Low-Dose Ristocetin-Induced Platelet Aggregation (RIPA) Test for Type 2 von Willebrand Disease
The low-dose RIPA test is particularly valuable for distinguishing Type 2B von Willebrand disease from other subtypes, as it typically shows enhanced platelet aggregation at low ristocetin concentrations in Type 2B patients. 1
Diagnostic Value of Low-Dose RIPA Test
The low-dose RIPA test works by evaluating the response of platelets to low concentrations of ristocetin in the presence of the patient's plasma. This test is especially useful for Type 2B VWD because:
- Type 2B VWD is characterized by an abnormally increased affinity of VWF for platelet glycoprotein Ib (GPIb) receptors
- This increased affinity results in enhanced platelet aggregation at low ristocetin concentrations
- Other VWD subtypes typically show normal or reduced responses at low ristocetin doses 1
Typical RIPA Characteristics by VWD Subtype:
| Subtype | RIPA Characteristics |
|---|---|
| Type 2A | May be normal at low-dose |
| Type 2B | Usually enhanced at low-dose, but can occasionally be normal |
| Type 2M | Often normal at low-dose |
| Type 2N | Resembles mild hemophilia A |
Comprehensive VWD Diagnostic Approach
The low-dose RIPA test should not be used in isolation but as part of a comprehensive diagnostic panel that includes:
Initial screening tests 2:
- VWF antigen (VWF:Ag)
- VWF ristocetin cofactor activity (VWF:RCo)
- Factor VIII coagulant activity (FVIII:C)
Additional specialized tests when initial results are abnormal:
- VWF multimer analysis (critical for subtyping)
- Low-dose RIPA test
- VWF collagen binding (VWF:CB)
- VWF:FVIII binding assay (for Type 2N)
Laboratory Findings in Type 2 VWD
Type 2 VWD is characterized by qualitative defects in VWF structure and function. Key laboratory findings include:
- VWF:RCo typically <30 IU/dL
- VWF:Ag often in the range of 30-200 IU/dL
- VWF:RCo/VWF:Ag ratio <0.5-0.7
- Specific multimer patterns vary by subtype 1
Important Considerations and Limitations
- The low-dose RIPA test has limited sensitivity in some Type 2 VWD cases 1
- Patient factors like stress, exercise, pregnancy, and inflammation can affect VWF levels and test results 1
- VWF multimer analysis is technically complex but essential for accurate subtyping 2
- No single laboratory test can definitively diagnose or exclude VWD 2, 3
Clinical Implications of Diagnosis
Accurate diagnosis and subtyping of VWD has important therapeutic implications:
- Desmopressin is generally contraindicated in Type 2B VWD as it can induce thrombocytopenia by releasing abnormal VWF multimers 1, 4
- Type 2B patients may experience intermittent thrombocytopenia that worsens during stress, infection, or pregnancy 5
- VWF-containing concentrates are the treatment of choice for Type 2B VWD 1, 4
Emerging Diagnostic Approaches
Newer methodologies are being developed to improve VWD diagnosis:
- Assays measuring VWF binding to recombinant GPIb without using platelets 3
- Genetic analysis can help clarify difficult cases where phenotypic classification is challenging 6
When clinical suspicion for Type 2 VWD is high but initial testing is inconclusive, specialized testing including the low-dose RIPA test and VWF multimer analysis should be performed at a center with expertise in VWD diagnosis.