What is the role of Von Willebrand Factor (VWF) in coagulation?

From the Guidelines

Von Willebrand factor (VWF) plays a crucial role in coagulation by helping platelets stick to damaged blood vessels and promoting blood clotting, and its deficiency can lead to Von Willebrand disease, a common inherited bleeding disorder. The role of VWF in coagulation is multifaceted, including binding to factor VIII to protect it from degradation and helping platelets adhere to damaged blood vessel walls, making it essential for proper hemostasis 1. VWF deficiency can cause a range of symptoms, including easy bruising, nosebleeds, heavy menstrual periods, and prolonged bleeding after injury or surgery, and treatment depends on disease severity, with options including desmopressin (DDAVP) or VWF replacement therapy such as Humate-P, Wilate, or Vonvendi 1. Recent studies have also highlighted the importance of VWF in acquired von Willebrand syndrome during extracorporeal membrane oxygenation support, with VWF-containing concentrates, such as plasma-derived VWF (pdVWF) and recombinant human VWF (rVWF), being used to treat AVWS-related bleeding 1. Some key points to consider when evaluating the role of VWF in coagulation include:

• VWF is a blood protein that helps platelets stick to damaged blood vessels and promotes blood clotting
• VWF deficiency can cause Von Willebrand disease, a common inherited bleeding disorder
• Treatment options for VWF deficiency include desmopressin (DDAVP) or VWF replacement therapy such as Humate-P, Wilate, or Vonvendi
• VWF-containing concentrates, such as pdVWF and rVWF, can be used to treat AVWS-related bleeding
• The efficacy of VWF concentrates in ECMO patients who develop AVWS may be limited due to the high shear stress within the device, which could result in proteolysis of the infused VWF by ADAMTS-13. Overall, VWF plays a critical role in coagulation, and its deficiency can have significant consequences, making it essential to understand its function and treatment options.

From the Research

Role of Von Willebrand Factor in Coagulation

• Von Willebrand Factor (VWF) plays a crucial role in coagulation by mediating the initial adhesion of platelets at sites of vascular injury and binding and stabilizing coagulation factor VIII (FVIII) in the blood 2.
• VWF is a multi-adhesive protein that binds platelets to exposed subendothelium and carries factor VIII in circulation, and its deficiency or abnormal activity is responsible for von Willebrand disease, the most frequent inherited bleeding disorder 3.
• The aim of treatment for von Willebrand disease is to correct the dual defects of haemostasis, i.e. abnormal coagulation expressed by low levels of factor VIII (FVIII) and abnormal platelet adhesion expressed by a prolonged bleeding time (BT) 4.
• VWF facilitates platelet adhesion and aggregation, and serves to increase potentially low coagulation factor VIII (FVIII) in plasma, and therapy for von Willebrand disease aims to restore the hemostatic function conferred by VWF 5.

Mechanism of Action

• VWF binds to platelets and helps them to adhere to the site of injury, and also binds to and stabilizes FVIII, which is essential for the coagulation cascade 6, 2.
• The high molecular weight VWF multimers are most effective in restoring hemostasis, and the efficacy of VWF/FVIII concentrates depends on the content and quality of VWF and FVIII 5.
• Dosing of VWF/FVIII concentrates is generally consistent across VWD subtypes, although patients with severe phenotypes or undergoing major procedures may require more infusions or longer treatment duration 5.

Clinical Implications

• The diagnosis and management of von Willebrand disease require consideration of the individual situation, including the type of procedure and the bleeding rate, before decisions about treatment type, dose, duration and adjunctive therapy can be made 2.
• Desmopressin is the treatment of choice for type 1 von Willebrand disease, but in patients unresponsive to desmopressin, the preferred treatment is with plasma-derived VWF-containing FVIII concentrates 6, 5.
• Laboratory monitoring of efficacy and safety issues such as thrombosis risk and thromboprophylaxis are important considerations for the use of VWF-containing concentrates 5.