Should a multimer test be done to rule out Type 2B von Willebrand's disease (VWD)?

Multimer Testing for Type 2B von Willebrand Disease

Multimer analysis should not be performed as an initial screening test for Type 2B von Willebrand Disease (VWD), but should be ordered after initial VWD testing identifies abnormal results such as low VWF:RCo or low VWF:RCo/VWF:Ag ratio (<0.5-0.7). 1

Diagnostic Algorithm for Type 2B VWD

Initial Testing

1. Complete blood count (CBC) - may show thrombocytopenia in Type 2B
2. Prothrombin time (PT)
3. Activated partial thromboplastin time (PTT)
4. Initial VWD panel:
   • VWF antigen (VWF:Ag)
   • VWF ristocetin cofactor activity (VWF:RCo)
   • Factor VIII coagulant activity (FVIII)

When to Order Multimer Analysis

Multimer analysis should be ordered when:

• Initial VWD testing shows abnormal results (e.g., low VWF:RCo or VWF:RCo/VWF:Ag ratio <0.5-0.7)
• Clinical information strongly suggests Type 2 VWD
• Ristocetin-induced platelet aggregation (RIPA) shows increased response at low ristocetin concentrations (characteristic of Type 2B)

Differentiating Type 2B from Other VWD Types

Type 2B VWD has specific laboratory characteristics that distinguish it from other types:

• VWF:RCo typically <30 IU/dL
• VWF:Ag usually <30-200 IU/dL
• VWF:RCo/VWF:Ag ratio generally <0.5-0.7
• Selective deficiency of high-molecular-weight multimers on multimer analysis
• Increased RIPA at low ristocetin concentrations - this is the key distinguishing feature of Type 2B 2
• Often presents with mild to moderate thrombocytopenia

Clinical Implications

Correctly identifying Type 2B VWD is critical because:

1. Desmopressin (DDAVP) is contraindicated in Type 2B VWD as it may cause thrombocytopenia and increased risk of thrombosis 3, 4
2. Type 2B patients may require different treatment approaches than other VWD types
3. Type 2B VWD can present with variable clinical manifestations even within the same family 5

Common Pitfalls in Diagnosis

• Misdiagnosing Type 2B as Type 2A or Type 1 VWD due to incomplete testing 6
• Relying solely on VWF:Ag and VWF:RCo without RIPA testing
• Failing to consider Type 2B when thrombocytopenia is present
• Not recognizing that clinical manifestations can vary significantly even with identical mutations 7

Technical Considerations for Multimer Analysis

Multimer analysis is technically complex and has limitations:

• Qualitatively interpreted in conjunction with other test results
• Limited availability and slow turnaround time 1
• Requires specialized laboratory expertise
• Lacks standardization across laboratories 1

Newer semi-automated methods (e.g., Hydragel 5 or 11 von Willebrand multimers test) may provide more standardized results with faster turnaround time 1.

In summary, while multimer analysis is valuable for confirming and classifying VWD subtypes, it should be ordered as a second-line test after initial VWD screening tests indicate a potential Type 2 variant, particularly when clinical features or RIPA testing suggest Type 2B VWD.