What should I do if the hematopathologist (blood disease specialist) refuses to run a multimer test for a patient with suspected von Willebrand disease (VWD)?

Managing a Hematopathologist's Refusal to Run a Multimer Test in Suspected von Willebrand Disease

If the hematopathologist refuses to run a multimer test for your patient with suspected von Willebrand disease (VWD), you should refer the patient to a hemophilia treatment center or a hematologist with expertise in bleeding disorders for definitive diagnosis and appropriate testing. 1

Understanding When Multimer Testing is Needed

Multimer analysis is a specialized test that should be performed in specific situations:

• When initial VWD testing shows abnormal results (e.g., abnormally low VWF:RCo or ratio of VWF:RCo to VWF:Ag <0.5-0.7) 2
• When clinical information strongly suggests VWD despite normal initial testing 2
• When subtyping of VWD is necessary to guide treatment decisions, particularly for distinguishing between Type 2A and 2B VWD 1

Steps to Take When Multimer Testing is Refused

1. Review existing test results:

   • Check if you have complete initial VWD testing (VWF:Ag, VWF:RCo, and FVIII) 1
   • Calculate the VWF:RCo/VWF:Ag ratio (ratio <0.5-0.7 suggests Type 2 VWD) 1

2. Consider alternative testing approaches:

   • Request newer assays with improved performance for diagnosing VWD:
     • VWF:GPIbR
     • VWF:GPIbM
     • VWF:Ab 1
   • Request Ristocetin-Induced Platelet Aggregation (RIPA) test, which can help distinguish Type 2B from other subtypes 1

3. Seek specialized consultation:

   • Refer to a hemophilia treatment center with laboratory capabilities for specialized VWD testing 3
   • Consult with a hematologist experienced in bleeding disorders 1

4. Document the clinical necessity:

   • Provide detailed documentation of bleeding symptoms
   • Explain why proper subtyping is essential for treatment decisions
   • Note that different VWD subtypes respond differently to treatments (e.g., Type 2M may respond to desmopressin while Type 2A often requires VWF-containing concentrates) 1

Clinical Implications of Not Obtaining Multimer Analysis

Without multimer analysis, several clinical risks exist:

• Misdiagnosis or incomplete diagnosis: Inability to properly subtype VWD can lead to inappropriate treatment approaches 1
• Treatment complications: Type 2B VWD patients may experience thrombocytopenia if treated with desmopressin, which is contraindicated in this subtype 1
• Inadequate bleeding prevention: Without proper subtyping, patients may receive suboptimal prophylaxis before procedures or during bleeding episodes 1

Alternative Diagnostic Approaches

If multimer testing remains unavailable:

• Genetic testing: Consider VWF gene sequencing, which can identify specific mutations associated with different VWD subtypes 4
• Functional assays: Use a combination of VWF:RCo/VWF:Ag ratio and RIPA to make presumptive subtype diagnosis 1
• Therapeutic trial: In urgent situations, a carefully monitored therapeutic trial with desmopressin may help determine response, though this approach carries risks 5

Key Pitfalls to Avoid

• Don't rely on a single test for VWD diagnosis; multiple tests and clinical correlation are required 1
• Don't ignore borderline results; mild VWD may present with borderline laboratory values but still cause significant bleeding 1
• Don't overlook pre-analytical variables such as sample collection, processing, and storage that can affect test results 1
• Don't proceed with invasive procedures without proper diagnosis and treatment planning for patients with suspected VWD 3

Remember that proper diagnosis and subtyping of VWD is essential for appropriate treatment selection and preventing bleeding complications. If local resources are insufficient, referral to a specialized center is the best approach to ensure optimal patient care.