Erythropoietin

Aka: Erythropoietin, Epoetin, Erythropoiesis Simulating Agent

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II. Indications

  1. Illicit use by athletes as ergonomic aid (banned)
  2. Anemia
    1. Chronic Renal Failure
      1. Indicated to maintain Hemoglobin 10-12 mg/dl
      2. Decreases cardiovascular morbidity and mortality
      3. Increases quality of life
    2. Cancer Chemotherapy
      1. Indicated to maintain Hemoglobin >10 g/dl
      2. Contraindicated if serum Erythropoietin >200 mU/ml
      3. Increases Hemoglobin 2 g/dl
      4. Decreases transfusion need
      5. Increases quality of life
      6. Does not improve survival or delay disease progress
        1. Henke (2003) Lancet 362:1255-60 [PubMed]
    3. Anemia secondary to HIV Management (e.g. Zidovudine)
      1. Contraindicated if serum Erythropoietin >500 mU/ml
      2. Increases quality of life (e.g. Energy)
      3. Prolongs AIDS survival
    4. Prophylaxis before elective surgery (non-cardiac)
      1. Indicated before surgery where transfusion is otherwise predicted
    5. Other possible indications (covered by Medicare)
      1. Myelodysplastic Syndrome
      2. Hepatitis C (during treatment)
      3. Inflammatory Bowel Disease
      4. Rheumatoid Arthritis
      5. Systemic Lupus Erythematosus

III. Contraindications

  1. Uncontrolled Hypertension

IV. Mechanism

  1. Erythropoietin
    1. Erythropoietin is an endogenous GlycoproteinHormone, a Cytokine encoded by the human EPO gene
      1. Secreted in response to Hypoxia and Anemia by the Kidney (peritubular capillary endothelium) in adults
      2. In the fetus, Erythropoietin is synthesized in the liver
    2. Increases Erythropoiesis and Red Blood Cell volume
      1. Stimulates the proliferation and differentiation of erythroid stem cells in the Bone Marrow
  2. Epoetin
    1. Recombinant synthetic agent chemically similar to endogenous Erythropoietin
    2. Effects are delayed weeks before the Red Blood Cell Counts rise

V. Precautions

  1. Not a substitute for Blood Products in acute severe, symptomatic Anemia
  2. Avoid Hemoglobin targets above 11 g/dl (higher risk of cardiovascular and thrombotic events)
    1. Use the lowest effective dose
  3. Iron Supplementation if needed
    1. Check for Iron Deficiency before administration

VI. Medications

  1. Darbepoetin
  2. Epoetin Alfa
  3. Methoxy Polyethyelene Glycol Epoetin Beta

VII. Adverse Effects

  1. Hypertension (25% of Renal Failure patients)
    1. Hypertensive Encephalopathy
    2. Seizures
  2. Thrombotic events (e.g. Myocardial Infarction)
  3. May promote growth of certain Breast Cancers

VIII. References

  1. (2001) Med Lett Drugs Ther 43(1104):40-1 [PubMed]
  2. (2001) Am J Kidney Dis 37(suppl 1):S182 [PubMed]
  3. Andrade (1996) Am J Orthop 25:533 [PubMed]
  4. Demetri (1998) J Clin Oncol 16:3412 [PubMed]
  5. Henry (1992) Ann Intern Med 117:739 [PubMed]
  6. Moore (1999) Clin Infect Dis 29:44 [PubMed]
  7. Tsakiris (2000) Nephron 85(suppl 1):2 [PubMed]

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