Von willebrand factor

The von Willebrand factor, a glycoprotein, mediates platelet aggregation by attaching to the GPlb and GPllb/GPIIIa receptors of platelets after their activation. Furthermore, the von Willebrand factor, after attachment to the platelets, mediates the adhesion of the platelets to the exposed collagen fibrils of the subendothelium in the area of a vessel injury site.

The von Willebrand factor is synthesized in the endothelial cells and in the megakaryocytes. First, a monomer consisting of 2813 amino acids with a molecular weight of 360 kD is formed. These monomers are polymerised into multimers with a molecular weight of between 500 and 20,000 kD. The von Willebrand factor is partly released into the plasma, partly it is initially stored in endothelial cells in the so-called Weibel-Palade corpuscles or in the alpha granules of the thrombocytes.

Platelets activated by thrombin, plasmin and fibrin release a lysophospholipid, the sphingosine-1-phosphate. Sphingosine-1-phosphate causes the release of von Willebrand factor from the Weibel palate corpuscles. This circulates in the plasma as a complex with factor VIII. The complex formation protects factor VIII from degradation by the more active protein C.

In the event of an injury, the binding of von Willebrand factor to the exposed collagen simultaneously brings factor VIII to the site of the injury. After their secretion, the high molecular weight components of von Willebrand factor are very active in clotting and bind to the thrombocytes even under the slightest shear forces.

Under physiological conditions, the von Willebrand factor is enzymatically cleaved into smaller fragments by a protease immediately after its secretion from the endothelia in order to maintain homeostasis. A malfunction of this splitting protease leads to Moschcowitz disease and hemolytic uremic syndrome (HUS).

The concentration of von Willebrand factor increases with age and is significantly higher in patients taking diuretics, digitalis, heparin or oral anticoagulants compared to other patients. Patients with an elevated von Willebrand factor concentration have a 1 to 2-fold increased risk of conor heart disease.

1. Hantschke M et al (2016) Immunohistological techniques. In: L. Cerroni et al. histopathology of the skin. Springer Publishing House Berlin-Heidelberg p. 33.
2. HA Neumann (2014) The coagulation system. ABW-Scientific Publisher GmbH Berlin