Track topics on Twitter Track topics that are important to you
von Willebrand factor (VWF) binds to platelets and collagen as a means of facilitating coagulation at sites of injury. Recent evidence has shown that myosin can serve as a surface for thrombin generation and binds to activated factor V and factor X. We studied whether VWF can also bind myosin as a means of bringing factor VIII (FVIII) to sites of clot formation. A myosin-binding assay was developed using skeletal muscle myosin to measure VWF binding, and plasma-derived and recombinant VWF containing molecular disruptions at key VWF sites were tested. Competition assays were performed using anti-VWF antibodies. FVIII binding to myosin was measured using a chromogenic FVIII substrate. Thrombin generation was measured using a fluorogenic substrate with and without myosin. Wild-type recombinant VWF and human plasma VWF from healthy controls bound myosin, whereas plasma lacking VWF exhibited no detectable myosin binding. Binding was multimer dependent and blocked by anti-VWF A1 domain antibodies or A1 domain VWF variants. The specific residues involved in myosin binding were similar, but not identical, to those required for collagen IV binding. FVIII did not bind myosin directly, but FVIII activity was detected when VWF and FVIII were bound to myosin. Myosin enhanced thrombin generation in platelet-poor plasma, although no difference was detected with the addition of myosin to platelet-rich plasma. Myosin may help to facilitate delivery of FVIII to sites of injury and indirectly accelerate thrombin generation by providing a surface for VWF binding in the setting of trauma and myosin exposure.
This article was published in the following journal.
Name: Blood advances
Proteolytic cleavage of von Willebrand factor (VWF) by a plasma a disintegrin and metalloproteinase with a thrombospondin type 1 motifs, member 13 (ADAMTS13) is regulated by shear stress and bindin...
Association of moyamoya disease (MMD) with von Willebrand disease (vWD) is extremely rare. We first report a 27-year-old female case of MMD concurrent with vWD type 1, which presented as hemorrhagic s...
The identity of the amino acid regions of factor VIII (FVIII) that contribute to factor IXa (FIXa) and Von Willebrand Factor (VWF) binding has not been fully resolved. Previously, we observed that rep...
The proband's von Willebrand factor (VWF) antigen and VWF collagen-binding capacity were 14% and 10%, respectively; his sister's were 16% and 9%, respectively; and his nephew's were 30% and 15%, respe...
: Angiodysplastic (AD) lesion is the most common cause of recurrent gastrointestinal (GI) bleeding in inherited Von Willebrand disease (VWD) patients lacking high-molecular-weight multimers. Defect or...
OBJECTIVES: I. Evaluate the effect of a new von Willebrand factor concentrate on bleeding time, in vivo recovery, and circulating half-life of the infused factor in patients with von Will...
The Low Von Willebrand in Ireland Cohort (LoVIC) study focuses on the bleeding phenotype and biological mechanisms underlying low Von Willebrand Factor (VWF) levels.
The purpose of this phase 3 study is to investigate the efficacy and safety, including immunogenicity and thrombogenicity of prophylactic treatment with recombinant von Willebrand factor (...
During treatments with extracorporeal circuits such as extracorporeal membrane oxygenation (ECMO) degradation of high molecular weight (HMW) of von Willebrand factor (vWF) multimers occur ...
Von Willebrand Disease (VWD) is defined as an inherited bleeding disorder that is caused by deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates the ini...
Blood-coagulation factor VIII. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin.
A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor.
A subtype of von Willebrand disease that results from a partial deficiency of VON WILLEBRAND FACTOR.
A subtype of von Willebrand disease that results from qualitative deficiencies of VON WILLEBRAND FACTOR. The subtype is divided into several variants with each variant having a distinctive pattern of PLATELET-interaction.
A subtype of von Willebrand disease that results from a total or near total deficiency of VON WILLEBRAND FACTOR.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
An assay is an analytic procedure for qualitatively assessing or quantitatively measuring the presence or amount or the functional activity of a target entity. This can be a drug or biochemical substance or a cell in an organism or organic sample. ...
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...