Erythropoietin (EPO), Serum
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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, chronic renal failure)
Evaluating patients undergoing EPO replacement therapy who demonstrate an inadequate hematopoietic response
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
The following algorithms are available in Special Instructions:
-Erythrocytosis Evaluation Testing Algorithm
-Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation
-Myeloproliferative Neoplasm: A Diagnostic Approach to Peripheral Blood Evaluation
-Polycythemia Vera Algorithm
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Erythropoietin (EPO), S
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 0.6 mL
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross reject
Mild OK; Gross OK
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Serum||Refrigerated (preferred)||14 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Erythropoietin (EPO), a large (193 amino acid residue) glycoprotein hormone secreted by the kidney, regulates 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 erythrocytes result in compensatory suppression of EPO levels. Findings consistent with polycythemia vera include hemoglobin >18.5 gm/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 renal failure may result in decreased renal EPO production and, subsequently, anemia. In addition to the kidneys, the liver also produces a small amount of EPO. Thus, anephric patients have a residual amount of EPO produced by the liver.
Chronic renal failure patients, 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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
In the appropriate clinical setting (eg, confirmed elevation of hemoglobin >18.5 gm/dL, persistent leukocytosis, persistent thrombocytosis, unusual thrombosis, splenomegaly, and erythromelalgia), polycythemia vera is unlikely when erythropoietin (EPO) levels are elevated and polycythemia vera 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 cause(s) 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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Erythropoietin (EPO) levels alone cannot reliably distinguish between primary and secondary polycythemia; EPO levels are within normal limits in some patients with primary polycythemia.
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 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 Mayo in-house studies, epoetin and darbepoetin show approximately 58% and 36% cross reactivity, respectively, in the EPO assay.
Because results obtained with one commercial EPO assay may differ significantly from those obtained with any other, it is recommended that any serial testing performed on the same patient over time should be performed with the same commercial EPO test.
Heterophilic antibodies may interfere in this assay. Results markedly at variance with presentation should be questioned. Additional specimen workup to eliminate heterophilic antibody interference can be performed; please contact the Mayo Medical Laboratories for additional information.
Lower EPO levels than expected have been seen with anemias associated with the following conditions: rheumatoid arthritis, AIDS, cancer, and ulcerative colitis, sickle cell disease, and in premature neonates.
After allogeneic bone marrow transplant, impaired erythropoietin response may delay erythropoietin recovery.
Patients with hypergammaglobulinemia associated with multiple myeloma or Waldenstrom disease have impaired production of erythropoietin in relation to hemoglobin concentration. This has been linked to increased plasma viscosity.
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. The diurnal variation is minimal in normal individuals (<20%), but in hospitalized patients with a variety of illnesses, as well as ambulatory patients with chronic lung disease, serum EPO concentrations can be 20% to 60% higher at night than early in the morning. This phenomenon is most pronounced in patients with EPO levels within approximately 2-times the upper limit of the normal population reference interval.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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: Minireview: 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. The Cochrane Library, 2005, Volume 2
Method Description Describes how the test is performed and provides a method-specific reference
Testing is performed on the Beckman Coulter DxI 800. The Access erythropoietin (EPO) assay is a 2-site immunoenzymatic "sandwich" assay. A sample is added to a reaction vessel along with the paramagnetic particles coated with mouse monoclonal anti-EPO, blocking reagent and the alkaline phosphatase conjugate. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate Lumi-Phos 530 is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of EPO in the sample. The amount of analyte in the sample is determined from a stored, multi-point calibration curve. (Instruction manual: Beckman Coulter Access EPO, Beckman Coulter Access Immunoassay Systems, Beckman Coulter, Inc, Fullerton CA 2009)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday; 5 a.m.-12 a.m., Saturday; 6 a.m.-6 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test has been cleared or approved 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 Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|EPO||Erythropoietin (EPO), S||15061-5|