Testing for Erythropoietin (EPO)
Serum erythropoietin measurement is generally not indicated in most clinical situations, particularly in chronic kidney disease where EPO deficiency is the presumed cause of anemia when serum creatinine is ≥2 mg/dL. 1
When EPO Testing is NOT Recommended
In chronic kidney disease (CKD) patients: If no other cause for anemia is detected and serum creatinine is ≥2 mg/dL, anemia is most likely due to EPO deficiency and measurement of serum EPO levels is usually not indicated. 1
In routine anemia workup: The standard approach focuses on hemoglobin measurement, iron studies (serum iron, TIBC, ferritin, transferrin saturation), reticulocyte count, and evaluation for other reversible causes rather than EPO measurement. 1
When EPO Testing IS Useful
The primary clinical indication for serum EPO measurement is differentiating polycythemia vera from secondary polycythemia in patients with absolute erythrocytosis. 1, 2
Diagnostic Thresholds in Polycythemia
EPO <2.9 mU/mL: Highly suggestive of polycythemia vera, with 87% of PV patients having levels below the normal range (3.3 IU/L), providing 97% specificity and 97.8% positive predictive value. 1, 2
EPO <1.4 IU/L: Allows specific diagnosis of 65.6% of untreated polycythemia vera cases. 2
EPO >13.7-15.1 IU/L: Suggests secondary polycythemia, with all secondary polycythemia patients showing elevated levels (mean 121.7 ± 242 U/L). 1, 2, 3
Normal EPO levels (7.0 ± 2.5 U/L): Consistent with relative polycythemia. 3
Technical Considerations for EPO Measurement
Assay Methods
Enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) are the preferred methods, showing high correlation (r = 0.95) and similar sensitivity. 2, 4
ELISA advantages: Less time-consuming, more convenient, and avoids radioisotope use compared to RIA. 4
Bioassays (EPOS): Not suitable for clinical assessment as they measure bone marrow proliferative activity in response to multiple growth regulators, not just EPO, resulting in falsely elevated values. 4
Sample Requirements
EDTA plasma is recommended for most high-sensitivity methods with proven diagnostic capability for polycythemia vera. 5
Serum samples are acceptable for some methods, though sample stability varies significantly between different assay methods. 5
Normal Reference Ranges
Adults: 18-22.5 mU/mL (mean values vary slightly by assay method). 4, 6
No significant sex difference in normal subjects, though some studies show slightly higher levels in females (20.5 ± 13 mU/mL) versus males (16.5 ± 10 mU/mL). 4
Age consideration: Older subjects may have slightly higher EPO levels than younger subjects. 6
Clinical Pitfalls
Most EPO assay methods lack adequate sensitivity for measuring low EPO concentrations and have poor diagnostic sensitivity for polycythemia vera or EPO deficiency states. 5
In non-renal anemia: Serum EPO levels are usually elevated as a compensatory mechanism, making low levels particularly significant. 1
In anemia of chronic disease: Inflammatory cytokines suppress endogenous EPO production, but EPO measurement is not routinely needed for diagnosis. 1
EPO resistance: Endogenous EPO levels >500 IU/L indicate EPO resistance, and exogenous EPO therapy is unlikely to be effective. 1
Predictive value for EPO therapy response: Baseline endogenous EPO <100 mU/mL predicts better response to exogenous EPO treatment in various diseases. 1