What is von Willebrand factor?

Von Willebrand Factor (VWF)

Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that mediates platelet adhesion and aggregation at sites of vascular injury, and also carries and stabilizes coagulation factor VIII (FVIII) in the circulation, playing a crucial role in normal hemostasis. 1

Structure and Function

• VWF is a large, complex glycoprotein assembled from identical ~250 kDa subunits into disulfide-linked multimers that can exceed 20,000 kDa in size 2
• VWF has two primary hemostatic functions:
  • It mediates platelet adhesion to sites of vascular damage and promotes platelet-to-platelet cohesion during thrombus formation 3
  • It serves as a carrier protein for blood clotting factor VIII, which is essential for factor VIII survival in circulation 1, 3
• VWF's activity appears to be regulated by allosteric mechanisms and possibly by hydrodynamic shear forces 2
• The protein is particularly important in high shear stress conditions, such as in capillaries under physiologic conditions or in stenosed arteries 4

Distribution and Synthesis

• VWF is present in blood plasma, inside platelets, within endothelial cells, and in the subendothelial matrix of vessel walls 4
• The complex biosynthetic process of VWF involves assembly, intracellular targeting, and secretion of VWF multimers 2
• VWF levels can vary in response to clinical status as it is an acute phase reactant 1
• VWF has a relatively short half-life of 8-12 hours after infusion, compared to other coagulation factors 1

Clinical Significance

• Deficiency or dysfunction of VWF results in von Willebrand disease (VWD), the most common inherited bleeding disorder, affecting approximately 1% of the general population 1
• VWD can be classified into three main types 1:
  • Type 1: Partial quantitative deficiency (accounts for ~75% of symptomatic cases)
  • Type 2: Qualitative deficiency with four subtypes (2A, 2B, 2M, 2N)
  • Type 3: Virtually complete quantitative deficiency (rare, affecting ~1 in 1,000)
• VWD can also occur as an acquired disorder (acquired von Willebrand syndrome or AVWS) associated with various medical conditions 1
• Common bleeding symptoms in VWD include easy bruising, nosebleeds, mucosal bleeding, gastrointestinal bleeding, and heavy menstrual bleeding in women 1
• Severity ranges from mild bleeding in Type 1 VWD to severe, life-threatening bleeding in Type 3 VWD 1

Beyond Hemostasis

• VWF is increasingly recognized as a multifunctional protein involved in processes beyond hemostasis 5
• These additional roles include participation in angiogenesis, cell proliferation, inflammation, and tumor cell survival 5

Diagnostic Considerations

• Diagnosis of VWD can be challenging and may require multiple tests to evaluate the various functions of VWF 6
• VWF levels can fluctuate as an acute phase reactant, potentially resulting in falsely elevated results during stress or inflammation 1
• Testing may need to be repeated up to 3 times to ensure reliable results 1
• Intracranial hemorrhage (ICH) is extremely rare in VWD, making it an unlikely cause of spontaneous ICH 1

Treatment Implications

• FVIII/VWF concentrates are used in the treatment of VWD, particularly in Type 3 and in Type 1 or 2 patients who don't respond to desmopressin (DDAVP) 3
• The presence of the physiologic FVIII/VWF complex is also important in replacement therapy for patients with hemophilia A 3