VWF Multimer Testing Should Be Pursued for This Family with Bleeding Symptoms and Abnormal VWF Ratio
Yes, you should appeal the cancellation of the multimer test, as it is essential for proper subtyping of potential Type 2 von Willebrand Disease in this family with multiple bleeding symptoms and an abnormal VWF antigen to activity ratio of 0.7. 1
Clinical Presentation Analysis
The family's presentation strongly suggests a bleeding disorder that requires complete investigation:
- Multiple family members with hemorrhage episodes
- Normal von Willebrand factor levels in two members (one at 1.33)
- Abnormal VWF antigen to activity ratio of 0.7 in two members
- Family history of iron deficiency (even in post-menopausal women)
- Increased bleeding scores on the bleeding assessment tool (BAT) in at least six family members
- Normal RIPA test with platelet level of 155
Diagnostic Significance of VWF Multimer Analysis
The VWF multimer analysis is critical in this case for several reasons:
Essential for VWD subtyping: According to the American Society of Hematology guidelines, VWF multimer analysis is necessary for subtyping von Willebrand Disease, particularly for Type 2 variants 1
Abnormal VWF:RCo/VWF:Ag ratio: The ratio of 0.7 is at the borderline cutoff value that suggests Type 2 VWD, which requires multimer analysis for confirmation 1
Normal RIPA with abnormal bleeding: This combination suggests a possible qualitative defect in VWF that would only be detected through multimer analysis 2
Diagnostic Algorithm for This Family
- Initial findings: Abnormal VWF:Ag/activity ratio of 0.7 with normal VWF levels
- Clinical correlation: Multiple family members with elevated bleeding scores
- Next diagnostic step: VWF multimer analysis to determine if there is a qualitative VWF defect (Type 2 VWD)
Type 2 VWD Considerations
The family's presentation is consistent with possible Type 2 VWD:
| Subtype | Key Laboratory Findings | Clinical Features |
|---|---|---|
| Type 2A | • VWF:RCo/VWF:Ag <0.5-0.7 • Loss of high & intermediate MW multimers |
• Moderate to severe bleeding |
| Type 2M | • VWF:RCo/VWF:Ag <0.5-0.7 • Normal multimer pattern |
• Variable bleeding |
Without the multimer analysis, it's impossible to differentiate between these subtypes, which have different treatment approaches 1.
Clinical Implications of Proper Diagnosis
Identifying the specific bleeding disorder is crucial for:
Treatment planning: Different subtypes respond differently to desmopressin (DDAVP) - Type 2M may respond to DDAVP while Type 2A often requires VWF-containing concentrates 1, 3
Genetic counseling: Proper subtyping allows for appropriate genetic counseling for family members 1
Perioperative management: Specific VWD subtype diagnosis guides prophylactic treatment before procedures 4
Management of iron deficiency: The family history of iron deficiency, even in post-menopausal women, suggests chronic blood loss that needs proper management 1
Common Pitfalls to Avoid
Relying solely on VWF levels: Normal VWF levels don't exclude VWD, especially Type 2 variants where the problem is qualitative 2
Misinterpreting borderline ratios: A VWF:RCo/VWF:Ag ratio of 0.7 is at the borderline cutoff and should prompt further investigation, not dismissal 1
Overlooking family bleeding history: The strong family history of bleeding and iron deficiency is significant even with some normal laboratory values 5
Incomplete testing: According to the NHLBI VWD Guidelines, comprehensive testing is needed when clinical suspicion is high 2, 6
Conclusion for Clinical Action
The multimer test cancellation should be appealed based on:
- The borderline VWF:RCo/VWF:Ag ratio of 0.7
- Multiple family members with elevated bleeding scores
- Family history of iron deficiency
- Need for proper subtyping to guide treatment decisions
Without multimer analysis, this family may be left with an incomplete diagnosis, potentially leading to inadequate treatment and continued bleeding complications.