How to Order SPEP
Order serum protein electrophoresis (SPEP) as a single test through your laboratory system, typically alongside serum immunofixation and nephelometric quantification of immunoglobulins for comprehensive evaluation of suspected monoclonal gammopathies.
Ordering Protocol
When ordering SPEP for suspected plasma cell disorders or monoclonal gammopathies, the consensus guidelines recommend ordering it as part of a standardized panel 1:
Core Tests to Order Together:
- Serum protein electrophoresis (SPEP)
- Serum immunofixation - to confirm presence and type of monoclonal protein
- Nephelometric quantification of serum immunoglobulins (IgG, IgA, IgM)
- Serum-free light chain assay - adds significant diagnostic sensitivity 1, 2
The combination of SPEP plus free light chains achieves 95% sensitivity and 99% specificity for monoclonal gammopathies 3, making this pairing highly effective for screening.
Practical Ordering Details
What to Request from Your Laboratory:
Simply order "serum protein electrophoresis" or "SPEP" - this is a standard test available in most clinical laboratories. No special preparation is required from the patient (non-fasting sample acceptable).
Additional Concurrent Testing:
Based on the International Myeloma Workshop guidelines 1, also order:
- Complete blood count with differential
- Comprehensive metabolic panel (including calcium and creatinine)
- Serum β2-microglobulin and LDH
- 24-hour urine collection for urine protein electrophoresis and immunofixation (not a random urine sample - this is critical) 1
Critical Pitfalls to Avoid
Common Ordering Mistakes:
Don't order SPEP alone - The sensitivity of SPEP by itself is only 71% for plasma cell neoplasms 4. Always pair with immunofixation and free light chains for adequate diagnostic accuracy.
Don't substitute random urine for 24-hour collection - Guidelines explicitly state that random urine samples cannot replace 24-hour urine collection for electrophoresis 1. The 24-hour collection is essential for accurate quantification of urinary monoclonal protein.
Don't rely on SPEP for definitive diagnosis - SPEP has a positive predictive value of only 47% for plasma cell neoplasms presenting with lytic lesions 4, though its negative predictive value is 94%. Use it as a screening tool, not a standalone diagnostic test.
When SPEP Results May Be Misleading:
Small M-proteins (<1.5 g/dL): Significant imprecision occurs at low concentrations 5. Laboratories show greater variability when quantifying M-proteins below 1-2 g/dL.
Hypergammaglobulinemia background: Increased gamma globulin background leads to overestimation of M-protein, particularly with perpendicular drop gating methods 5.
Co-migration issues: M-proteins migrating in the middle of the gamma fraction are harder to quantify accurately than cathodal-migrating proteins 5.
Clinical Context for Ordering
Order SPEP when evaluating:
- Suspected multiple myeloma or plasma cell disorders
- Unexplained anemia, hypercalcemia, or renal insufficiency
- Lytic bone lesions of unknown etiology
- Elevated total protein on routine chemistry
- Screening for monoclonal gammopathy of undetermined significance (MGUS) 2
The test separates serum proteins based on electrical charge and size, creating a pattern that identifies monoclonal proteins as homogeneous peaks 1, 6.