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Diagnostic Tests: Serum Protein Electrophoresis (SPEP)

Overview — What SPEP Is?

Serum protein electrophoresis (SPEP) is a laboratory test that separates and quantifies the major protein components of the blood. By applying an electric current to serum, proteins migrate based on their size and charge, producing a pattern that distinguishes:


  • Albumin
  • α1, α2, β, and γ globulin fractions
  • Immunoglobulins (IgG, IgA, IgM, etc.)

This allows clinicians to identify abnormal elevations—especially monoclonal spikes (“M-spikes”) that suggest plasma cell disorders.

When SPEP Is the Correct Answer

Choose SPEP when evaluating:


  • Elevated total serum protein
  • Unexplained anemia, especially with rouleaux formation
  • Bone pain or lytic lesions on X-ray
  • Renal failure of unclear origin
  • Symptoms suggestive of plasma cell dyscrasias (fatigue, weight loss, recurrent infections)

SPEP is the best initial test to diagnose multiple myeloma, particularly when:


  • X-rays for lytic lesions have already been performed
  • Or when imaging is not an available answer choice
It can also help evaluate for Waldenström macroglobulinemia and other gammopathies.

Most Common Reason for an Abnormal SPEP

The most common cause of an abnormal SPEP—particularly a monoclonal spike—is:

Monoclonal Gammopathy of Unknown/Undetermined Significance (MGUS)

MGUS is far more common than multiple myeloma and is often asymptomatic, although it requires monitoring due to its risk of progression.


Most Accurate Diagnostic Test

For confirming an IgG monoclonal abnormality detected on SPEP, the most accurate test is:

Bone Marrow Biopsy

Findings diagnostic of multiple myeloma include:
  • >10% clonal plasma cells
  • Evidence of organ damage (CRAB criteria: hyperCalcemia, Renal failure, Anemia, Bone lesions)
For Waldenström macroglobulinemia, SPEP will show an IgM spike, and marrow biopsy will show lymphoplasmacytic cells.

If you’d like, I can produce a quick comparison table: SPEP vs. UPEP vs. Immunofixation, or a high-yield myeloma diagnostic algorithm.




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