Von Willebrand Disease Diagnostic Testing
The next diagnostic test for this patient should be VWF multimer analysis to determine the specific subtype of Type 2 von Willebrand Disease. 1
Diagnostic Interpretation of Current Findings
Based on the information provided:
- Patient has VWF antigen level of 1.33 (likely 133% of normal)
- Both patient and mother have VWF antigen to activity ratio of 0.7
These findings strongly suggest Type 2 von Willebrand Disease (VWD):
- A VWF:RCo/VWF:Ag ratio ≤0.7 is diagnostic for Type 2 VWD according to current guidelines 1, 2
- The normal or elevated VWF antigen level (1.33) with decreased activity ratio indicates a qualitative defect in VWF function rather than a quantitative deficiency
Diagnostic Algorithm for Type 2 VWD Subtyping
VWF Multimer Analysis - This is the critical next step
Based on multimer results, additional testing may include:
- Ristocetin-Induced Platelet Aggregation (RIPA) - Particularly useful for Type 2B
- VWF:FVIII binding assay - If Type 2N is suspected
Expected Multimer Patterns by Subtype
| Subtype | Multimer Pattern | Clinical Implications |
|---|---|---|
| Type 2A | Loss of high & intermediate MW multimers | Poor response to DDAVP |
| Type 2B | Loss of high MW multimers only | DDAVP contraindicated |
| Type 2M | Normal multimer pattern | Variable DDAVP response |
| Type 2N | Normal multimer pattern | Resembles mild hemophilia A |
Rationale for Multimer Analysis
Multimer analysis is superior to other tests for several reasons:
- The American Society of Hematology specifically recommends multimer analysis for subtyping Type 2 VWD 1
- RIPA testing alone can yield false normal results even in Type 2B VWD 1
- Multimer analysis provides critical information about the structural integrity of VWF that directly impacts treatment decisions 4
- Modern multimer analysis techniques offer high sensitivity and can detect VWF abnormalities at levels as low as 1.6 IU/dL 5
Technical Considerations
- Both low-resolution and high-resolution electrophoretic techniques may be needed:
- Low-resolution differentiates Type 1 from Type 2 and some subtypes
- High-resolution techniques are required to differentiate between Type 2B, 2C, and 2D 6
- In-gel immunostaining with infrared fluorescent imaging offers superior sensitivity and resolution compared to traditional methods 5
Clinical Implications
Proper subtyping through multimer analysis has direct treatment implications:
- Type 2A often requires VWF-containing concentrates rather than DDAVP
- Type 2B has DDAVP contraindicated due to risk of thrombocytopenia
- Type 2M may respond to DDAVP
- Type 2N requires specific factor replacement strategies 1, 4
The family history (mother with similar findings) supports the hereditary nature of this condition, consistent with the autosomal dominant inheritance pattern seen in most Type 2 VWD subtypes.