What is the significance and management of a Von Willebrand factor (VWF) level of 36%?

Significance and Management of Von Willebrand Factor Level of 36%

A von Willebrand factor (VWF) level of 36% indicates low VWF, which falls between normal levels and definite von Willebrand disease (VWD), and requires clinical management based on bleeding history and risk assessment. 1

Classification and Diagnosis

VWF levels of 36% fall into a specific diagnostic category:

• This level is above the definitive cutoff for Type 1 VWD (<30 IU/dL or 30%) but below normal range (50-200 IU/dL) 1
• Classified as "low VWF" (30-50 IU/dL) rather than definite VWD 2
• This intermediate category has variable bleeding phenotypes and often lacks detectable VWF gene mutations 3

Additional Testing Needed

• VWF:RCo (ristocetin cofactor activity) to assess VWF function
• VWF:Ag (antigen) to quantify VWF protein
• FVIII level, as VWF is a carrier protein for FVIII
• VWF:RCo/VWF:Ag ratio to distinguish between quantitative and qualitative defects (ratio >0.5-0.7 suggests quantitative deficiency) 1

Clinical Significance

The clinical significance of VWF level 36% depends on:

1. Bleeding History:

   • Presence of mucocutaneous bleeding (epistaxis, easy bruising, gingival bleeding)
   • Prolonged bleeding from minor wounds
   • Heavy menstrual bleeding in women
   • Post-surgical bleeding episodes 4

2. Family History:

   • Family members with diagnosed bleeding disorders
   • Family history of excessive bleeding with procedures 1

3. Bleeding Assessment Tool (BAT):

   • A structured assessment of bleeding symptoms should be performed
   • However, BAT should not be the sole determinant for ordering further testing 1

Management Approach

For Minor Procedures/Surgeries:

• First-line prophylaxis: Tranexamic acid (antifibrinolytic) 1
• If bleeding occurs: Consider DDAVP (desmopressin) 1

For Major Surgeries:

• Prophylaxis: Combination of tranexamic acid and DDAVP 1
• If bleeding occurs: Consider platelets, fresh frozen plasma, or other blood products based on clinical response 1

For Women with Heavy Menstrual Bleeding:

• Check ferritin levels (iron deficiency is common) 1
• Consider hormonal therapies (combined oral contraceptives)
• Tranexamic acid during menstruation 1

For Pregnancy/Delivery:

• Prophylactic tranexamic acid is recommended (used by 58% of clinicians) 1
• DDAVP may be added if needed (used by 9% of clinicians in combination with antifibrinolytics) 1

Important Considerations

• Medication Interactions: Avoid medications that impair platelet function (NSAIDs, aspirin) 1
• Antidepressants: If needed, bupropion is considered safer than SSRIs, which can increase bleeding risk 4
• ABO Blood Group: May influence VWF levels but blood group-specific reference ranges are not recommended for diagnosis 1
• Repeat Testing: VWF levels can fluctuate with stress, exercise, pregnancy, and inflammation, so repeat testing may be necessary 1

Pitfalls to Avoid

1. Misclassification: Don't automatically classify as "normal" since 36% is below normal range but above definitive VWD cutoff 5
2. Ignoring Clinical History: Bleeding history is crucial for management decisions, regardless of VWF level 5
3. Sample Handling: Improper processing can affect results; samples should be processed promptly at room temperature and frozen at -40°C if not tested within 2 hours 1
4. Overlooking Iron Deficiency: Check ferritin levels, as iron deficiency is common in patients with low VWF 1
5. Assuming No Risk: Even with borderline levels, patients may have significant bleeding with surgery or trauma 3

This level requires clinical correlation and potentially prophylactic management for invasive procedures, even though it doesn't meet the strict criteria for definitive VWD.