Is multimer analysis indicated for this patient with a suspected inherited bleeding disorder, likely von Willebrand Disease (VWD)?

Multimer Analysis in Suspected von Willebrand Disease

Multimer analysis should not be performed as an initial screening test for von Willebrand Disease (VWD), but should only 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, 2

Initial Testing Algorithm for VWD

The appropriate initial laboratory evaluation for suspected VWD should include:

1. VWF antigen (VWF:Ag)
2. VWF ristocetin cofactor activity (VWF:RCo)
3. Factor VIII coagulant activity (FVIII:C)

These three tests are recommended by the NHLBI/NIH guidelines as the standard initial evaluation for VWD 1. They not only help establish the diagnosis but can also suggest the type and severity of VWD if present.

When to Perform Multimer Analysis

Multimer analysis should be performed only in the following circumstances:

• When one or more initial test results are abnormally low 1
• When the ratio of VWF:RCo to VWF:Ag is abnormally low (below 0.5–0.7) 1, 2
• When clinical information strongly suggests a high likelihood of abnormal VWF multimer analysis 1

Rationale for Limited Use of Multimer Analysis

There are several important reasons why multimer analysis is not recommended for initial screening:

• It is technically complex and qualitatively interpreted 1
• It has limited availability and slow turnaround time 1
• It lacks standardization across laboratories 1, 2
• It is more expensive and resource-intensive than initial screening tests 1

Clinical Importance of Proper Testing Sequence

Following the proper testing sequence is critical because:

• Correct VWD subtyping directly impacts treatment decisions 2
• Some treatments (like desmopressin) are contraindicated in certain VWD subtypes (e.g., Type 2B) 2
• Unnecessary multimer analysis increases healthcare costs without clinical benefit 1

Special Considerations

• In acquired von Willebrand syndrome (AVWS), particularly in conditions with high shear stress like aortic stenosis or ECMO support, sometimes only multimer analysis shows abnormalities with selective loss of high molecular weight multimers 1
• Newer semi-automated methods for multimer analysis (e.g., Hydragel 5 or 11 von Willebrand multimers test) may provide more standardized results with faster turnaround time 1, 2, 3

Pitfalls to Avoid

• Relying solely on bleeding time or platelet function analyzer (PFA-100) assays is not recommended due to conflicting data regarding sensitivity and specificity for VWD 1
• Interpretation of test results must consider variabilities contributed by patient conditions, blood sample handling, and laboratory methodology 1
• Consultation with a hemostasis specialist is recommended for further evaluation of suspected or diagnosed bleeding disorders 1

In summary, multimer analysis remains an important diagnostic tool for VWD subtyping but should be reserved for cases where initial testing indicates abnormalities or when specific clinical features strongly suggest certain VWD subtypes.