What is von Willebrand Disease?
Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting up to 1% of the population equally in males and females, caused by deficiency or dysfunction of von Willebrand factor (VWF)—a plasma glycoprotein essential for platelet adhesion at sites of vascular injury and for stabilizing coagulation factor VIII (FVIII) in circulation. 1
Pathophysiology
VWF serves two critical hemostatic functions that explain the bleeding manifestations when deficient or dysfunctional 1:
- Mediates platelet adhesion and aggregation at sites of blood vessel injury, forming the initial hemostatic plug 1, 2
- Carries and stabilizes factor VIII in the bloodstream, preventing its premature degradation 1, 3
Clinical Manifestations
Common Bleeding Symptoms
Patients with VWD typically present with mucocutaneous bleeding patterns 2:
- Easy bruising (ecchymoses) 1
- Nosebleeds (epistaxis) 1, 2
- Gingival bleeding 1
- Prolonged bleeding from minor wounds 2
- Heavy menstrual bleeding (menorrhagia) in women 1
- Postpartum hemorrhage 1, 2
- Bleeding following surgery or invasive procedures (including dental extractions) 1
Less Common Manifestations
- Gastrointestinal bleeding 1, 2
- Hematomas or hemarthroses (joint bleeding) 1, 2
- Hemoptysis 1
- Central nervous system bleeding 1
Classification System
VWD is categorized into three main types based on whether the defect is quantitative or qualitative 1:
Type 1 VWD (Partial Quantitative Deficiency)
- Accounts for ~75% of symptomatic cases 1
- Partial decrease in VWF levels (typically <50 IU/dL) 4
- Symptoms range from mild to moderate bleeding 1
- Mildest forms (VWF levels 30-50 IU/dL) usually have minimal bleeding 4
Type 2 VWD (Qualitative Deficiency)
Comprises four distinct subtypes with functional abnormalities 1:
- Type 2A: Most common Type 2 variant 1
- Type 2B: Less common 1
- Type 2M: Less common 1
- Type 2N: Defective FVIII binding 1, 4
Type 3 VWD (Complete Quantitative Deficiency)
- Virtually complete absence of VWF (undetectable levels) 1, 4
- Rare, affecting only ~1 in 1,000 persons 1
- Severe, life-threatening bleeding manifestations 1, 4
Acquired von Willebrand Syndrome (AVWS)
AVWS is less common than hereditary VWD and differs in several key aspects 1:
- Associated with various medical conditions and mechanisms rather than genetic inheritance 1
- Laboratory findings similar to hereditary VWD 1
- Should be suspected when abnormal VWF test results and bleeding symptoms occur without personal or family history consistent with hereditary VWD 1
- Consider AVWS testing when bleeding occurs in association with causative medical conditions 1
Clinical Pitfalls and Caveats
Risk of Misdiagnosis
VWD is at risk of misdiagnosis, overdiagnosis, and underdiagnosis due to 2:
- Complex diagnostic requirements
- Variable bleeding symptom presentation
- External variables affecting VWF levels (blood type, exercise, thyroid hormones, estrogens, aging)
- Lack of disease awareness among non-specialist providers
Gender-Specific Considerations
VWD may be disproportionately symptomatic in women of childbearing age due to menorrhagia and postpartum bleeding risks 5. This can lead to delayed diagnosis if bleeding symptoms are attributed solely to gynecologic causes rather than an underlying bleeding disorder.
Severity Spectrum
Not all Type 1 VWD patients require aggressive management—those with VWF levels between 30-50 IU/dL typically have the mildest bleeding phenotype 4. This is important for avoiding overtreatment while ensuring appropriate perioperative management.