What is the sensitivity of a RIPA (Ristocetin-Induced Platelet Aggregation) test for diagnosing Type 2B von Willebrand disease with a normal platelet count, and is there a risk of false normal results?

Sensitivity of RIPA Test in Type 2B von Willebrand Disease with Normal Platelet Count

The RIPA test has limited sensitivity for diagnosing Type 2B von Willebrand disease when performed once on a patient with a normal platelet count of 155, and there is a significant risk of false normal results. 1

Limitations of RIPA Testing in Type 2B VWD

The ristocetin-induced platelet aggregation (RIPA) test is a key diagnostic tool for Type 2B von Willebrand disease, but it has important limitations:

• RIPA may be negative at standard ristocetin concentrations (0.5 mg/mL) in up to 75% of patients with certain Type 2B VWD mutations, particularly those with the p.R1308C mutation 2
• Normal platelet counts can further decrease sensitivity, as thrombocytopenia is often a characteristic feature of Type 2B VWD that enhances test accuracy 1, 3
• A single RIPA test may miss the diagnosis, especially in patients with borderline or normal platelet counts 4

Diagnostic Approach for Suspected Type 2B VWD

For accurate diagnosis when Type 2B VWD is suspected:

1. Complete VWF panel is essential:

   • VWF:RCo/VWF:Ag ratio (typically <0.5-0.7 in Type 2B)
   • VWF multimer analysis (shows loss of high molecular weight multimers)
   • RIPA at multiple low ristocetin concentrations (0.3-0.5 mg/mL)

2. Consider additional testing:

   • RIPA mixing tests with normal platelets
   • Cryoprecipitate challenge test
   • Genetic testing of VWF gene (exon 28) 5, 3

Important Clinical Considerations

• Type 2B VWD can present with normal platelet counts in some cases, making diagnosis more challenging 1, 3
• The VWF:RCo/VWF:Ag ratio may be normal in some Type 2B variants, particularly with the p.S1310F mutation 2
• Family history is crucial - 98% of clinicians include it in their initial bleeding assessment 1
• Phenotypic heterogeneity exists even within families carrying the same mutation 4

Pitfalls to Avoid

• Do not rule out Type 2B VWD based on a single negative RIPA test, especially with normal platelet counts 2
• Do not rely solely on VWF:RCo/VWF:Ag ratio - some Type 2B variants can have normal ratios 2
• Do not overlook the need for multimer analysis - this is essential for proper subtyping 1, 6
• Be aware that RIPA sensitivity varies by specific mutation - some mutations (like p.R1308C) frequently show negative RIPA at standard concentrations 2

Recommendation for Accurate Diagnosis

For a patient with a normal platelet count of 155 and suspected Type 2B VWD:

1. Perform RIPA at multiple low ristocetin concentrations (0.3,0.4, and 0.5 mg/mL)
2. Complete full VWF panel including multimer analysis
3. Consider genetic testing of VWF gene exon 28 if clinical suspicion remains high despite negative RIPA
4. Evaluate first-degree relatives, as VWD is hereditary with high penetrance 1, 2