Why would it not be prudent to do the multimer test in a patient with a history of hemorrhages, a family history of severe bleeding, and a von Willebrand's antigen activity ratio of 0.7?

Multimer Testing is Essential in This Case with Strong Clinical Suspicion of von Willebrand Disease

Multimer testing is absolutely indicated in this patient with a VWF antigen activity ratio of 0.7, history of four hemorrhages including two delayed post-surgical bleeds, and family history of severe bleeding in both mother and uncle.

Diagnostic Rationale

The clinical presentation strongly suggests von Willebrand disease (VWD) despite borderline initial testing results:

• VWF antigen activity ratio of 0.7 is at the threshold for suspecting type 2 VWD 1
• History of four hemorrhages, including two delayed post-surgical bleeds
• Strong family history with both mother and uncle having severe bleeding
• RIPA test may have false normal results

Diagnostic Algorithm for This Case

1. Initial testing results: VWF:RCo/VWF:Ag ratio of 0.7 is at the critical threshold that warrants further investigation
2. Clinical bleeding history: Multiple hemorrhages and family history significantly increase pre-test probability
3. Next appropriate step: Multimer analysis to detect potential qualitative VWF defects

Evidence Supporting Multimer Testing

The NHLBI VWD Guidelines explicitly state that multimer analysis should be performed "if initial VWD testing identifies an abnormal result (e.g., abnormally low VWF:RCo or ratio of VWF:RCo to VWF:Ag) or clinical information suggests a high likelihood of abnormal VWF multimer analysis" 1.

This patient meets both criteria:

• Borderline ratio of 0.7 (threshold value)
• Strong clinical history highly suggestive of VWD

Limitations of Initial Testing

Standard VWD testing has significant limitations:

• A study of acquired von Willebrand syndrome found that VWF:RCo/Ag ratio <0.7 had only 26% sensitivity 2
• VWF:CB/Ag ratio <0.7 had only 46% sensitivity 2
• Even a combination of VWF:Ag <50 IU/dL, VWF:RCo/Ag ratio <0.7, and VWF:CB/Ag ratio <0.8 achieved only 86% sensitivity 2
• The same study emphasized "the importance of multimer analysis in all patients with suspected AVWS" 2

Clinical Implications of Missing the Diagnosis

Failing to perform multimer analysis could lead to:

1. Missed diagnosis of type 2 VWD, particularly in borderline cases
2. Inappropriate treatment selection (especially important as desmopressin is contraindicated in Type 2B VWD) 3
3. Continued risk of serious bleeding events, including surgical complications

Management Considerations

If multimer analysis confirms type 2 VWD:

• Treatment approach will differ from type 1 VWD
• VWF-containing concentrates may be required instead of desmopressin 3
• Family testing would be indicated to identify inheritance patterns

Conclusion

The combination of borderline VWF:RCo/VWF:Ag ratio (0.7) with significant personal and family bleeding history creates a high pre-test probability for type 2 VWD that requires multimer analysis for definitive diagnosis. Given the potential serious consequences of missed diagnosis and the clear clinical indications, multimer testing is not only prudent but essential in this case.