von Willebrand-factor
Biochemistry
| Synonym | Ristocetin-Cofactor (Factor VIII:RiCo) Factor VIII-associated antigen (Factor VIII:Ag) |
|---|---|
| Molecular weight | 500 - 20.000 kDa |
| Synthesis | Endothelial cells, megakaryocytes |
| Half-life | 6 - 12 hours |
| Plasma concentration | 5 - 10 mg/l |
| Normal range | 50 - 150% 0.5 - 1.5 E/ml (dependent of blood group) |
The von Willebrand-factor (vWF) is part of the factor VIII molecule complex. The vWF is formed by subunits of 220.000 Da that form dimers. Aggregates of 30-40 of these dimers form the multimer structure of the vWF-molecule. The vWF causes the adhesion of activated platelets to the subendothelium (damaged tissue wall) respectively the aggregation of platelets over the membrane receptors (Glycoprotein Ib and Glycoprotein IIb/IIIa), the so-called ristocetin-cofactor-function. Thus, the vWF has an important function in the primary haemostasis (temporary closure of a tissue wall damage with platelet aggregates). As carrier molecule for non-covalent bound factor VIII the vWF prevents its proteolytic degradation and secures the transport to places where factor VIII is necessary as cofactor to the plasmatic coagulation (secondary haemostasis).
Clinical significance
In most patients, the von Willebrand-syndrome disease (also called Willebrand-Jürgens-syndrome) leads to prolonged bleeding times. It is the most frequent congenital bleeding disorder and is distinguished as quantitative (Type I and III) and/or qualitative defects (Type II) in the vWF-molecule. The severity of the disease varies. Mild forms may be without symptoms. In severe cases surgery, tooth extractions and menstruation cause a risk of bleeding to death. Increased vWF-levels are seen e.g. as consequence of acute phases, stress situations and liver diseases (values to 1000%) as well as post-operatively and post-traumatically.
Indication
- Differential diagnosis between haemophilia A and von Willebrand-Syndrome
- Detection of acquired von Willebrand-Syndroms
- Additional diagnosis by liver- and vascular diseases
- Diagnosis of decreased proteolysis of vWF by Thrombotic-thrombocytopenic Purpura (TTP)
Literature
- Ginsburg D. The molecular biology of von Willebrand disease. Haemophilia 5 (Suppl. 2), 19-27, 1999.
- Federici AB, Mannucci PM. Diagnosis and management of von Willebrand disease. Haemophilia 5 (Suppl. 2), 28-37, 1999.
- Ingerslev J, Gürsel T. Diagnosis of von Willebrand disease. Haemophilia 5 (Suppl. 2), 50-56, 1999.
- Favaloro E et al. Laboratory Testing for von Willebrand's Disease: An Assessment of Current Diagnostic Practice and Efficacy by Means of a Multi-laboratory Survey. Thromb Haemost 82, 1276-82, 1999.
- Favaloro E. Collagen Binding Assay for von Willebrand Factor (VWF:CBA): Detection of von Willebrands Disease (VWD), and Discrimination of VWD Subtypes, Depends on Collagen Source. Thromb Haemost 83, 127-35, 2000.
- Lenting PJ, Casari C, Christophe OD, Denis CV. von Willebrand factor: the old, the new and the unknown. J Thromb Haemost. Dec 10(12), 2428-37, 2012