Why would you order Serum Protein Electrophoresis (SPEP) for prioritization?

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Last updated: April 25, 2025View editorial policy

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From the Guidelines

I would order SPEP (Serum Protein Electrophoresis) to identify abnormal proteins in the blood, particularly when investigating conditions like multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), amyloidosis, or other plasma cell disorders. SPEP is most appropriate when patients present with symptoms such as unexplained bone pain, recurrent infections, fatigue, anemia, elevated total protein, hypercalcemia, or renal insufficiency. The test separates proteins in the blood based on their electrical charge, allowing for detection of monoclonal proteins (M-proteins) that appear as distinct spikes in the gamma region. When ordering SPEP, it's best to pair it with immunofixation electrophoresis (IFE) for better characterization of any abnormal proteins found. If SPEP shows an abnormal protein band, additional testing like free light chain assay, bone marrow biopsy, or imaging studies may be needed for complete evaluation. SPEP is valuable because it can detect early signs of plasma cell disorders before symptoms become severe, allowing for earlier intervention and potentially better outcomes, as supported by the guidelines outlined in 1.

Some key points to consider when ordering SPEP include:

  • The test is useful for detecting and monitoring monoclonal proteins in the blood, which can be indicative of plasma cell disorders.
  • SPEP should be paired with IFE for better characterization of abnormal proteins.
  • Additional testing may be needed to confirm the diagnosis and monitor disease progression.
  • The test can help identify patients at risk of progression to multiple myeloma or other plasma cell disorders, as discussed in 1 and 1.
  • SPEP is a valuable tool for early detection and intervention, potentially improving patient outcomes, as highlighted in 1, 1, and 1.

Overall, SPEP is a crucial diagnostic tool for identifying and monitoring plasma cell disorders, and its use should be guided by clinical judgment and evidence-based guidelines, such as those outlined in 1.

From the Research

Priorities for Ordering SPEP

The following are priorities for ordering Serum Protein Electrophoresis (SPEP):

  • Diagnosing multiple myeloma and other serum protein disorders 2
  • Evaluating radiolucent bone lesions of unknown etiology 3
  • Identifying patients with monoclonal gammopathies, which are associated with a clonal process that is malignant or potentially malignant 2
  • Ruling out multiple myeloma in patients with suspected disease, due to its high negative predictive value 3

Clinical Scenarios

SPEP is useful in the following clinical scenarios:

  • Initial evaluation of a radiolucent bone lesion of unknown etiology 3
  • Diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias 4
  • Monitoring of patients with multiple myeloma, as part of a panel of tests that includes serum protein electrophoresis, immunofixation electrophoresis, and free light chain quantitation 4

Test Characteristics

The characteristics of SPEP as a diagnostic test for multiple myeloma are:

  • Sensitivity: 71% 3
  • Specificity: 83% 3
  • Positive predictive value: 47% 3
  • Negative predictive value: 94% 3

Recommendations

SPEP is recommended to be performed:

  • In conjunction with urine electrophoresis, immunofixation electrophoresis, and free light chain assay 3
  • As part of a panel of tests for diagnosing and monitoring multiple myeloma 4
  • In patients with suspected multiple myeloma, to rule out the disease due to its high negative predictive value 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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