What is the management for a patient with a suspected mild bleeding disorder, likely type 2 von Willebrand disease, with a normal von Willebrand antigen level but low ratio and normal restocetin platelet aggregation score?

Management of Suspected Type 2 von Willebrand Disease with Normal VWF Antigen and Low VWF:RCo/VWF:Ag Ratio

The patient most likely has Type 2M von Willebrand Disease and should be treated with desmopressin for minor bleeding episodes and VWF-containing concentrates for major bleeding or invasive procedures.

Diagnostic Assessment

Based on the laboratory findings, this patient presents with:

• Normal von Willebrand factor antigen (VWF:Ag) level
• VWF:RCo/VWF:Ag ratio of 0.7 (borderline low)
• Normal ristocetin platelet aggregation at low dose
• Normal platelet count (155)
• Family history (mother with similar ratio)

These findings are most consistent with Type 2M von Willebrand Disease (VWD), which is characterized by:

• Decreased VWF-dependent platelet adhesion without selective deficiency of high-molecular-weight VWF multimers
• VWF:RCo/VWF:Ag ratio typically <0.5-0.7 1, 2
• Normal to decreased VWF:Ag levels (30-200 IU/dL)

Management Recommendations

For Minor Bleeding Episodes:

1. Trial of desmopressin (DDAVP) - First-line therapy for most Type 2M VWD patients

   • Dosing: 0.3 μg/kg IV or subcutaneously
   • Monitor response with post-administration VWF levels
   • Caution: Risk of hyponatremia; fluid restriction recommended 3

2. Antifibrinolytic agents (adjunctive therapy)

   • Tranexamic acid: 1000-1300 mg orally three times daily or 10 mg/kg IV every 8 hours
   • Particularly useful for mucosal bleeding (epistaxis, menorrhagia)

For Major Bleeding or Invasive Procedures:

1. VWF-containing concentrates - Preferred for significant bleeding events 1, 4

   • Dosing based on weight and severity of bleeding
   • Target VWF:RCo levels >50 IU/dL for most procedures
   • For major surgeries, target levels >100 IU/dL initially, then >50 IU/dL for 7-14 days

2. Pre-procedural management:

   • For invasive procedures, VWF:RCo should be ≥50 IU/dL 1
   • Consider desmopressin trial before planned procedures if response is documented
   • For non-responsive patients, use VWF-containing concentrates

Special Considerations

Monitoring:

• Regular follow-up with hematology for assessment of bleeding symptoms
• Repeat VWF testing periodically as levels can fluctuate
• Consider formal bleeding assessment tool to quantify bleeding symptoms

Family Testing:

• Given the hereditary nature and maternal history, screening of first-degree relatives is recommended
• Genetic testing may help confirm the diagnosis and specific variant

Pregnancy Management:

• Close monitoring during pregnancy as VWF levels may change
• Consultation with high-risk obstetrics and hematology
• Prepare delivery plan with target VWF:RCo ≥50 IU/dL for vaginal delivery and ≥80 IU/dL for cesarean section 1

Pitfalls to Avoid

1. Misdiagnosis: Type 2M VWD can be confused with Type 1 or other Type 2 variants. The normal VWF:Ag with borderline low ratio suggests Type 2 rather than Type 1 1, 2.

2. Inadequate testing: Single measurements of VWF levels may be insufficient as levels fluctuate with stress, exercise, and hormonal status. Consider repeat testing if clinical suspicion remains high 5.

3. Inappropriate use of desmopressin: While useful in many Type 2M patients, desmopressin is contraindicated in Type 2B VWD as it can worsen thrombocytopenia 3, 6.

4. Overlooking platelet-type VWD: This rare disorder can mimic Type 2B VWD but requires different management. The normal platelet count and ristocetin response make this less likely 7.

5. Failure to provide prophylaxis: Patients undergoing procedures require adequate hemostatic coverage to prevent bleeding complications.

By following these management guidelines and avoiding common pitfalls, patients with suspected Type 2M VWD can receive appropriate care to minimize bleeding risk and improve quality of life.