What other tests should be done when testing Serum Protein Electrophoresis (SPEP)?

Complementary Tests to Perform with Serum Protein Electrophoresis (SPEP)

When performing serum protein electrophoresis (SPEP), several additional tests should be ordered simultaneously to ensure comprehensive evaluation for plasma cell disorders, including serum free light chain assay, serum immunofixation electrophoresis, and 24-hour urine studies. 1

Essential Complementary Tests

Blood Tests:

• Complete blood count (CBC) with differential and platelet count
• Serum chemistry panel including:
  • Creatinine
  • Albumin
  • Calcium (corrected)
  • Lactate dehydrogenase (LDH) as clinically indicated
  • Beta-2 microglobulin as clinically indicated
• Serum quantitative immunoglobulins (IgG, IgA, IgM)
• Serum immunofixation electrophoresis (SIFE)
• Serum free light chain (FLC) assay 1, 2

Urine Tests:

• 24-hour urine collection for:
  • Total protein
  • Urine protein electrophoresis (UPEP)
  • Urine immunofixation electrophoresis (UIFE) 1

Rationale for Complementary Testing

The combination of SPEP with serum free light chain assay has been shown to have 100% sensitivity for detecting plasma cell disorders, significantly outperforming SPEP alone (which has only 71% sensitivity) 3, 4. This comprehensive approach is particularly important because:

1. Approximately 3% of multiple myeloma patients have nonsecretory disease with no detectable M-proteins on SPEP 2
2. Small M-proteins may be missed by SPEP alone 2
3. Light chain disease may be detected by FLC assay when SPEP is negative 4

Clinical Algorithm for SPEP Testing

1. Initial Testing Panel:

   • SPEP with quantification of protein fractions
   • Serum free light chain assay
   • Serum immunofixation electrophoresis
   • Quantitative immunoglobulins
   • 24-hour urine for UPEP and UIFE 1, 2

2. If Monoclonal Protein Detected:

   • Bone marrow aspirate and biopsy
   • Imaging studies (MRI, CT, or PET/CT) as clinically indicated 1

3. If Initial Tests Negative but Clinical Suspicion Remains High:

   • Ensure serum free light chain assay has been performed
   • Consider bone marrow examination 2, 4

Common Pitfalls to Avoid

• Relying solely on SPEP: SPEP lacks adequate sensitivity (71%) and positive predictive value (47%) to provide a definitive diagnosis of myeloma in patients with lytic bone lesions 3
• Omitting urine studies: Some monoclonal proteins may be excreted primarily in urine 2
• Missing light chain disease: Serum free light chain analysis is essential for detecting light chain disorders that may be missed by SPEP 4, 5
• Inconsistent methodology: Using consistent testing methods is crucial for accurate serial monitoring 2

Follow-up Testing Frequency

• For solitary plasmacytoma: Every 3-6 months
• For smoldering myeloma: Every 3-6 months
• For MGUS: Based on risk stratification (low-risk: repeat in 6 months, then every 2-3 years if stable; intermediate/high-risk: follow-up every 6-12 months) 1, 2

By implementing this comprehensive testing approach, clinicians can maximize diagnostic accuracy and ensure appropriate management of patients with suspected plasma cell disorders, ultimately improving morbidity, mortality, and quality of life outcomes.