Inserm Unité 143, 80, rue du Général-Leclerc, 94276 Le Kremlin-Bicêtre, France, Laboratory for Thrombosis and Haemostasis, Dept. of Haematology, University Medical Center Utrecht, The Netherlands
- Key words: von Willebrand factor, von Willebrand disease, clearance, gene modifier, mutations, in vivo models
- Page(s) : 34-43
- Published in: 2006
Von Willebrand factor (FVW) is a multimeric plasma glycoprotein that plays two major roles in hemostasis: it promotes platelet adhesion to the subendothelium in case of vascular injury and it carries and protects coagulation FVIII in the circulation. FVW plasma concentration requires tight regulation since a reduced level may result in a bleeding tendency whereas an elevated concentration is associated with an increased thrombotic risk. Plasma levels represent a balance between biosynthetic and catabolic pathways. With regard to FVW, its biosynthetic pathways has been well studied in the past while relatively little is known concerning its clearance mechanism. However, recent data point to abnormal clearance as being a potential cause for von Willebrand disease, the most common inherited bleeding disorder in humans. Defective clearance may originate from a variety of reasons: mutations in the FVW gene, effect of a gene modifier or increase functionality of the FVW clearance mechanism. In this review, we will give an update of the present knowledge on how FVW is cleared from the circulation and how this process is regulated.