Can Type 2 von Willebrand disease (VWD) be definitively ruled out in a patient with a normal low-dose Ristocetin-Induced Platelet Aggregation (RIPA) test and a von Willebrand factor (VWF) antigen activity level ratio of 0.7?

Type 2 von Willebrand Disease Cannot Be Definitively Ruled Out Based on Normal Low-Dose RIPA Test Alone

Type 2 von Willebrand disease (VWD) cannot be definitively ruled out in a patient with a von Willebrand factor (VWF) antigen activity level ratio of 0.7 and normal low-dose Ristocetin-Induced Platelet Aggregation (RIPA) test. While a normal low-dose RIPA test may suggest against Type 2B VWD, it does not exclude other Type 2 variants, particularly when the VWF:RCo/VWF:Ag ratio is borderline at 0.7.

Diagnostic Considerations for Type 2 VWD

VWF Activity/Antigen Ratio

• The VWF:RCo/VWF:Ag ratio of 0.7 is at the borderline cutoff value for distinguishing Type 1 from Type 2 VWD 1
• Guidelines recommend ratio cutoffs ranging from 0.5 to 0.7, with 0.7 commonly used 1
• A ratio of 0.7 does not definitively exclude Type 2 VWD variants

RIPA Test Limitations

• While enhanced low-dose RIPA is characteristic of Type 2B VWD, a normal RIPA result can still occur in some Type 2B patients 2
• Type 2A and 2M VWD may also present with normal low-dose RIPA results 2
• The RIPA test has limited sensitivity in diagnosing Type 2 VWD 2

Diagnostic Algorithm for Accurate VWD Subtyping

Required Additional Testing

1. VWF Multimer Analysis

   • Critical for confirming VWD diagnosis and classifying specific subtypes 2
   • Distinguishes between Type 2A, 2B, and 2M variants
   • Type 2A and 2B show loss of high molecular weight multimers
   • Type 2M shows normal multimer pattern despite functional discordance

2. Comprehensive VWF Activity Testing

   • Different VWF activity assays may reveal characteristic patterns:
     • Type 2M shows discordance between collagen binding vs. glycoprotein Ib binding assays 3
     • Type 2A shows decreased activity across multiple assays

3. Specialized Testing

   • VWF:GPIbM or VWF:GPIbR assays may help differentiate between VWD subtypes 4
   • These newer assays can distinguish between Type 2A and 2B VWD 4

Interpretation of Current Patient Data

• Platelet count of 155 is within normal range (not showing thrombocytopenia often seen in Type 2B)
• VWF:RCo/VWF:Ag ratio of 0.7 is borderline for Type 2 VWD
• Normal low-dose RIPA test does not exclude Type 2 variants, particularly:
  • Type 2A may show normal RIPA at low-dose 2
  • Type 2M often presents with normal low-dose RIPA 2
  • Some Type 2B patients can have normal RIPA results 2

Common Pitfalls in VWD Diagnosis

• Relying on single tests: No single test can definitively rule out Type 2 VWD; comprehensive testing is required
• Misinterpreting borderline ratios: A ratio of 0.7 is at the cutoff and should prompt further investigation
• Overlooking test variability: Patient factors like stress, exercise, and inflammation can affect VWF levels and test results 2
• Misdiagnosing Type 2M: Type 2M VWD is frequently misdiagnosed as Type 2A or Type 1 VWD 3

Conclusion for This Patient

Given the borderline VWF:RCo/VWF:Ag ratio of 0.7 and the known limitations of the RIPA test, additional testing is required before Type 2 VWD can be ruled out:

1. VWF multimer analysis is essential
2. Additional specialized VWF activity assays should be performed
3. Genetic testing may be considered for definitive diagnosis

A normal low-dose RIPA test alone is insufficient to exclude Type 2 VWD variants, particularly when other parameters are borderline.