We do not control or have responsibility for the content of any third-party site. Testing for the JAK2 V617F mutation and an erythropoietin (EPO) level helps differentiate secondary polycythemia from polycythemia vera. 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. 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. In secondary polycythemia, the number of red blood cells (RBCs) is increased as a result of an underlying condition. Ann Intensive Care. Musculoskeletal and Connective Tissue Disorders. 1999;74:159-162, 2. 8):viii37-viii41, 4. Abnormal EPO levels also may be seen in renal failure. Drug levels can only be roughly estimated from the cross reactivity of the compounds in EPO assays. Please confirm that you are a health care professional. Such increases result in inappropriate secondary polycythemias. Intervals are Mayo-derived, unless otherwise designated. In individuals with polycythemia vera, EPO levels are abnormally low. In secondary erythrocytosis, only red blood cells (RBCs) are increased, whereas in polycythemia vera, RBCs, white blood cells (WBCs), and platelets will usually be increased. 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. High blood levels of RBC, hemoglobin, hematocrit, or oxygen suppress the release of EPO. A low erythropoietin (EPO) level is a minor diagnostic criterion for polycythemia vera (PV). Medications 6. Standard hemoglobin electrophoresis may be normal and cannot reliably exclude this cause of erythrocytosis. This has been linked to increased plasma viscosity. Low erythropoietin (EPO) level may have only moderate predictive accuracy for polycythemia vera (PV), according to study results published in Blood Cells, Molecules and Diseases. 2011 March;1(3). The Manual was first published as the Merck Manual in 1899 as a service to the community. For questions regarding the diagnostic investigation of erythrocytosis and the utility of specific laboratory tests such as the erythropoietin level, we searched MEDLINE to January 2020 for terms such as “polycythemia vera,” “erythrocytosis” or “secondary … A 61-year-old obese Caucasian male with past medical history of smoking, hypertension, chronic obstructive pulmonary disease (COPD), and sleep apnea presented to the hematology clinic with polycythemia. 1995;70:673-677, 3. Conversely, an EPO level >3.3 IU/L has a sensitivity of 97% for detecting secondary polycythemia. This phenomenon is most pronounced in patients with EPO levels within approximately 2-times the upper limit of the normal population reference interval. Showed that the erythropoietin level was 15.24 ± 2.6 in stage 1, 22.61 ± 5.68 in stage 2, 33.59 ± 4, in stage 3, then 17.9 ± 3.3 in stage 4. Am J Hematol. In secondary polycythemia, your EPO level will be high and you’ll have a high red blood cell count. Because in some cases the elevated hematocrit is physiologic, phlebotomy should be limited to the extent necessary to relieve symptoms (in contrast to polycythemia vera, where the goal is to normalize the hematocrit). For optimal results in serial patient monitoring, all specimens should be collected at the same time of day. Any elevation of hemoglobin or hematocrit above normal values for age and sex is considered erythrocytosis. In secondary erythrocytosis, only red blood cells (RBCs) are increased, whereas in polycythemia vera, RBCs, white blood cells (WBCs), and platelets will usually be increased. Any elevation of hemoglobin or hematocrit above normal values for age and sex is considered erythrocytosis. A disease or the use of certain drugs can cause this type. Erythropoietin (EPO) levels alone cannot reliably distinguish between primary and secondary polycythemia; EPO levels are within normal limits in some patients with primary polycythemia. Common causes of secondary erythrocytosis include, Less common causes include certain congenital disorders such as, Chuvash polycythemia (in which a mutation in the VHL gene affects the hypoxia-sensing pathway), Right to left arteriovenous shunts in the lungs, Proline hydroxylase 2 and hypoxia-inducible factor 2 alpha (HIF-2α) mutations. Secondary polycythemia is also called secondary erythrocytosis. Moore E, Bellomo R: Erythropoietin (EPO) in acute kidney injury. Abstract 4978. Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. There are no specific assays for measuring recombinant EPO compounds. High blood levels of RBC, hemoglobin, hematocrit, or oxygen suppress the release of EPO. Secondary polycythemia, as occurred in the present case, is caused by an increased serum erythropoietin level. erythropoietin is a hormone that tells your bone marrow to make new blood cells. A low serum-erythropoietin (S-epo) level is a minor criterion of the World Health Organization (WHO) recommendations for diagnosing polycythemia vera (PV) even though previous studies indicate that a normal level does not always rule out PV. Last full review/revision Sep 2020| Content last modified Sep 2020. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically People living at high altitudes may have higher EPO levels than people living at lower altitudes. In tumors secreting erythropoietin, the EPO levels may be abnormally high. Spurious erythrocytosis may occur with hemoconcentration (eg, due to burns, diarrhea, or diuretic use). Injuries 4. Patients with chronic hypoxemia (arterial hemoglobin oxygen concentration < 92%), typically due to lung disease, right-to-left intracardiac shunts, renal transplantation, prolonged exposure to high altitudes, or hypoventilation syndromes, often develop erythrocytosis. In secondary erythrocytosis, only red blood cells (RBCs) are increased, whereas in polycythemia vera, RBCs, white blood cells (WBCs), and platelets will usually be increased. 2006 Oct 18;(4):CD003967, 6. Secondary polycythemia most often develops as a response to chronic hypoxemia, which triggers increased production of erythropoietin by the kidneys. The majority of EPO production is in the kidneys. 1 People living at high altitudes may have higher EPO levels than people living at lower altitudes. A… A patient can present with elevate hemoglobin levels due to secondary polycythemia (SP) as a consequence of hypoxia (smoking, lung or cardiac disease, sleep apnea), as a side effect of certain drugs (diuretics, testosterone or anabolic steroids, erythropoietin), due to some renal disorders, or by exogenous administration of erythropoietin 6 The increased production may be an appropriate (compensatory) physiologic response to hypoxemia, which may result from: chronic obstructive pulmonary disease In primary polycythemia, your red blood cell … This is an overproduction of red blood cells that occurs in response to an event such as low blood oxygen level. The term ‘erythrocytosis’ is derived from Greek words meaning ‘too many red cells’ and should be distinguished from ‘polycythemia’, meaning ‘too many cells in the blood’. In polycythemia vera, the EPO levels are low as a response to an increased production of red blood cells. Normally, EPO levels vary inversely with hematocrit. Secondary polycythemias may either be due to an appropriate or an inappropriate increase in red cell mass. A low erythropoietin (EPO) level is a minor diagnostic criterion for polycythemia vera (PV). An elevated erythropoietin (EPO) level, usually as a secondary response to chronic hypoxemia, leads to secondary polycythemia. addition of EPO.12,13 This unique finding, along with serum EPO levels, forms the basis for a new diagnostic approach, 5 but has the disadvantages of … Primary polycythemia (polycythemia vera) is a neoplastic (clonal) blood disorder characterized by autonomous production of hematopoietic cells. Medicine. Increased RBCs result in compensatory suppression of EPO levels. The link you have selected will take you to a third-party website. © 1995–2021 Mayo Foundation for Medical Education and Research. Clinical Signs With relative polycythemia, vomiting or diarrhea may be pres- A low or normal serum erythropoietin level is diagnostically nonspecific. Describes reference intervals and additional information for interpretation of test results. 1 Erythrocytosis has been defined as a greater than two standard deviation-increase from the age-, sex- and race-adjusted norm in hematocrit or hemoglobin level. Fisher JW: Erythropoietin: physiology and pharmacology update. If an interpretive report is provided, the reference value field will state this. Treatments 5. Increased erythropoietin level may be due to secondary polycythemia. doi: 10.1186/2110-5820-1-3, 8. There is some diurnal variation in EPO levels. Results markedly at variance with presentation should be questioned. EPO production is increased in an attempt to increase the delivery of oxygen by increasing the number of oxygen-carrying RBCs. The Manual was first published as the Merck Manual in 1899 as a service to the community. There are no specific assays for measuring recombinant EPO compounds. 2011;39(7):425-428. doi: 10.1016/j.mpmed.2011.04.009. The trusted provider of medical information since 1899, Reactive Thrombocytosis (Secondary Thrombocythemia). Introduction. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically Macdougall I: Anaemia and chronic renal failure. Primary polycythemia (polycythemia vera) is a neoplastic (clonal) blood disorder characterized by autonomous production of hematopoietic cells. A patient can present with elevate hemoglobin levels due to secondary polycythemia (SP) as a consequence of hypoxia (smoking, lung or cardiac disease, sleep apnea), as a side effect of certain drugs (diuretics, testosterone or anabolic steroids, erythropoietin), due to some renal disorders, or by exogenous administration of erythropoietin 6 Hypoxia stimulates EPO release, which, in turn, stimulates bone marrow erythrocyte production. The most common causes of secondary polycythemia include obstructive sleep apnea, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease (COPD). Physicians may also measure the levels of erythropoietin (EPO), a hormone that causes the bone marrow to produce red blood cells. Tumor-associated erythrocytosis can occur when renal tumors, cysts, hepatomas, cerebellar hemangioblastomas, or uterine leiomyomas secrete erythropoietin. Description Polycythemia means too many red blood cells. Low erythropoietin (EPO) level may have only moderate predictive accuracy for polycythemia vera (PV), according to study results published in Blood Cells, Molecules and Diseases.. Low EPO level can be used to diagnose PV, but there has been debate over its diagnostic value in light of the increasing availability of advanced molecular testing. Recombinant EPO compounds used to treat anemia include epoetin alpha and darbepoetin. This site complies with the HONcode standard for trustworthy health information: verify here. (2)Department of Urology, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Mossuz et al, found that the EPO level in cases of PV ranged between 0.6 to 13.7 IU/L (normal 3.3-13.7) compared with 3.3 to 33.9 IU/L of secondary polycythemia patients.8Only 87% of PV patients had the EPO level below the normal range, and the low EPO level had 97% specificity and 97.8% positive predictive value for diagnosing PV. Polycythemia with Renal Cell Carcinoma and Normal Erythropoietin Level. According to in-house studies, epoetin and darbepoetin show approximately 58% and 36% cross-reactivity, respectively, in the EPO assay. Exp Biol Med. Thus, patients who are anephric have a residual amount of EPO produced by the liver. Author information: (1)Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, USA. Low EPO level can be used to diagnose PV, but there has been debate over its diagnostic value in light of the increasing availability of advanced molecular testing. Evaluation of an individual with suspected PV should start with a detailed medical history and a physical examination by a hematologist-oncologist The medical history should include information about the patient’s: 1. Controversies exist regarding the diagnostic value of a low EPO level when considering increasing availability of advanced molecular testing. Despite the newly-diagnosed polycythemia, the patient denied any significant symptoms or history of blood clots. Secondary erythrocytosis is erythrocytosis that develops secondary to disorders that cause tissue hypoxia, inappropriately increased erythropoietin production, or increased sensitivity to erythropoietin. This diagnosis is suggested by a family history of erythrocytosis; it is established by measuring the P50 (the partial pressure of oxygen at which hemoglobin becomes 50% saturated) and, if possible, determining the complete oxyhemoglobin dissociation curve. Additional specimen workup to eliminate heterophile antibody interference can be performed; call 800-533-1710 for additional information. A total of 80.88% (n = 351) of those diagnosed with PV had a JAK2-V617F mutation compared to only 1.47% (n = 2) whose primary diagnosis was secondary polycythemia. (2)Department of Urology, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Also the total percentage of anemia in COPD patients was 46.3% (19/41), in comparison to 51.3% (21/41) non anemic and 2.4% (1/41) polycythemic. 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. Common causes of secondary erythrocytosis include If no contributing factors can be identified after adequate further study, the possibility that the patient may have developed EPO-antibodies should be considered. , MD, James P. Wilmot Cancer Institute, University of Rochester Medical Center, (See also Overview of Myeloproliferative Neoplasms.). Secondary polycythemia may also be caused by increased levels of erythropoietin, a hormone that stimulates RBC produc-tion. Provides information to assist in interpretation of the test results, Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances, Recommendations for in-depth reading of a clinical nature, Library of PDFs including pertinent information and forms related to the test, Customized Instructions & Shipping Guides, Erythrocytosis Evaluation Testing Algorithm, Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation, Myeloproliferative Neoplasm: A Diagnostic Approach to Peripheral Blood Evaluation. Nephrol Dial Transplant. Common causes of secondary erythrocytosis include Erythropoietin (EPO) blood levels may also be helpful, although the results need to be interpreted carefully, as the level may be high in response to chronic hypoxia. Erythropoietin levels may be increased with certain kidney diseases, and erythropoietin-like substances may be secreted by certain tumors. Lower EPO levels than expected have been seen with anemias associated with the following conditions: rheumatoid arthritis, AIDS, cancer, ulcerative colitis, sickle cell disease, and in premature neonates. 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. The primary treatment is to alleviate the underlying condition, but oxygen therapy may help, and phlebotomy may decrease viscosity and alleviate symptoms. Past illnesses 3. Polycythemia with Renal Cell Carcinoma and Normal Erythropoietin Level. Removal of the lesion is curative. An EPO level <1.4 IU/L is 100% specific for a diagnosis of PV, while an EPO level of >13.7 IU/L is 100% specific for the diagnosis of secondary polycythemia. © 2020 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA), © 2021 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. In addition to the kidneys, the liver also produces a small amount of EPO. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically larger than that of EPO test (0.6765). Erythropoietin (EPO) levels alone cannot reliably distinguish between primary and secondary polycythemia; EPO levels are within normal limits in some patients with primary polycythemia. Cochrane Database Syst Rev. This test is usually done to distinguish polycythemia vera from secondary polycythemia, in which EPO levels are not affected. All Rights Reserved. METHODS: sEpo was assessed in 190 patients with polycythemia of different etiologies. 2003;228:1-14, 5. Appropriate secondary polycythemias (eg, high-altitude living and pulmonary disease) are characterized by hypoxia and a compensatory increase in red cell mass. An elevated erythropoietin (EPO) level, usually as a secondary response to chronic hypoxemia, leads to secondary polycythemia. Therefore, chronic kidney failure may result in decreased EPO production and, subsequently, anemia. Strippoli GFM, Manno C, Schena FP, Craig JC: Haemoglobin and haematocrit targets for the anaemia of chronic kidney disease. It has 3 oligosaccharide chains and a molecular mass of 30.4 kDa. Also the total percentage of anemia in COPD patients was 46.3% (19/41), in comparison to … Evidence used in this review. From developing new therapies that treat and prevent disease to helping people in need, we are committed to improving health and well-being around the world. Serum erythropoietin level is elevated in patients with hypoxia-induced erythrocytosis (or level is inappropriately normal for their elevated hematocrit) and in patients with tumor-associated erythrocytosis. We reviewed current guidelines on the management of polycythemia vera. P50 measures the affinity of hemoglobin for oxygen; a normal result excludes a high oxygen-affinity hemoglobinopathy (a familial abnormality) as the cause of erythrocytosis. 2003;18 (Suppl. In patients who smoke, reversible erythrocytosis results mainly from tissue hypoxia due to elevation of blood carboxyhemoglobin concentration; levels will normalize with smoking cessation. JAK2-V617F mutation compared to only 1.47% (n ¼ 2) whose primary diagnosis was secondary polycythemia. Erythropoietin (EPO) levels alone cannot reliably distinguish between primary and secondary polycythemia; EPO levels are within normal limits in some patients with primary polycythemia. Abstract 4978. Kopel J(1), Sharma P(2), Warriach I(3), Swarup S(4). Erythropoietin levels may be increased with certain kidney diseases, and erythropoietin-like substances may be secreted by certain tumors. 1. Increased RBCs result in compensatory suppression of EPO levels. Darbepoetin alpha is a 165 amino acid glycoprotein that is also produced in mammalian cells. 2 It is clear, however, … After allogeneic bone marrow transplant, impaired EPO response may delay EPO recovery. Results: A large majority of PV patients (87% or 101/116) had a serum Epo level below the normal range in healthy patients (3.3 IU/L), giving this value a specificity of 97% with a 97.8% positive predictive value for the diagnosis of PV. Erythropoietin (EPO) levels alone cannot reliably distinguish between primary and secondary polycythemia; EPO levels are within normal limits in some patients with primary polycythemia. 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. Drug levels can only be roughly estimated from the cross reactivity of the compounds in EPO assays. High oxygen–affinity hemoglobinopathies are very rare. A total of 80.88% (n = 351) of those diagnosed with PV had a JAK2-V617F mutation compared to only 1.47% (n = 2) whose primary diagnosis was secondary polycythemia. People living at high altitudes may have higher EPO levels than people living at lower altitudes. Kopel J(1), Sharma P(2), Warriach I(3), Swarup S(4). When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically larger than that of EPO test (0.6765). Hoagland HC: Myelodysplastic (preleukemia) syndromes: the bone marrow factory failure problem. If JAK2 V617F mutation testing is negative but the EPO level is low, then testing for other mutations in exon 12 and 13 of JAK2 helps identify a small minority of patients with polycythemia vera. Patients with hypergammaglobulinemia associated with multiple myeloma or Waldenstrom disease have impaired production of EPO in relation to hemoglobin concentration. This hormone, which is possibly produced and secreted by the kidneys, stimulates bone marrow production of RBCs. 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. 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). Clinical Signs With relative polycythemia, vomiting or diarrhea may be pres- A low serum-erythropoietin (S-epo) level is a minor criterion of the World Health Organization (WHO) recommendations for diagnosing polycythemia vera (PV) even though previous studies indicate that a normal level does not always rule out PV.