Function of von Willebrand factor in haemostasis and thrombosis.
The physiological protection against bleeding is secured by platelet adhesion to the site of injury and sealing of the defect. The first step involves the arrest of platelets that have adhered to subendothelial structures, primarily collagen, at the site of injury. Under conditions of low shear rates, platelet adhesion to the damaged vessel wall is mediated by several proteins, including von Willebrand factor (VWF). However, under conditions of high shear, aggregation occurs only in the presence of soluble VWF. In solution, VWF becomes immobilized via its A3 domain on the fibrillar collagen of the vessel wall and acts as an intermediary between collagen and the platelet receptor glycoprotein Ibalpha (GPIbalpha), which is the only platelet receptor that does not require prior activation for bond formation. After GPIbalpha binds to the A1 domain of its main ligand VWF, further activation of the platelet via intracellular signalling occurs, allowing other receptors to engage VWF and collagen and thereby reinforcing permanent adhesion. On this first layer of adherent platelets, soluble VWF binds and uncoils, thereby attracting more platelets. Platelet interaction with immobilized and soluble VWF may also generate platelet-derived microparticles that exhibit pro-coagulant activity. Full growth of a multilayered platelet aggregate comprises binding of the platelet receptor integrin alphaIIbbeta3 to VWF and fibrinogen. In addition, the surface of the activated platelets accelerates the coagulation cascade, which, by its end product fibrin, stabilizes the growing platelet thrombus. This article summarizes the characteristics and role of VWF in the coagulation cascade.
Reininger
A J
AJ
Department of Transfusion Medicine and Haematology, University Clinic Munich, Munich, Germany. armin.reininger@med.uni-muenchen.de
D051722:ADAM Proteins / Q000502:physiology; D000071120:ADAMTS13 Protein; D001792:Blood Platelets / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D018056:Hemorheology / Q000502:physiology; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000097:blood; D019038:Platelet Glycoprotein GPIb-IX Complex; D013927:Thrombosis / Q000097:blood*; D014842:von Willebrand Diseases / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism / Q000502:physiology*
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human