Erythropoietin (EPO)

CPT: 82668
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Test Details

Use

This test is intended as an aid in the diagnosis of anemias and polycythemias. With the advent of the administration of recombinant erythropoietin as a biologic therapy to increase red blood cell mass, an erythropoietin assay may be used also to aid in the prediction and monitoring of response to recombinant erythropoietin treatment of anemia.

Limitations

Erythropoietin (EPO) levels alone cannot reliably distinguish between primary and secondary polycythemia; EPO levels are within normal limits in some patients with primary polycythemia.1

People living at high altitudes may have higher EPO levels than people living at lower altitudes.

This assay cannot distinguish between endogenous and exogenous EPO.

There is some diurnal variation in EPO levels. For optimal results in serial patient monitoring, all specimens should be collected at the same time of day.2

For assays employing antibodies, the possibility exists for interference by heterophile antibodies in the patient sample.1 Patients who have been regularly exposed to animals or have received immunotherapy or diagnostic procedures utilizing immunoglobulins or immunoglobulin fragments may produce antibodies (eg, HAMA, that interfere with immunoassays). Additionally, other heterophile antibodies (such as human antigoat antibodies) may be present in patient samples. Such interfering antibodies may cause erroneous results. Carefully evaluate the results of patients suspected of having these antibodies.

Because results obtained with one commercial EPO assay may differ significantly from those obtained with another, it is recommended that serial testing performed on the same patient over time should be performed with the same commercial EPO test.1

Lower EPO levels than expected have been seen in anemias associated with the following: rheumatoid arthritis, acquired immunodeficiency syndrome, cancer, ulcerative colitis, sickle cell disease, and in premature neonates.1

Methodology

Immunochemiluminometric assay (ICMA)

Reference Interval

2.6−18.5 mIU/mL

Additional Information

Erythropoietin (EPO), a glycoprotein (~30,400 daltons) produced primarily by the kidney, is the principal factor regulating red blood cell production (erythropoiesis) in mammals.3 Renal production is regulated by changes in oxygen availability. Normally, EPO levels vary inversely with hematocrit. Under conditions of hypoxia, the level of EPO in the circulation increases, leading to increased production of red blood cells. Conversely, a high hematocrit should suppress the release of EPO.

The over-expression of EPO may be associated with certain pathophysiological conditions.4 Primary polycythemia (polycythemia vera) is a neoplastic (clonal) blood disorder characterized by EPO-independent, autonomous production of erythrocytic progenitors from abnormal bone marrow stem.5 The majority of polycythemia vera cases are caused by oncogenic mutations that constitutively activate the JAKSTAT signal transduction pathway, such as JAK2V617F, or exon 12 mutations or LNK mutations. In most cases, decreased levels of EPO are found in the serum of affected patients.5 Conversely, various types of secondary polycythemias are associated with the production of elevated levels of EPO.5-8 The overproduction of EPO may be an adaptive response associated with conditions that produce tissue hypoxia, such as living at a high altitude, chronic obstructive pulmonary disease, cyanotic heart disease, sleep apnea, high oxygen affinity hemoglobinopathy, smoking, or localized renal hypoxia. In other instances, elevated EPO levels are the result of production by neoplastic cells. Tumors that have been associated with an inappropriate EPO production include cerebellar hemangioblastomas, uterine leiomyomas, pheochromocytoma, renal cell carcinoma, hepatocellular carcinoma, parathyroid adenomas, and meningiomas.6

Deficient EPO production is found in conjunction with certain forms of anemia.9,10 These include anemia of renal failure, end-stage renal disease,11 hypothyroidism, and malnutrition. EPO levels are often measured in patients with chronic kidney disease to assess the kidneys' continued ability to produce erythropoietin. Anemias of chronic disease (chronic infections, autoimmune diseases, rheumatoid arthritis, AIDS, malignancies), are characterized by a blunted response of erythroid progenitors to EPO. Other forms of anemia can be associated with EPO-independent causes, and affected individuals show elevated levels of EPO. These forms include aplastic anemias, iron deficiency anemias, thalassemia, megaloblastic anemias, pure red cell aplasias, and myelodysplastic syndromes.12

Recombinant human EPO (rhEPO) is administered clinically to stimulate red cell production in patients with chronic kidney disease, HIV-infected patients treated with zidovudine, patients undergoing myelosuppressive chemotherapy treatment, and other anemic patients (as an alternative to blood transfusion.)13,14 Several investigators have reported that in chemotherapy-treated cancer patients, baseline EPO levels of greater than 500 mIU/mL predicts unresponsiveness to EPO therapy. Endogenous serum erythropoietin levels are measured as a qualification criterion for rhEPO treatment of anemia in HIV-infected patients taking zidovudine.13

Pretransfusion erythropoietin levels have also been used to predict patients with myelodysplastic syndromes that are likely to respond to rhEPO treatment.12,15 rhEPO is used by some athletes as a performance enhancing drug in an effort to increase endurance and oxygen capacity by increasing the red blood cell count.16 This inappropriate use of the drug can result in adverse clinical consequences due to hypertension and increased blood viscosity. Its use has been prohibited by most sports organizations.

Specimen Requirements

Specimen

Serum

Volume

0.5 mL

Minimum Volume

0.3 mL (Note: This volume does not allow for repeat testing.)

Container

Red-top tube or gel-barrier tube

Collection

If a red-top tube is used, transfer separated serum to a plastic transport tube.

Storage Instructions

Maintain specimen at room temperature.

Stability Requirements

Temperature

Period

Room temperature

14 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3

Clinical Information

Footnotes

1. Beckman Coulter. Access Erythropoietin. 2009. Package insert.7699542
2. Pasqualetti P, Casale R. No influence of aging on the circadian rhythm of erythropoietin in healthy subjects. Gerontology. 1997; 43(4):206-209.9222748
3. Fisher JW. Erythropoietin: Physiology and pharmacology update. Exp Biol Med (Maywood). 2003 Jan; 228(1):1-14.12524467
4. Koury MJ. Erythropoietin: the story of hypoxia and a finely regulated hematopoietic hormone. Exp Hematol. 2005 Nov; 33(11):1263-1270.16263408
5. Passamonti F. How I treat polycythemia vera. Blood. 2012 Jul 12;120(2):275-284.22611155
6. Patnaik MM, Tefferi A. The complete evaluation of erythrocytosis: Congenital and acquired. Leukemia. 2009 May; 23(5):834-844.19295544
7. Kremyanskaya M, Mascarenhas J, Hoffman R. Why does my patient have erythrocytosis? Hematol Oncol Clin North Am. 2012 Apr; 26(2):267-283:vii-viii.20008248
8. McMullin MF. Idiopathic erythrocytosis: A disappearing entity. Hematology Am Soc Hematol Educ Program. 2009:629-635.7699542
9. Steensma DP, Tefferi A. Anemia in the elderly; how should we define it, when does it matter, and what can be done? Mayo Clin Proc. 2007 Aug; 82(8):958-966.17673065
10. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005 Mar 10; 352(10):1011-1023.15758012
11. Mehdi U, Toto RD. Anemia, diabetes, and chronic kidney disease. Diabetes Care. 2009 Jul; 32(7):1320-1326.19564475
12. Barzi A, Sekeres MA. Myelodysplastic syndromes: A practical approach to diagnosis and treatment. Cleve Clin J Med. 2010 Jan; 77(1):37-44.20048028
13. Aranesp® (darbepoetin alfa) directional insert created July 26, 2012; accessed at http://pi.amgen.com/united_states/aranesp/ckd/aranesp_pi_hcp_english,pdf on July 20, 2013.
14. Procrit® (Epoetin alfa) directional insert created July 26, 2012; accessed at http://www.procrit.com/sites/all/themes/procrit/resources/ProcritBooklet.pdf on July 20, 2013.
15. Santini V. Clinical use of erythropoietic stimulating agents in myelodysplastic syndromes Oncologist. 2011; 16 Suppl 3:35-42.21930833
16. Jelkmann W, Lundby C. Blood doping and its detection. Blood. 2011 Sep 1; 118(9):2395-2404.21652677

References

Erythropoietin Reaches the Pharmacy. Lancet. 1989 Nov 25; 2(8674):1252-1254 (editorial). 2573763
Eschbach JW, Adamson JW. Guidelines for recombinant human erythropoietin therapy. Am J Kidney Dis. 1989 Aug; 14(2 Suppl 1):2-8. 2667349
Groopman JE, Molina JM, Scadden DT. Hematopoietic growth factors. Biology and clinical applications. N Engl J Med. 1989 Nov 23; 321(21):1449-1459. 2682244
Hubbard JD, Wheeler DJ. Erythropoietin measurement by EIA. Lab Med. 1989; 20:849-854.
Johnson GR. Erythropoietin. Br Med Bull. 1989; 45(2):506-514. 2688815
Jones EH. Recombinant human erythropoietin. Am J Hosp Pharm. 1989 Nov; 46(11 Suppl 2):S20-S23. 2690606
Paganini EP, Latham D, Abdulhadi M. Practical considerations of recombinant human erythropoietin therapy. Am J Kidney Dis. 1989 Aug; 14(2 Suppl 1):19-25. 2667348
Spivak JL. Erythropoietin. Blood Rev. 1989 Jun; 3(2):130-135. 2673445
Zanjani ED, Ascensão JL. Erythropoietin. Transfusion. 1989 Jan; 29(1):46-57.2643210

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
140277 Erythropoietin (EPO), Serum 15061-5 081424 Erythropoietin mIU/mL 15061-5

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