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Test ID: EPO Erythropoietin, Serum

Reporting Name

Erythropoietin (EPO), S

Useful For

An aid in distinguishing between primary and secondary polycythemia


Differentiating between appropriate secondary polycythemia (eg, high-altitude living, pulmonary disease, tobacco use) and inappropriate secondary polycythemia (eg, tumors)


Identifying candidates for erythropoietin (EPO) replacement therapy (eg, those with chronic renal failure)


Evaluating patients undergoing EPO replacement therapy who demonstrate an inadequate hematopoietic response

Specimen Type


Specimen Required


Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 0.6 mL

Collection Instructions: Morning collection, 7:30 a.m.-12 p.m. is preferred due to diurnal variation. For more information see Cautions.

Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 14 days
  Frozen  14 days
  Ambient  7 days

Reference Values

2.6-18.5 mIU/mL

Day(s) and Time(s) Performed

Monday through Friday; 6 a.m.-12 a.m.

Saturday; 6 a.m.-5 p.m.

Test Classification

This test has been cleared, approved or is exempt by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
EPO Erythropoietin (EPO), S 15061-5


Result ID Test Result Name Result LOINC Value
EPO Erythropoietin (EPO), S 15061-5

Clinical Information

Erythropoietin (EPO), a large (193 amino acid residue) glycoprotein hormone secreted by the kidney, regulates red blood cell (RBC) production. Normally, EPO levels vary inversely with hematocrit. Hypoxia stimulates EPO release, which, in turn, stimulates bone marrow erythrocyte production. High blood levels of RBC, hemoglobin, hematocrit, or oxygen suppress the release of EPO.


Primary polycythemia (polycythemia vera) is a neoplastic (clonal) blood disorder characterized by autonomous production of hematopoietic cells. Increased RBCs result in compensatory suppression of EPO levels. Findings consistent with polycythemia vera include hemoglobin greater than 18.5 g/dL, persistent leukocytosis, persistent thrombocytosis, unusual thrombosis, splenomegaly, and erythromelalgia (dysesthesia and erythema involving the distal extremities).


Secondary polycythemias may either be due to an appropriate or an inappropriate increase in red cell mass. Appropriate secondary polycythemias (eg, high-altitude living and pulmonary disease) are characterized by hypoxia and a compensatory increase in red cell mass. EPO production is increased in an attempt to increase the delivery of oxygen by increasing the number of oxygen-carrying RBCs. Some tumors secrete EPO or EPO-like proteins; examples include tumors of the kidney, liver, lung, and brain. Such increases result in inappropriate secondary polycythemias.


Abnormal EPO levels also may be seen in renal failure. The majority of EPO production is in the kidneys. Therefore, chronic kidney failure may result in decreased EPO production and, subsequently, anemia. In addition to the kidneys, the liver also produces a small amount of EPO. Thus, patients who are anephric have a residual amount of EPO produced by the liver.


Patients in chronic kidney failure, as well as patients with anemia due to a variety of other causes including chemotherapy, HIV/AIDS, and some hematologic disorders, may be candidates for treatment with recombinant human EPO. Recombinant EPO compounds used to treat anemia include epoetin alpha and darbepoetin. Epoetin alpha is a 165 amino acid glycoprotein produced in mammalian cells and has an identical amino acid sequence to natural human EPO. It has 3 oligosaccharide chains and a molecular mass of 30.4 kDa. Darbepoetin alpha is a 165 amino acid glycoprotein that is also produced in mammalian cells. It has 2 additional N-linked oligosaccharide chains and a molecular mass of 37 kDa. There are no specific assays for measuring recombinant EPO compounds. Drug levels can only be roughly estimated from the cross reactivity of the compounds in EPO assays. According to in-house studies, epoetin and darbepoetin show approximately 58% and 36% cross-reactivity, respectively, in the EPO assay.


In the appropriate clinical setting (eg, confirmed elevation of hemoglobin >18.5 g/dL, persistent leukocytosis, persistent thrombocytosis, unusual thrombosis, splenomegaly, and erythromelalgia), polycythemia vera is unlikely when erythropoietin (EPO) levels are elevated but is likely when EPO levels are suppressed.


EPO levels are also increased in patients with anemia of bone marrow failure, iron deficiency, or thalassemia.


Patients, who have either a poor or no erythropoietic response to EPO therapy, but high-normal or high EPO levels, may have additional, unrecognized causes for their anemia. If no contributing factors can be identified after adequate further study, the possibility that the patient may have developed EPO-antibodies should be considered. This can be a serious clinical situation that can result in red cell aplasia and should prompt expeditious referral to hematologists or immunologists skilled in diagnosing and treating this disorder.

Clinical Reference

1. Tefferi A: Diagnosing polycythemia vera: a paradigm shift. Mayo Clin Proc. 1999;74:159-162

2. Hoagland HC: Myelodysplastic (preleukemia) syndromes: the bone marrow factory failure problem. Mayo Clin Proc. 1995;70:673-677

3. Casadeval N: Pure red cell aplasia and anti-erythropoietin antibodies in patients treated with epoetin. Nephrol Dial Transplant. 2003;18 (Suppl. 8):viii37-viii41

4. Fisher JW: Erythropoietin: physiology and pharmacology update. Exp Biol Med. 2003;228:1-14

5. Strippoli GFM, Manno C, Schena FP, Craig JC: Haemoglobin and haematocrit targets for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003967

6. Tefferi A: Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012 Mar;87:285-293. doi: 10.1002/ajh.23135

7. Moore E, Bellomo R: Erythropoietin (EPO) in acute kidney injury. Ann Intensive Care. 2011 March;1(3). doi: 10.1186/2110-5820-1-3

8. Macdougall I: Anaemia and chronic renal failure. Medicine. 2011;39(7):425-428. doi: 10.1016/j.mpmed.2011.04.009

Analytic Time

1 day

Method Name

Immunoenzymatic Assay


If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-General Request (T239)

-Benign Hematology Test Request (T755)

Mayo Clinic Laboratories | Hematology Catalog Additional Information: