Do you agree that von Willebrand disease (VWD) is ruled out with a von Willebrand factor (VWF) level of 0.824 in a patient with a strong family history of type 2B von Willebrand disease?

Von Willebrand Disease Cannot Be Ruled Out Based Solely on a VWF Level of 0.824

A von Willebrand factor (VWF) level of 0.824 alone is insufficient to rule out type 2B von Willebrand disease (VWD), especially in a patient with strong family history of the condition. 1, 2

Diagnostic Approach for VWD

The diagnosis or exclusion of VWD requires more than a single VWF level measurement:

• Multiple tests are required: No single laboratory test can definitively screen for VWD 1, 2
• Initial VWD testing panel should include:
  • VWF antigen (VWF:Ag)
  • VWF activity (VWF:RCo or other platelet binding assay)
  • Factor VIII coagulant activity (FVIII)
  • Calculation of VWF:RCo/VWF:Ag ratio 1, 2

Why a Single VWF Level is Insufficient

For type 2B VWD specifically:

• The condition is characterized by qualitative defects in VWF rather than simply reduced levels
• Key diagnostic findings include:
  • VWF:RCo typically <30 IU/dL
  • VWF:Ag often 30-200 IU/dL (can be normal)
  • VWF:RCo/VWF:Ag ratio <0.5-0.7
  • Loss of high molecular weight multimers
  • Enhanced ristocetin-induced platelet aggregation (RIPA) at low doses 2

Important Considerations for This Case

1. Family history is critical: With multiple family members confirmed to have type 2B VWD, there is high pre-test probability 3

2. VWF is an acute phase reactant: Levels can be falsely elevated in response to stress, inflammation, pregnancy, or other clinical conditions 1

3. Type 2B VWD has variable presentation: Some patients with confirmed type 2B VWD can have:

   • Normal VWF:Ag levels
   • Normal VWF:RCo/VWF:Ag ratios in some cases
   • Even negative RIPA at standard concentrations 3

4. Complete VWD evaluation requires:

   • Multimer analysis to assess the distribution of VWF multimers
   • RIPA testing (especially at low concentrations)
   • VWF:CB (collagen binding) assays 1, 2

Recommended Next Steps

1. Complete the initial VWD testing panel if not already done:

   • VWF:RCo (or other activity assay)
   • FVIII activity
   • Calculate VWF:RCo/VWF:Ag ratio

2. Perform specialized testing:

   • VWF multimer analysis
   • RIPA at both standard and low ristocetin concentrations
   • VWF:CB assay

3. Consider repeat testing: VWF levels can vary, and testing may need to be repeated up to 3 times to ensure reliable results 1

4. Consult with a hematologist: Given the strong family history, consultation with a specialist in bleeding disorders is warranted 1, 2

Common Pitfalls to Avoid

• Relying on a single test: Diagnosis of VWD requires multiple complementary tests 1, 2
• Ignoring family history: A strong family history increases pre-test probability significantly 3
• Failing to consider VWF as an acute phase reactant: Elevated levels may mask underlying VWD 1
• Not testing for qualitative defects: Type 2 VWD often shows abnormal function despite near-normal antigen levels 2

The pathologist's conclusion that VWD is ruled out based solely on a VWF level of 0.824 is premature and potentially misleading, especially given the strong family history of type 2B VWD in this case.