, respectively. Each is a glycoprotein, synthesized by different types of cells, and …

May 27, 2021 · VWF-D′ makes extensive interactions with FVIII; visualization of FVIII-a3 showcases a central role of sulfated Y1680 in binding VWF R816. The structure of BIVV001 provides insights into the regulation of the FVIII-VWF complex and disease-causing mutations.

Human factor VIII (FVIII) functions as a cofactor for activated factor IX, and mutations in the FVIII gene (F8) result in hemophilia A. FVIII in plasma is proteolyzed and/or pinocytosed unless it is protected by non-covalent binding to soluble forms of von Willebrand factor (VWF) multimers.

Several novel recombinant FVIII (rFVIII) therapies for hemophilia A have been in clinical development, which aim to increase the half-life of FVIII (∼12 hours) and reduce dosing frequency by utilizing bioengineering techniques including PEGylation, Fc fusion, and single-chain design.

von Willebrand factor and FVIII are coexpressed in postcapillary high endothelial venules but not in most other ECs. Circulating factor VIII (FVIII) is derived from liver and from extrahepatic sources probably of endothelial origin, but the vascular sites of FVIII production remain unclear.

The extracellular association of FVIII with vWF may be necessary for efficient secretion of FVIII from its cell of origin. The thermodynamics, kinetics, and nature of the molecular contacts involved in the interaction have not been studied.