From the Guidelines
Von Willebrand factor (VWF) plays a crucial role in blood coagulation by mediating platelet adhesion and accumulation at sites of blood vessel injury, and also carrying coagulation factor VIII (FVIII) that is important for generating procoagulant activity. When blood vessel injury occurs, VWF binds to exposed collagen in the vessel wall and undergoes a conformational change that allows platelets to adhere to it via their GPIb receptors, as described in the study by 1. This initial platelet adhesion is especially important in high-flow environments like arteries where other platelet adhesion mechanisms are less effective. Some key points about VWF's role in coagulation include:
- Mediating platelet adhesion and accumulation at sites of blood vessel injury
- Carrying coagulation factor VIII (FVIII) that is important for generating procoagulant activity, as noted in the study by 1
- Protecting Factor VIII from premature degradation and extending its half-life in circulation
- Maintaining adequate levels of Factor VIII in the bloodstream until it's needed for coagulation Without sufficient VWF, patients experience bleeding disorders due to impaired platelet adhesion and reduced Factor VIII levels, as seen in von Willebrand disease, the most common inherited bleeding disorder, which is discussed in the studies by 1.
From the Research
Role of von Willebrand Factor in Coagulation
- von Willebrand factor (vWF) has essential functions in the first stage of hemostasis, facilitating the adhesion of platelets to exposed collagens at the site of vascular damage 2
- vWF acts as a link between platelets in the forming thrombus, promoting platelet aggregation 2, 3
- vWF binds and stabilizes factor VIII procoagulant protein, contributing to its stability and function in the generation of fibrin 4, 3, 5
- The interaction between vWF and factor VIII plays a major role in the hemostatic system, with vWF protecting factor VIII from proteolytic degradation 4
- vWF deficiency, either quantitative or qualitative, results in von Willebrand disease (VWD), the most common bleeding disorder 4, 5
Mechanism of Action
- vWF is synthesized in endothelial cells and megakaryocytes as a large polymer composed of identical subunits 3
- The size of circulating vWF multimers is controlled by proteolytic cleavage carried out by a specific protease 3
- vWF binds to extracellular matrix components and cell membrane receptors, promoting the initial tethering and adhesion of platelets to subendothelial surfaces 3
- vWF also binds to factor VIII, contributing to its stability and function in the generation of fibrin 3, 5
Clinical Significance
- von Willebrand disease (VWD) is the most common congenital bleeding disorder in humans, caused by quantitative and qualitative abnormalities of vWF 5
- The treatment of VWD aims to correct the dual defect of hemostasis, including the abnormal platelet adhesion and coagulation expressed by low levels of factor VIII 6
- Desmopressin (DDAVP) is a treatment option for type 1 VWD, inducing the release of normal vWF from cellular compartments 6