What are Willebrand factor (vWF) monomers?

Updated: Aug 01, 2019
  • Author: Carlos Solano Loran, MD; Chief Editor: Eric B Staros, MD  more...
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Answer

von Willebrand factor (vWF) is a large multimeric glycoprotein synthesized as a 2050 amino acid monomer in endothelium, megakaryocytes, and the subendothelial connective tissue. Every monomer contains particular binding domains that provide them the capacity to interact and bind other proteins specifically, factor VIII, collagen, and some platelet receptors.

Monomers undergo dimerization in the endoplasmic reticulum by N -glycosylation of their C-terminal ends and then move to the Golgi apparatus where multimers are assembled by cross-linking of cysteine residues at their N-terminal ends to form vWF multimers of increasing molecular weight. Multimers of high molecular weight have the greatest hemostatic capacity.

vWF plays a major role in blood hemostasis. In response to various stimuli, vWF is released from storage granules in platelets and endothelial cells to control bleeding. Its deficiency or qualitative defect leads to a bleeding tendency known as von Willebrand disease (vWD); however, given the hemostatic capacity of its largest multimers, defects in its catabolism can predispose to thrombogenic disorders, including thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome.

vWF also binds circulating factor VIII and prevents it peripheral degradation. Factor VIII is released from vWF by the action of thrombin.

The catabolism of vWF is mediated primarily by ADAMTS13, a metalloproteinase that cleaves vWF between tyrosine 842 and methionine 843 in the vWF A2 domain, generating a series of smaller multimers. It is this multimeric pattern that is analyzed in the laboratory.

In the absence of ADAMTS13, the cleavage of vWF does not occur and ultra-large vWF multimers appear in the plasma. The absence of ADAMTS13 and the generation of ultra-large vWF multimers are associated with thrombotic thrombocytopenic purpura. [5]

In a study of patients with acquired autoimmune thrombotic thrombocytopenic purpura, Béranger et al reported that assessment of the collagen-binding capacity of vWF (vWF:CB) can offer a more easily performed substitute for electrophoresis in determining the disease-associated loss of vWF high–molecular-weight multimers (vWF-HMWM). According to the investigators, enzyme-linked immunosorbent assay (ELISA), used to measure vWF:CB, revealed abnormally low levels of vWF-HMWM in 47.4% of the study’s patients, while electrophoresis found low values in 50% of patients. [6]


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