von Willebrand Factor

A Marker of Endothelial Damage?

From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Department of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Milan, Italy.

Correspondence to P.M. Mannucci, Via Pace 9, 20122 Milano, Italy. E-mail PierMannuccio.Mannucci@unimi.it

Key Words: von Willebrand factor • endothelium • arterial thrombosis

Von Willebrand factor (vWF), a large glycoprotein encoded by a gene on chromosome 12, is synthesized by vascular endothelial cells and circulates in human plasma at concentrations of 10 µg/mL.¹ In plasma, vWF forms a noncovalent complex with coagulation factor VIII, the protein encoded by a gene on the X chromosome that is deficient or defective in hemophilia A.¹ This molecular complex is essential for normal survival of factor VIII, which is stabilized in the circulation, potentiated in its cofactor activity in clot formation, and protected from proteolytic inactivation.¹ The other important function of vWF in physiological hemostasis is in the formation of platelet plugs at sites of endothelial damage, in which the protein binds to the exposed subendothelium and forms a bridge between this surface and platelets.¹ These functions are facilitated by the peculiar structure of vWF, which is arranged in multimers of increasing size up to 2x10⁷ Da built up from a subunit of 2.5x10⁵ Da, and by its exposure on the platelet membrane to the glycoprotein complexes Ib/IX/V and IIb/IIIa, which function as receptors for vWF.¹ The importance of vWF in hemostasis is further supported by the fact that inherited deficiencies or dysfunctions of this protein cause a bleeding disorder called von Willebrand disease, relatively frequent in humans and animals.^{2 3}

vWF-mediated platelet adhesion to the injured endothelium is the first step in thrombus formation. That vWF plays a role in thrombosis is also supported by the demonstration that the largest multimeric forms of the glycoprotein aggregate platelets . . . [Full Text of this Article]

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