At a Glance
When To Get Tested?
When you have anemia that your healthcare practitioner suspects may be caused by decreased red blood cell production; when you are producing too many red blood cells
A blood sample drawn from a vein in your arm
Test Preparation Needed?
What is being tested?
Erythropoietin (EPO) is a hormone produced primarily by the kidneys, with small amounts made by the liver. EPO plays a key role in the production of red blood cells (RBCs), which carry oxygen from the lungs to the rest of the body. This test measures the amount of erythropoietin in the blood.
The body uses a dynamic feedback system to help maintain sufficient oxygen levels and a relatively stable number of RBCs in the blood.
- Erythropoietin is produced and released into the blood by the kidneys in response to low blood oxygen levels (hypoxemia). The amount of erythropoietin released depends on how low the oxygen level is and the ability of the kidneys to produce erythropoietin.
- EPO is carried to the bone marrow, where it stimulates production of red blood cells. The hormone is active for a short period of time and then eliminated from the body in the urine.
- As oxygen levels in the blood rise to normal or near normal levels, the kidneys slow production of EPO.
However, if your kidneys are damaged and do not produce enough erythropoietin, then too few RBCs are produced and you can becomes anemic. Similarly, if your bone marrow is unable to respond to the stimulation from EPO, then you may become anemic. This can occur with some bone marrow disorders or with chronic diseases, such as rheumatoid arthritis. (Read Anemia of Chronic Diseases to learn more.)
If you have a condition that affects the amount of oxygen you breathe in, such as a lung disease, you may produce more EPO to try to compensate for the low oxygen level. People who live at high altitudes may also have higher levels of EPO and so do chronic tobacco smokers.
If you produce too much erythropoietin, which can happen with some benign or malignant kidney tumors and with a variety of other cancers, you may produce too many RBCs (polycythemia or erythrocytosis). This can lead to an increase in the blood’s thickness (viscosity) and sometimes to high blood pressure (hypertension), blood clots (thrombosis), heart attack, or stroke. Rarely, polycythemia is caused by a bone marrow disorder called polycythemia vera, not by increased erythropoietin.
How is the test used?
An erythropoietin (EPO) test is used primarily to help diagnose the cause of anemia. An EPO test is usually ordered in follow up to abnormal results on a complete blood count (CBC), such as a low red blood cell (RBC) count and low hemoglobin and hematocrit. These tests help diagnose anemia and give the healthcare practitioner clues as to the likely cause of the anemia. Erythropoietin testing is used to help determine if low EPO may be causing and/or worsening the anemia.
If you have chronic kidney disease, an EPO test may be ordered to evaluate the kidneys’ continued ability to produce enough erythropoietin. Testing can help determine whether you should receive erythropoietin replacement therapy. If the erythropoietin level is low, erythropoietin replacement therapy may help increase red cell production in the bone marrow.
Occasionally, an erythropoietin test may be ordered in follow up to CBC results that show an increased number of RBCs, to help diagnose the cause. Testing may help determine whether the excess production of RBCs (polycythemia or erythrocytosis) is due to an overproduction of erythropoietin or some other cause (e.g., JAK2 mutation, bone marrow disorder).
When is it ordered?
An erythropoietin (EPO) test may be ordered when you have anemia that does not appear to be caused by iron deficiency, vitamin B12 or folate deficiency, decreased lifespan of red blood cells (RBCs; hemolysis), or by excessive bleeding. It may be ordered when the RBC count, hemoglobin, and hematocrit are decreased and the reticulocyte count is inappropriately normal or decreased.
If you have chronic kidney disease, erythropoietin levels may be ordered when your healthcare practitioner suspects that kidney dysfunction could be associated with a decrease in erythropoietin production.
An EPO test may be ordered when a complete blood count shows that you have an increased number of RBCs and a high hematocrit and hemoglobin.
What does the test result mean?
If you have anemia and erythropoietin levels are low or normal, then your kidneys may not be producing enough EPO.
If you have anemia and erythropoietin levels are increased, then the anemia may be due to iron or vitamin deficiency, or a bone marrow disorder.
If you have too many red blood cells (RBCs) and erythropoietin levels are increased, then it is likely that excess erythropoietin is being produced – either by your kidneys or by other tissues in your body. This condition is called secondary polycythemia.
If you have too many RBCs and erythropoietin levels are normal or low, then it is likely that the polycythemia has a cause that is independent of erythropoietin production. This condition is called primary polycythemia.
|Condition present||EPO level||Example(s) of possible cause(s)|
|Anemia (low RBCs, hemoglobin and hematocrit)||Low or normal||Severe kidney disease, anemia of chronic disease|
|Anemia||High||Bone marrow disorder (e.g., myelodysplastic syndrome)|
|Polycythemia (high RBCs, hemoglobin and hematocrit)||High||EPO-producing kidney tumor or other tissue (secondary polycythemia)|
|Polycythemia||Normal or low||Polycythemia vera (primary polycythemia)|
Is there a treatment for low EPO?
A synthetic form of erythropoietin (recombinant human erythropoietin or rh-EPO) may be used as a treatment to help increase RBC production in people with chronic kidney disease and other anemias related to bone marrow suppression and/or failure, such as that due to radiation or chemotherapy treatment for cancer. The drug treatment, which is given through a vein (intravenously) or under the skin (subcutaneous injection), is expensive and its stimulation of the bone marrow lasts only a few hours. The synthetic hormone’s use has been promising, helping to decrease the need for blood transfusions and improving the quality life for many affected people.
In June 2011, The U.S. Food and Drug Administration (FDA) recommended that healthcare professionals adjust the ESAs for more conservative dosing in patients with chronic kidney disease (CKD) to improve the safety of these drugs. The data indicated increased risks of cardiovascular events (e.g., heart attacks and strokes) with ESAs in this patient population.
Can adequate erythropoietin production by my kidneys be restored?
Not directly. If your low EPO is due to a temporary kidney condition, then it may resolve as the kidney condition resolves. In many cases, however, low EPO is due to chronic kidney disease and will not get better over time. Your healthcare practitioner will work with you to address and minimize the effects of the resulting anemia and may treat you with synthetic erythropoietin (i.e., erythropoietin replacement therapy).
Why isn't erythropoietin measured to monitor erythropoietin drug therapy?
It is not used because it is the effect on the bone marrow – reflected by increased RBC and reticulocyte production and increasing hemoglobin – that is important in the resolution of anemia, not the concentration of erythropoietin in the blood. The amount needed will vary from person to person depending on their condition and the responsiveness of their bone marrow.
I’ve heard some athletes are tested for EPO. Why?
Synthetic erythropoietin is also being used by some athletes as a form of “blood doping.” Those who use it are trying to increase their endurance and oxygen capacity by increasing the number of RBCs in their blood. This use of the drug can be dangerous, resulting in hypertension and increasing the viscosity of the blood. Its use has been prohibited by most sports organizations, including the International Association of Athletics Federations, and erythropoietin is now being tested for as part of the Olympics anti-doping program. Read Drug Abuse Testing to learn more.
Is there anything else I should know?
If anemia is due to a vitamin B12, folate, or iron deficiency, then the anemia may persist even when enough erythropoietin is produced. The red blood cells (RBCs) produced in these deficiencies may not be normal in size, shape, and/or hemoglobin content.
Pregnant women, chronic smokers, and people with lung disease, or who live at high altitudes may have increased levels of erythropoietin.
Sources Used in Current Review
2020 review performed by Hoda Hagrass MD, Ph.D., Assistant Professor of Pathology and Medical Director of Clinical Chemistry and Immunology, UAMS, and ACH.
FDA Drug Safety Communication: Modified dosing recommendations to improve the safe use Erythropoiesis-Stimulating Agents (ESAs) in chronic kidney disease. Available online at https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-modified-dosing-recommendations-improve-safe-use-erythropoiesis. Accessed on 10/4/2020.
Erythropoietin test. MedlinePlus Medical Encyclopedia. Available online at https://medlineplus.gov/ency/article/003683.htm. Accessed on 10/4/2020.
Kalantar-Zadeh K. History of Erythropoiesis-Stimulating Agents, the Development of Biosimilars, and the Future of Anemia Treatment in Nephrology. Am J Nephrol. 2017;45(3):235-247. doi: 10.1159/000455387. Epub 2017 Feb 1. PMID: 28142147; PMCID: PMC5405152.
World Anti-doping Agency. UFC Prohibited List (August 31, 2019). Available online at https://ufc.usada.org/wp-content/uploads/UFC-Prohibited-List.pdf. Accessed on 10/5/2020.
Kaushansky K. Hematopoiesis and hematopoietic growth factors. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 26th ed. Philadelphia, PA: Elsevier; 2020:chap 147.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.
Walling, A. (2004 April 1). Erythropoietin Improves Anemia but Not Cancer Control. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20040401/tips/13.html.
(©2005). Erythropoietin. ARUP’s Guide to Clinical Laboratory Testing [On-line information]. Available online at http://www.aruplab.com/guides/clt/tests/clt_a241.jsp#1147927.
Hart, J. (2004 January 16). Erythropoietin. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003683.htm.
Eckardt, K. (2001). After 15 years of success—perspectives of erythropoietin therapy. Nephrol Dial Transplant (2001) 16: 1745-1749 [On-line journal]. Available online at http://ndt.oxfordjournals.org/cgi/content/full/16/9/1745.
Bahlmann, F. et. al. (2004). Erythropoietin: is it more than correcting anaemia? Nephrol Dial Transplant (2004) 19: 20-22 [On-line journal]. Available online at http://ndt.oxfordjournals.org/cgi/content/full/19/1/20.
Denker, B. (2004 March). Erythropoietin: From Bench to Bedside. Nephrology Rounds 2(3) [On-line journal]. Available online at http://www.cardiologyrounds.org/crus/nephUS_0304.pdf#search=’erythropoietin’.
Youngerman-Cole, S. (2004 November 17). Erythropoietin. Kaiser Permanente [On-line information]. Available online through http://prospectivemembers.kaiserpermanente.org.
Abramson, S. and Abramson, N. (1999 February 15). ‘Common’ Uncommon Anemias. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/990215ap/851.html.
(2005 March). IAAF EPO Testing Protocol. International Association of Athletics Federations [On-line information]. Available online at http://www.iaaf.biz/newsfiles/28888.pdf#search=’erythropoietin,%20testing’.
Snively, C. and Gutierrez, C. (2004 November 15). Chronic Kidney Disease: Prevention and Treatment of Common Complications. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20041115/1921.html.
Goodnough, L.T. (2004). Blood Doping: From Iron to Gold? American Society of Hematology, ASH Online [On-line information]. Available online at http://www.hematology.org/meeting/2004/newsdaily/issue_3/Blood_Doping.cfm.
U.S. Food and Drug Administration News. FDA Strengthens Safety Information on Erythropoietin-Stimulating Agents (ESAs). (Online information, accessed March 2007). Available online at http://www.fda.gov/bbs/topics/NEWS/2007/NEW01582.html.
Healthday, MedlinePlus. FDA Tightens Warnings on Anemia Drugs. March 9, 2007. (Online information, accessed April 2007). Available online at http://www.nlm.nih.gov/medlineplus/news/fullstory_46388.html.
Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby’s Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 406-407.
Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 364-365.
Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition]. Pp 672.
Grund, S. (2007 August 27, Updated). Erythropoietin test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003683.htm. Accessed on 11/22/08.
Artunc, F. and Risler, T. (2007 November 6). Serum Erythropoietin Concentrations and Responses to Anaemia in Patients With or Without Chronic Kidney Disease. Medscape from Nephrol Dial Transplant. 2007;22(10): 2900-2908 [On-line information]. Available online at http://www.medscape.com/viewarticle/564922. Accessed on 11/22/08.
(2008 October). Anemia in Kidney Disease and Dialysis. National Kidney and Urologic Diseases Information Clearinghouse [On-line information]. Available online at http://kidney.niddk.nih.gov/kudiseases/pubs/anemia/. Accessed on 11/22/08.
(2007 August). Your Kidneys and How They Work. National Kidney and Urologic Diseases Information Clearinghouse [On-line information]. Available online at http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/. Accessed on 11/22/08.
Dugdale, D. (Updated 2011 August 14). Erythropoietin test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003683.htm. Accessed April 2012.
(© 1995-2012). Test ID: EPO Erythropoietin (EPO), Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/80173. Accessed April 2012.
Moore, E. and Bellomo, R. (2011 March 21). Erythropoietin (EPO) in acute kidney injury. Annals of Intensive Care 2011, 1:3 [On-line information]. Available online at http://www.annalsofintensivecare.com/content/1/1/3. Accessed April 2012.
(Updated 2011 November 14) Kidney Failure: What to Expect. National Kidney and Urologic Diseases Information Clearinghouse [On-line information]. Available online at http://kidney.niddk.nih.gov/kudiseases/pubs/expect/. Accessed April 2012.
(Updated 2010 September 9). Anemia in Kidney Disease and Dialysis. National Kidney and Urologic Diseases Information Clearinghouse [On-line information]. Available online at http://kidney.niddk.nih.gov/kudiseases/pubs/anemia/. Accessed April 2012.
Lerma, E. and Stein, R. (Updated 2012 March 28). Anemia of Chronic Disease and Renal Failure. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1389854-overview. Accessed April 2012.
Pagana, K. D. & Pagana, T. J. (© 2011). Mosby’s Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 414-415.
(2010) Amer, J. et. al. Anemia. The Antioxidant Effect of Erythropoietin on Thalassemic Blood Cells. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065733/. Accessed Sept 2016.
(Mar 2011) Jelkmann, W. The Journal of Physiology. Regulation of Erythropoietin Production. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082088/. Accessed Sept 2016.
(2011). Locatelli, F. and Del Vecchio L. Oncologist. Erythropoiesis-stimulating agents in renal medicine. Available online at http://www.ncbi.nlm.nih.gov/pubmed/21930831. Accessed Sept 2016.
(Sept 2015). MedlinePlus. Erythropoietin Test. Available online at https://www.nlm.nih.gov/medlineplus/ency/article/003683.htm. Accessed Sept 2016.
(Sept 2014) Medscape. Reticulocyte Count and Hemoglobin Content. Available online at http://emedicine.medscape.com/article/2086146-overview#a2. Accessed Sept 2016.
(Aug 2004) Noakes, TD. New England Journal of Medicine. Tainted Glory – Doping and Athletic Performance. Available online at http://www.nejm.org/doi/full/10.1056/NEJMp048208. Accessed Sept 2016.