Can a normal RIPA (Ristocetin-Induced Platelet Aggregation) test be used to totally rule out von Willebrand disease in this family?

Normal RIPA Test Cannot Fully Rule Out Von Willebrand Disease in This Family

A normal Ristocetin-Induced Platelet Aggregation (RIPA) test alone cannot be used to completely rule out von Willebrand disease (VWD) in this family, especially given the mother's elevated bleeding assessment tool score of 12 and borderline VWF antigen activity ratio of 0.69.

Diagnostic Considerations for VWD

Clinical and Laboratory Assessment

• The mother presents with:
  • Bleeding assessment tool score of 12 (significantly elevated)
  • VWF antigen activity ratio of 0.69 (borderline low)
  • Platelet count of 155 (within normal range, though history of counts between 120-150)
  • Normal RIPA test

Limitations of RIPA Testing

• According to the 2008 NHLBI/NIH guidelines, no single laboratory test can definitively screen for VWD 1
• RIPA test characteristics vary by VWD subtype:
  • Type 2M VWD often shows normal RIPA at low doses despite having VWD 2
  • Some variants of VWD can present with normal RIPA results but still have clinically significant disease 3, 4
  • RIPA primarily helps distinguish Type 2B from other types rather than rule out VWD entirely 5

Proper Diagnostic Algorithm

1. Initial assessment: The elevated bleeding score (12) already suggests significant bleeding tendency

2. First-line laboratory tests should include:

   • VWF antigen (VWF:Ag)
   • VWF ristocetin cofactor activity (VWF:RCo)
   • Factor VIII coagulant activity (FVIII)
   • Complete blood count with platelet count
   • aPTT 2

3. Interpretation of VWF:RCo/VWF:Ag ratio:

   • The mother's ratio of 0.69 is borderline low (cutoff typically <0.5-0.7) 1
   • This borderline result requires careful interpretation in context of clinical findings

Clinical Implications

Why RIPA Cannot Rule Out VWD in This Case

• The mother's elevated bleeding score (12) strongly suggests a bleeding disorder
• VWF antigen activity ratio of 0.69 is borderline and may indicate mild VWD
• Certain VWD variants (particularly Type 2M) can present with normal RIPA results 2, 5
• Family history is significant, suggesting inherited bleeding disorder

Recommended Next Steps

• Complete the full diagnostic panel for VWD including:
  • VWF multimer analysis to assess distribution of VWF multimers
  • Consider VWF collagen binding assay (VWF:CB) which may detect abnormalities when RIPA is normal 5
  • Genetic testing may be warranted given the family history 5

Common Pitfalls to Avoid

• Relying on a single normal test (RIPA) to rule out VWD
• Failing to correlate laboratory findings with clinical bleeding history
• Not considering VWD variants that may present with normal RIPA
• Overlooking the significance of a borderline VWF:RCo/VWF:Ag ratio (0.69)

The diagnosis of VWD requires synthesis of clinical assessment (personal and family history of bleeding) and comprehensive laboratory testing 1. Given the mother's elevated bleeding score and borderline VWF ratio, further specialized VWD testing is warranted despite the normal RIPA result.