P. J. Lenting (1), J. N. Pegon (1), E. Groot (2), P. G. de Groot (2)
(1) INSERM U.770 and Univ. Paris-Sud, 94276, Le Kremlin-Bicêtre, France; (2) Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands
The formation of thrombi is a multistep process involving several components, including von Willebrand factor (VWF). VWF is an adhesive multimeric protein, which acts as a molecular bridge between the subendothelial matrix and the glycoprotein Ib/IX/V receptor complex. Furthermore, VWF promotes the expansion of the platelet plug by cross-linking platelets via binding to integrin αIIbβ3. In terms of thrombus formation, it is essential that VWF-platelet interactions occur timely, that is: it should happen not too early or too late. Given the co-existence of VWF and platelets in the circulation, this implies that there must be regulatory mechanisms that prevent premature formation of VWF-rich platelet aggregates that could occlude the vasculature. Indeed, several mechanisms have been identified at the level of VWF, which are dedicated to the prevention of excessive VWF-platelet interactions following endothelial release of VWF (which may include limited exposure to shear stress, the presence of Mg2+ ions, inhibition of VWF-platelet interactions by endothelial proteins, ADAMTS13-mediated proteolysis) and of circulating VWF-platelet aggregates during normal circulation (shielding of the platelet-binding A1 domain by other regions of the VWF molecule, inhibition of VWF-platelet interactions by β2-glycoprotein I). In the present review an overview of these mechanisms will be discussed.
thrombosis, von Willebrand factor, von Willebrand disease
Tímea Szántó1,2, Ágota Schlammadinger3, Stephanie Staelens1, Simon F. De Meyer1, Kathleen Freson4, Inge Pareyn1, Stephan Vauterin1, Jolán Hársfalvi2, Hans Deckmyn1, Karen Vanhoorelbeke1
Thromb Haemost 2007 98 1: 178-185
Carolyn M. Millar1, Anne F. Riddell1, Simon A. Brown1, Richard Starke2, Ian Mackie2, Derrick J. Bowen3, P. Vincent Jenkins1, Jan A. van Mourik4
Thromb Haemost 2008 99 5: 916-924
Alessandra Casonato, Francesca Sartorello, Elena Pontara, Lisa Gallinaro, Antonella Bertomoro, Maria Grazia Cattini, Viviana Daidone, Maryta Szukowska, Antonio Pagnan
Thromb Haemost 2007 98 6: 1182-1187
The May 2013 issue of Thrombosis and Haemostasis 109.5 is a clinically relevant 'state of the art'...
Starting with the April 2013 issue of "Thrombosis and Haemostasis" TH109.4, the ESC...
The March 2013 issue TH 109.3 of Thrombosis and Haemostasis is a Theme Issue by Guest Editors...