What does testing and management look like for an individual with a positive von Willebrand (vW) test result?

Testing and Management for Positive von Willebrand Disease

Testing for von Willebrand disease (VWD) requires comprehensive laboratory evaluation including CBC, PT, aPTT, VWF:Ag, VWF:RCo, and FVIII activity, with careful attention to proper sample collection and handling to avoid false results. 1, 2

Initial Diagnostic Testing

First-Line Laboratory Tests

• Complete blood count (CBC)
• Prothrombin time (PT)
• Activated partial thromboplastin time (aPTT)
• Von Willebrand factor antigen (VWF:Ag)
• Von Willebrand factor ristocetin cofactor activity (VWF:RCo)
• Factor VIII coagulant activity (FVIII:C) 1, 2

Critical Sample Collection Considerations

• Atraumatic blood draw to minimize tissue factor exposure
• Transport samples at room temperature (not cold)
• Process plasma promptly at room temperature
• Thoroughly centrifuge to remove platelets
• If not testing within 2 hours, freeze at or below -40°C 2

Factors That May Affect Test Results

• Patient stress or anxiety (falsely elevates VWF)
• Recent exercise (elevates VWF)
• Inflammatory conditions (elevate VWF)
• Pregnancy or estrogen use (elevate VWF)
• ABO blood type (Type O individuals have ~25% lower VWF levels)
• Ethnicity (African-Americans have higher baseline VWF levels) 1, 2

Classification and Interpretation

Based on test results, VWD is classified into:

1. Type 1 VWD (~75% of cases)

   • Partial quantitative deficiency
   • Reduced VWF:Ag and VWF:RCo levels
   • Normal VWF:RCo/VWF:Ag ratio

2. Type 2 VWD

   • Qualitative deficiency with four subtypes:
     • Type 2A: Decreased high-molecular-weight multimers
     • Type 2B: Increased affinity for platelets
     • Type 2M: Decreased platelet-dependent function
     • Type 2N: Decreased FVIII binding

3. Type 3 VWD (rare, ~1 in 1,000)

   • Complete or near-complete absence of VWF
   • Very low FVIII levels 1, 3

Additional Testing When Needed

If initial results are borderline or inconclusive:

• Repeat VWF testing (single tests are insufficient)
• VWF multimer analysis
• VWF collagen binding assay
• Ristocetin-induced platelet aggregation (RIPA)
• VWF:FVIII binding assay
• VWF propeptide measurement
• Genetic testing of VWF gene (particularly helpful for Type 2 variants) 1, 4, 5

Management Approaches

Treatment options depend on VWD type and severity:

1. Desmopressin (DDAVP)

   • First-line therapy for most Type 1 and some Type 2 VWD
   • Releases stored VWF from endothelial cells
   • Use with caution in older patients due to risk of hyponatremia 6

2. VWF-containing concentrates

   • Plasma-derived or recombinant VWF
   • Used for Type 3 VWD, severe Type 1, most Type 2 variants
   • Required for major surgeries or severe bleeding
   • Use with caution in older patients with cardiovascular risk 3, 6

3. Adjunctive therapies

   • Antifibrinolytic agents (tranexamic acid, aminocaproic acid)
   • Topical hemostatic agents
   • Hormonal therapies for menorrhagia 3

Common Pitfalls and Caveats

• Misdiagnosis risk: VWD is frequently misdiagnosed, overdiagnosed, or underdiagnosed 3
• Bleeding assessment tools: Using validated bleeding assessment tools improves screening accuracy (75% sensitivity, 54% specificity) 7
• Medication interference: Discontinue platelet-affecting medications 7-10 days before testing 2
• Age considerations: VWF levels increase with age, potentially masking mild VWD in older patients 6
• Repeat testing: VWD testing should be repeated if initial results are borderline or inconclusive 2
• Special populations: Pregnancy, surgery, and aging can all affect VWD manifestation and management 6

Special Considerations for Aging Patients

• VWF levels naturally increase with age, potentially reducing symptoms in mild cases
• Gastrointestinal bleeding and hematuria become more challenging bleeding sites
• Cardiovascular disease management is complex due to antiplatelet therapy needs
• Desmopressin should be used cautiously due to increased risk of hyponatremia and cardiovascular events 6