Would you still order VWF (von Willebrand factor) multimer testing with a normal RIPA (ristocetin-induced platelet aggregation) test at low doses?

VWF Multimer Testing in the Setting of Normal RIPA at Low Doses

No, VWF multimer testing is not indicated when RIPA testing is normal at low doses, especially with a platelet count of 155. According to the 2008 NHLBI/NIH guidelines, VWF multimer analysis should only be performed if initial VWD testing identifies an abnormal result or if clinical information suggests a high likelihood of abnormal VWF multimer analysis 1.

Diagnostic Algorithm for VWD

The recommended diagnostic approach follows this sequence:

1. Initial VWD tests (all three recommended):

   • VWF antigen (VWF:Ag)
   • VWF ristocetin cofactor activity (VWF:RCo)
   • Factor VIII coagulant activity (FVIII)

2. Specialized testing (only if indicated):

   • VWF multimer analysis should be ordered only when:
     • One or more initial test results are abnormally low
     • The ratio of VWF:RCo to VWF:Ag is abnormally low (below 0.5-0.7)
     • Clinical information strongly suggests VWD despite normal initial tests

Interpretation of Normal RIPA at Low Doses

A normal RIPA test at low doses indicates:

• Adequate functional interaction between VWF and platelets
• Sufficient high molecular weight multimers are likely present
• The platelet count of 155 is within normal range, supporting adequate platelet function

Clinical Reasoning

The decision not to proceed with VWF multimer testing is based on:

1. Test sequencing logic: Multimer analysis is technically complex and qualitative, intended for subtyping rather than screening 1.

2. Resource utilization: Multimer analysis is labor-intensive and should be reserved for cases with abnormal initial testing.

3. Diagnostic yield: With normal RIPA at low doses, the likelihood of finding clinically significant multimer abnormalities is low.

Special Considerations

• Type 2M VWD: This variant shows decreased VWF-dependent platelet adhesion without selective deficiency of high-molecular-weight multimers, with a VWF:RCo/VWF:Ag ratio typically <0.5-0.7 2. If this is suspected clinically despite normal RIPA, further testing might be warranted.

• Acquired VWD: In certain conditions (like ECMO or aortic stenosis), sometimes only VWF multimer analysis is abnormal, with mild reduction or loss of the highest molecular weight multimers 1. However, these cases typically show abnormal RIPA or other initial test abnormalities.

Potential Pitfalls

• False normal RIPA: Ensure RIPA testing was performed correctly, as technical factors can affect results.

• Borderline results: If RIPA results were borderline normal, consider the complete clinical picture.

• Timing of testing: VWF is an acute phase reactant; testing during stress or inflammation may mask underlying deficiencies.

By following this evidence-based approach, you can avoid unnecessary testing while ensuring appropriate diagnosis of VWD when clinically indicated.