Von Willebrand Disease: Protein Deficiency
Individuals with von Willebrand disease (VWD) have defects in von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion and factor VIII stabilization. 1
The Defective Protein: Von Willebrand Factor
VWF is a complex multimeric glycoprotein that serves two critical hemostatic functions 2, 3:
- Primary function: Forms a bridge between platelets and areas of vascular damage, enabling platelet adhesion to exposed subendothelium after vascular injury 2, 4
- Secondary function: Binds to and stabilizes factor VIII in circulation, preventing its rapid degradation 2, 5
Types of VWF Defects
The defects in VWF can be either quantitative or qualitative 1:
Quantitative Deficiencies
- Type 1 VWD: Partial quantitative deficiency with VWF levels <30 IU/dL but functionally normal protein (VWF:RCo/VWF:Ag ratio >0.5-0.7) 1
- Type 3 VWD: Virtually complete deficiency with VWF levels <3 IU/dL, representing the most severe form 1, 2
Qualitative Defects
- Type 2 variants: Qualitative abnormalities in VWF structure or function, including subtypes 2A, 2B, 2M, and 2N, each with distinct functional impairments 1, 4
Clinical Consequences of VWF Deficiency
The dual defect in hemostasis results from 6, 5:
- Impaired platelet adhesion at sites of vascular injury due to defective or deficient VWF
- Secondary factor VIII deficiency because VWF normally carries and stabilizes factor VIII in circulation; when VWF is deficient or dysfunctional, factor VIII levels drop secondarily 6, 5
This explains why VWD patients present with mucocutaneous bleeding patterns (easy bruising, heavy menstrual bleeding, nosebleeds, bleeding after dental procedures) and may have mildly prolonged aPTT with decreased factor VIII activity 6, 4.