How do you rule out type 2B von Willebrand disease (VWD) in this patient?

Ruling Out Type 2B von Willebrand Disease

To rule out type 2B von Willebrand disease (VWD), multimer analysis combined with ristocetin-induced platelet aggregation (RIPA) testing is essential, as these are the definitive tests that distinguish type 2B from other VWD subtypes. 1

Key Laboratory Tests to Rule Out Type 2B VWD

1. Initial Screening Tests:

   • VWF antigen (VWF:Ag)
   • VWF activity (VWF:RCo)
   • VWF:RCo/VWF:Ag ratio
   • Factor VIII level
   • Complete blood count (CBC) with platelet count

2. Specific Tests to Rule Out Type 2B:

   • Ristocetin-Induced Platelet Aggregation (RIPA):

     • Type 2B shows enhanced RIPA at low concentrations of ristocetin
     • This is the critical distinguishing test for type 2B 1, 2

   • VWF Multimer Analysis:

     • Type 2B shows loss of high molecular weight multimers
     • Type 2A also shows loss of high and intermediate multimers
     • Type 2M shows normal multimer pattern 1

   • Platelet Count:

     • Type 2B often shows thrombocytopenia, especially after DDAVP challenge
     • This can help distinguish from other VWD types 1, 3

Diagnostic Algorithm for Ruling Out Type 2B VWD

1. Step 1: Assess VWF:RCo/VWF:Ag ratio

   • If ratio is <0.5-0.7, suspect Type 2 VWD (could be 2A, 2B, or 2M) 1
   • If ratio is >0.7, Type 2B is unlikely

2. Step 2: Perform RIPA test

   • Enhanced RIPA at low concentrations → Type 2B likely
   • Normal RIPA → Type 2B unlikely 1, 2

3. Step 3: Examine multimer pattern

   • Loss of high molecular weight multimers + enhanced RIPA → Type 2B confirmed
   • Loss of high and intermediate multimers + normal RIPA → Type 2A
   • Normal multimer pattern + low VWF:RCo/VWF:Ag ratio → Type 2M 1, 4

4. Step 4: Observe platelet count

   • Thrombocytopenia (especially after DDAVP challenge) + enhanced RIPA → strongly supports Type 2B 3, 5

Important Clinical Considerations

• Type 2B VWD is often misdiagnosed as Type 2A due to similar multimer patterns, but RIPA testing can differentiate between them 2

• DDAVP challenge can be diagnostic:

  • In Type 2B, DDAVP often causes thrombocytopenia
  • This response is characteristic of Type 2B and can help confirm diagnosis 3, 5
  • DDAVP is contraindicated for treatment in Type 2B due to risk of thrombosis 6

• Genetic testing can be valuable when laboratory results are inconclusive:

  • Type 2B mutations are located in the A1 domain of VWF
  • Genetic testing can confirm diagnosis in complex cases 4, 7

Potential Pitfalls to Avoid

• Don't rely solely on VWF:RCo/VWF:Ag ratio for diagnosis, as both Type 2A and 2B can have similar ratios 1, 2

• Don't overlook RIPA testing - it's the key differentiating test for Type 2B 1

• Don't misinterpret thrombocytopenia as immune thrombocytopenia when it could be Type 2B VWD 3

• Don't administer DDAVP for treatment of Type 2B patients as it can worsen thrombocytopenia and is contraindicated 6

• Be aware that some "atypical" Type 2B variants may present with normal multimer patterns but still show enhanced RIPA 5