What are the diagnostic criteria for type 2B von Willebrand's disease?

Diagnostic Criteria for Type 2B von Willebrand Disease

Type 2B von Willebrand disease is diagnosed by demonstrating increased VWF affinity for platelet GP Ib, often with decreased platelet numbers, VWF:RCo levels <30 IU/dL, VWF:Ag levels <30-200 IU/dL, normal or decreased FVIII, and a VWF:RCo/VWF:Ag ratio usually <0.5-0.7. 1

Laboratory Parameters

The diagnosis of Type 2B VWD requires specific laboratory findings:

• VWF:RCo (ristocetin cofactor activity): <30 IU/dL
• VWF:Ag (antigen): <30-200 IU/dL
• FVIII activity: Normal or decreased
• VWF:RCo/VWF:Ag ratio: Usually <0.5-0.7
• Platelet count: Often decreased (thrombocytopenia)
• Multimer analysis: Typically shows loss of high molecular weight VWF multimers 1

Functional Testing

The hallmark functional abnormality in Type 2B VWD is:

• Increased VWF affinity for platelet GP Ib receptors 1
• Enhanced ristocetin-induced platelet aggregation (RIPA) at low concentrations of ristocetin 2

Important Diagnostic Considerations

1. Thrombocytopenia:

   • Present in many but not all patients
   • Can be exacerbated by physiologic stressors like pregnancy 2
   • Serves as an important diagnostic clue when present

2. Multimer Pattern Variations:

   • Some patients (approximately one-third) may have a normal multimer pattern despite having Type 2B VWD 3
   • Patients without large multimers typically have more severe bleeding scores 3

3. RIPA Testing Caution:

   • A negative RIPA at 0.5 mg/mL does not necessarily rule out Type 2B VWD 4
   • Some mutations (like p.R1308C) can present with absent RIPA at standard testing concentrations

4. Genetic Testing:

   • Identification of mutations in the A1 domain of VWF is confirmatory 2
   • Common mutations include p.V1316M, p.R1308C, and p.S1310F 4

Diagnostic Pitfalls to Avoid

1. Relying solely on VWF:RCo/VWF:Ag ratio:

   • Some Type 2B patients (particularly those with p.S1310F mutation) may have normal VWF:RCo/VWF:Ag ratios 4

2. Missing intermittent thrombocytopenia:

   • Platelet counts may fluctuate and should be checked repeatedly 5

3. Failing to test family members:

   • Type 2B VWD has autosomal dominant inheritance
   • Family studies are important for complete diagnostic profiles 4

4. Confusing with other VWD subtypes:

   • Type 2A and 2M can have similar laboratory findings
   • Specific testing for increased platelet binding is essential for Type 2B diagnosis 1

Diagnostic Algorithm

1. Initial screening:

   • Complete blood count (check for thrombocytopenia)
   • VWF:Ag, VWF:RCo, FVIII activity
   • Calculate VWF:RCo/VWF:Ag ratio

2. If suspicious for Type 2B:

   • Perform RIPA at low concentrations of ristocetin
   • Analyze VWF multimer distribution
   • Consider genetic testing for mutations in the A1 domain of VWF

3. Confirm diagnosis when finding:

   • Enhanced VWF binding to platelets
   • VWF:RCo <30 IU/dL
   • VWF:RCo/VWF:Ag ratio usually <0.5-0.7
   • With or without thrombocytopenia
   • With or without loss of high molecular weight multimers

Remember that Type 2B VWD represents fewer than 5% of all VWD cases but requires specific identification due to its unique management considerations 6.