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Erythropoietin (EPO)

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CONVENTIONAL UNITS

(Hormone for Red Blood Cell Production – Marker for Anemia Evaluation & Renal Function)

Synonyms

  • Erythropoietin
  • EPO
  • Erythropoiesis-stimulating hormone
  • Hematopoietin
  • Renal erythropoietic factor

Units of Measurement

  • mIU/mL (milli–International Units per mL)
  • IU/L (International Units per liter)

Conversions

1 mIU/mL=1 IU/L1\ \text{mIU/mL} = 1\ \text{IU/L}1 mIU/mL=1 IU/L

(They are numerically equal because 1 mL × 1000 = 1 L)

Description

Erythropoietin (EPO) is a glycoprotein hormone primarily produced by the kidneys (90%) and to a lesser extent by the liver (10%).

Its main function:

  • Stimulate red blood cell (RBC) production in the bone marrow.

EPO release is regulated by:

  • Kidney oxygen tension (hypoxia)
  • HIF-1α (Hypoxia-Inducible Factor)

EPO levels rise in response to:

  • Anemia
  • Hypoxia
  • High altitude
  • Chronic lung disease

Physiological Role

EPO binds to erythroid progenitor cells → promotes:

  • RBC proliferation
  • RBC differentiation
  • Prevention of apoptosis

This increases oxygen-carrying capacity of the blood.

Clinical Significance

Low EPO Levels

Most commonly due to chronic kidney disease (CKD).

Causes of Low EPO:

  1. Chronic Kidney Disease (CKD)
    • Damaged kidneys fail to secrete EPO
    • Leads to normocytic, normochromic anemia
  2. Anemia of Chronic Disease
    • Inflammatory cytokines block EPO response
  3. Bone Marrow Disorders
    • Aplastic anemia
    • Pure red cell aplasia
  4. Hypothyroidism or hypometabolic states

Clinical Features:

  • Fatigue
  • Pallor
  • Low hemoglobin despite normal iron stores

High EPO Levels

Reflects an appropriate or inappropriate response to hypoxia.

Causes of High EPO:

  1. Iron deficiency anemia
  2. Hemolytic anemia
  3. Hypoxia-related conditions
    • COPD
    • Obstructive sleep apnea
    • Congenital heart disease
    • High altitude
  4. EPO-secreting tumors
    • Renal cell carcinoma
    • Hepatocellular carcinoma
    • Uterine fibroids
    • Cerebellar hemangioblastoma
  5. Polycythemia evaluation
    • High EPO → secondary polycythemia
    • Low EPO → polycythemia vera (PV)
  6. Athletic doping
    • Recombinant EPO misuse

Reference Intervals

(Tietz 8E + Mayo + ARUP + WHO standards)
 Reference levels vary widely by lab and assay.

Typical Adult Reference Range

  • 2 – 25 mIU/mL
     (or 2 – 25 IU/L)

Interpretation

EPO LevelSuggestive of
Low EPOCKD anemia, ACD, PV
Normal EPONormal response; mild anemia
High EPOHypoxia, hemolysis, tumors, secondary polycythemia

Key Conversion

1 mIU/mL=1 IU/L1\ \text{mIU/mL} = 1\ \text{IU/L}1 mIU/mL=1 IU/L

Diagnostic Uses

1. Evaluation of Anemia

Helps differentiate:

  • CKD anemia (low EPO)
  • Iron deficiency or hemolysis (high EPO)

2. Polycythemia Workup

  • Low EPO → Polycythemia vera (PV)
  • High EPO → Secondary polycythemia

3. Monitoring ESA Therapy

(Erythropoiesis-stimulating agents: epoetin alfa, darbepoetin)

4. Tumor Marker in Certain Neoplasms

Helpful in detecting:

  • RCC
  • HCC
  • Hemangioblastoma

5. Hypoxia Disorders

To assess chronic hypoxia states (COPD, sleep apnea).

Analytical Notes

  • Serum sample
  • Morning samples preferred
  • Hemolysis minimally affects results
  • EPO measured by immunoassays (CLIA, ELISA)
  • Iron studies must be done alongside EPO

Clinical Pearls

  • CKD patients often have normal marrow but low EPO, making them good candidates for ESA therapy.
  • In polycythemia:
    • Low EPO = Polycythemia Vera (JAK2-positive)
    • High EPO = Secondary polycythemia
  • Athletes using recombinant EPO may have very high levels and abnormal isoform patterns.
  • EPO increases significantly in iron deficiency, unlike anemia of chronic disease.
  • Always interpret EPO with Hb, RBC indices, ferritin, creatinine.

Interesting Fact

EPO became famous worldwide in the 1990s due to sports doping scandals in cycling and athletics - it remains one of the most tested substances in anti-doping programs.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Hematology & Hormones.
  2. KDIGO Guidelines - Anemia in CKD.
  3. WHO Reference Standards for EPO Assays.
  4. Mayo Clinic Laboratories - EPO.
  5. ARUP Consult - Anemia & Polycythemia Workup.
  6. MedlinePlus / NIH - EPO Test.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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