Can a 62-year-old woman with a family history of von Willebrand disease (VWD) still have the condition despite normal von Willebrand factor (VWF) activity to antigen ratio, given her low VWF levels?

Von Willebrand Disease in a 62-Year-Old Woman with Family History Despite Normal VWF Ratio

Yes, a 62-year-old woman with a family history of von Willebrand disease can still have the condition despite a normal VWF activity to antigen ratio of 1.0, especially if her VWF levels are low. 1

Diagnostic Considerations

Key Laboratory Findings

• The 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 2, 1

Why Low VWF with Normal Ratio Can Still Indicate VWD

1. Type 1 VWD Possibility:

   • Type 1 VWD is characterized by partial quantitative deficiency of VWF
   • Can present with proportionally reduced VWF:Ag and VWF:RCo (maintaining a normal ratio) 3
   • Low VWF levels (30-50 IU/dL) can be clinically significant 4

2. VWF as an Acute Phase Reactant:

   • VWF levels typically increase with age 1
   • The fact that this 62-year-old patient has low VWF levels despite her age is particularly concerning, as VWF levels should be higher in older individuals 1
   • VWF can be falsely elevated due to stress, inflammation, or other clinical conditions 1

3. Variability in Testing:

   • A single normal test does not rule out VWD, especially with strong family history
   • Guidelines recommend repeat testing up to 3 times to ensure reliable results 1

Clinical Approach

Assessment Algorithm

1. Evaluate Family History:

   • Confirmed family history of Type 2 VWD is highly significant
   • Consultation with a hematologist is recommended for patients with strong family history of VWD 1

2. Additional Testing to Consider:

   • Complete VWD evaluation requires:
     • Multimer analysis
     • RIPA testing
     • VWF:CB (collagen binding) assays 1
   • These specialized tests can detect subtle abnormalities not apparent in basic testing 2

3. Consider Low VWF as a Clinical Entity:

   • Patients with VWF levels between 30-50 IU/dL represent a diagnostic challenge
   • Some patients with "low VWF" have significant bleeding problems despite not meeting strict VWD criteria 4
   • Recent research suggests low VWF may be a complex disorder caused by variants in genes beyond VWF 4

Common Pitfalls and Caveats

1. Relying on a Single Test:

   • A normal VWF:RCo/VWF:Ag ratio alone does not rule out VWD 1
   • VWF levels can fluctuate, requiring repeat testing 1

2. Age Considerations:

   • VWF levels typically increase with age, so low levels in a 62-year-old are particularly noteworthy 1, 4
   • The discrepancy between expected age-related VWF increase and observed low levels strengthens the suspicion for VWD

3. Mixed VWD Phenotypes:

   • Some VWF gene mutations can have complex effects and give rise to mixed VWD phenotypes 3
   • This can complicate diagnosis and classification

4. Standardized Bleeding Assessment:

   • Use of a standardized bleeding assessment tool (BAT) is recommended to objectively quantify bleeding history 1
   • This can help correlate laboratory findings with clinical presentation

In conclusion, the combination of low VWF levels in a 62-year-old woman with a family history of VWD strongly suggests she may have VWD despite a normal VWF:RCo/VWF:Ag ratio. Further specialized testing is warranted, and consultation with a hematologist experienced in VWD diagnosis is recommended.