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Annual Review of Biochemistry

Volume 67, 1998

BIOCHEMISTRY AND GENETICS OF VON WILLEBRAND FACTOR

Abstract

Von Willebrand factor (VWF) is a blood glycoprotein that is required for normal hemostasis, and deficiency of VWF, or von Willebrand disease (VWD), is the most common inherited bleeding disorder. VWF mediates the adhesion of platelets to sites of vascular damage by binding to specific platelet membrane glycoproteins and to constituents of exposed connective tissue. These activities appear to be regulated by allosteric mechanisms and possibly by hydrodynamic shear forces. VWF also is a carrier protein for blood clotting factor VIII, and this interaction is required for normal factor VIII survival in the circulation. VWF is assembled from identical ≈250 kDa subunits into disulfide-linked multimers that may be >20,000 kDa. Mutations in VWD can disrupt this complex biosynthetic process at several steps to impair the assembly, intracellular targeting, or secretion of VWF multimers. Other VWD mutations impair the survival of VWF in plasma or the function of specific ligand binding sites. This growing body of information about VWF synthesis, structure, and function has allowed the reclassification of VWD based upon distinct pathophysiologic mechanisms that appear to correlate with clincial symptoms and the response to therapy.

Keyword(s): factor VIII, hemostasis, platelet adhesion, von Willebrand disease, Weibel-Palade body
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1998-07-01
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BIOCHEMISTRY AND GENETICS OF VON WILLEBRAND FACTOR
Annual Review of Biochemistry 67, 395 (1998); https://doi.org/10.1146/annurev.biochem.67.1.395
/content/journals/10.1146/annurev.biochem.67.1.395
/content/journals/10.1146/annurev.biochem.67.1.395
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