When should Serum Protein Electrophoresis (SPEP) be performed?

When to Perform Serum Protein Electrophoresis (SPEP)

SPEP should be performed when evaluating for monoclonal gammopathies, particularly in patients with unexplained anemia, renal insufficiency, hypercalcemia, bone lesions, or when multiple myeloma or related plasma cell disorders are suspected. 1

Primary Indications for SPEP

Clinical Presentations Requiring SPEP

• Unexplained:
  • Anemia
  • Renal insufficiency
  • Hypercalcemia
  • Bone lesions or unexplained bone pain
  • Elevated total protein with normal albumin
  • Proteinuria
  • Hypergammaglobulinemia
  • Immunodeficiency
  • Peripheral neuropathy of unknown etiology

Specific Diagnostic Scenarios

• Suspected plasma cell disorders:

  • Multiple myeloma
  • Monoclonal gammopathy of undetermined significance (MGUS)
  • Waldenstrom's macroglobulinemia
  • Solitary plasmacytoma
  • Amyloidosis 2

• Peripheral neuropathy evaluation:

  • SPEP with immunofixation should be considered in all patients with distal symmetric polyneuropathy, as it has one of the highest yields of abnormality in this setting 1

Risk-Based Approach to SPEP Testing

Initial Diagnostic Workup

For suspected plasma cell disorders, SPEP should be part of a comprehensive workup including:

• Complete blood count
• Serum creatinine and electrolytes
• Serum calcium
• Albumin
• Lactate dehydrogenase
• β2-microglobulin 1

Follow-Up Testing When SPEP is Positive

If a monoclonal protein is detected:

1. Quantify the M-protein
2. Perform serum immunofixation electrophoresis (SIFE)
3. Order serum free light chain assay
4. Obtain 24-hour urine for protein electrophoresis (UPEP) and immunofixation (UIFE) 2

Monitoring Recommendations Based on Diagnosis

MGUS Monitoring

• Low-risk MGUS (monoclonal protein <15 g/L, IgG type, normal FLC ratio):

  • Repeat SPEP in 6 months
  • If stable, follow every 2-3 years or when symptoms suggestive of plasma cell malignancy arise 1

• Intermediate/high-risk MGUS (monoclonal protein >15 g/L, IgA or IgM type, or abnormal FLC ratio):

  • Bone marrow examination at baseline
  • Follow with SPEP and CBC in 6 months
  • Then annually for life 1

Smoldering Multiple Myeloma

• Testing should be done 2-3 months after initial recognition
• If stable, follow every 4-6 months for 1 year
• Then every 6-12 months 1

Active Multiple Myeloma

• Quantitative immunoglobulins and M-protein quantitation at least every 3 months
• Other tests (CBC, renal function, calcium) as clinically indicated 1

Important Considerations and Pitfalls

Limitations of SPEP

• SPEP lacks sensitivity for detecting small monoclonal proteins
• Approximately 3% of multiple myeloma patients have no detectable M-proteins on SPEP (nonsecretory disease) 2
• SPEP has high negative predictive value (94%) but limited positive predictive value (47%) for plasma cell neoplasms in patients with lytic bone lesions 3

Complementary Testing

• When clinical suspicion remains high despite negative SPEP:
  • Serum free light chain assay
  • Serum immunofixation electrophoresis
  • 24-hour urine protein electrophoresis
  • Bone marrow examination 2

SPEP is an inexpensive, easy-to-perform screening procedure that provides valuable diagnostic information for detecting monoclonal gammopathies and should be included in the evaluation of suspected plasma cell disorders or when specific clinical presentations suggest these conditions.