What is the next step for a mother and daughter with significant hemorrhaging and a von Willebrand's antigen to activity ratio of 0.7, indicating possible von Willebrand disease (VWD)?

Next Steps for Mother and Daughter with Suspected Von Willebrand Disease

The next step for this mother and daughter with significant hemorrhaging and a von Willebrand's antigen to activity ratio of 0.7 should be VWF multimer analysis to confirm and classify the type of von Willebrand disease (VWD). 1

Diagnostic Interpretation

The VWF activity to antigen ratio of 0.7 is at the borderline of what is considered abnormal according to current guidelines. The American Society of Hematology considers a ratio <0.7 as abnormal, indicating a qualitative defect in VWF 1. Given that:

• Both mother and daughter have experienced significant hemorrhaging
• Both have the same VWF antigen to activity ratio of 0.7
• The pattern suggests hereditary VWD (appearing in multiple family members)

This strongly points toward Type 2 VWD, which is characterized by qualitative defects in VWF.

Diagnostic Algorithm

1. VWF multimer analysis - This is the critical next step to:

   • Confirm the diagnosis of VWD
   • Classify the specific subtype (2A, 2B, 2M, or 2N)
   • Guide appropriate treatment selection

2. Additional specialized testing:

   • Ristocetin-Induced Platelet Aggregation (RIPA) test - Particularly helpful to distinguish Type 2B from other subtypes
   • VWF collagen binding assay (VWF:CB)
   • Factor VIII coagulant activity (FVIII:C)

3. Comprehensive bleeding assessment using a standardized bleeding assessment tool (BAT) to document the severity and pattern of bleeding symptoms

Subtype Classification

The VWF activity to antigen ratio of 0.7 suggests one of the Type 2 variants:

Subtype	Key Laboratory Findings	Clinical Implications
Type 2A	Loss of high & intermediate MW multimers	Poor response to desmopressin
Type 2B	Loss of high MW multimers, enhanced RIPA	Desmopressin contraindicated
Type 2M	Normal multimer pattern but decreased function	Variable response to desmopressin
Type 2N	Normal VWF:RCo/VWF:Ag ratio but reduced FVIII binding	Resembles mild hemophilia A

Treatment Planning

After confirming the subtype, treatment can be appropriately selected:

• For Type 2A and 2B: VWF-containing concentrates are the treatment of choice 1
• For Type 2M: A trial of desmopressin may be attempted first, but VWF concentrates may be needed 1
• For Type 2N: Factor VIII replacement may be required

Important Considerations

• Family screening: Since VWD is hereditary, screening of other first-degree relatives is recommended 1
• Avoid relying on a single test: The diagnosis of VWD requires multiple tests and clinical correlation 1
• Thrombotic risk: When treating with VWF concentrates, be aware of potential thrombotic complications, as seen in 3/10 patients in one study 2
• Treatment monitoring: For patients receiving VWF treatment, monitor serum sodium, bleeding time, factor VIII activity, ristocetin cofactor activity, and VWF antigen 1

Pitfalls to Avoid

1. Don't delay diagnosis due to borderline results - The combination of significant hemorrhaging and a ratio of 0.7 in two family members strongly suggests VWD
2. Don't start treatment without subtype classification - Different subtypes respond differently to treatments
3. Don't rely solely on RIPA test - It has limited sensitivity in Type 2 VWD 1
4. Don't overlook acquired causes - While hereditary VWD is likely in this family scenario, acquired causes should be excluded

The pattern of inheritance and identical VWF:RCo/VWF:Ag ratios in both mother and daughter strongly suggest hereditary VWD, making multimer analysis the most appropriate next step to guide treatment decisions.