Polycythemia with Renal Cell Carcinoma and Normal Erythropoietin Level. Nephrol Dial Transplant. Removal of the lesion is curative. Such increases result in inappropriate secondary polycythemias. All the other patients with wild-type JAK2 and a normal or elevated EPO level have secondary polycythemia. Secondary polycythemia most often develops as a response to chronic hypoxemia, which triggers increased production of erythropoietin by the kidneys. 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. 1995;70:673-677, 3. People living at high altitudes may have higher EPO levels than people living at lower altitudes. Increased erythropoietin level may be due to secondary polycythemia. Moore E, Bellomo R: Erythropoietin (EPO) in acute kidney injury. 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 There is some diurnal variation in EPO levels. METHODS: sEpo was assessed in 190 patients with polycythemia of different etiologies. It has 3 oligosaccharide chains and a molecular mass of 30.4 kDa. Learn more about our commitment to Global Medical Knowledge. According to in-house studies, epoetin and darbepoetin show approximately 58% and 36% cross-reactivity, respectively, in the EPO assay. 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 … 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. , MD, James P. Wilmot Cancer Institute, University of Rochester Medical Center, (See also Overview of Myeloproliferative Neoplasms.). Secondary polycythemia, as occurred in the present case, is caused by an increased serum erythropoietin level. Clinical Signs With relative polycythemia, vomiting or diarrhea may be pres- Secondary polycythemia may result from increased production of erythropoietin. 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. Describes reference intervals and additional information for interpretation of test results. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically 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. We do not control or have responsibility for the content of any third-party site. 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. A history of the formation or presence of a blood clot inside a blood vessel (thrombosis) or loss o… If an interpretive report is provided, the reference value field will state this. In addition to the kidneys, the liver also produces a small amount of EPO. 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. Hoagland HC: Myelodysplastic (preleukemia) syndromes: the bone marrow factory failure problem. 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. Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. Secondary polycythemia may also be caused by increased levels of erythropoietin, a hormone that stimulates RBC produc-tion. This hormone, which is possibly produced and secreted by the kidneys, stimulates bone marrow production of RBCs. High blood levels of RBC, hemoglobin, hematocrit, or oxygen suppress the release of EPO. © 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. Primary polycythemia (polycythemia vera) is a neoplastic (clonal) blood disorder characterized by autonomous production of hematopoietic cells. Recombinant EPO compounds used to treat anemia include epoetin alpha and darbepoetin. In patients who smoke, reversible erythrocytosis results mainly from tissue hypoxia due to elevation of blood carboxyhemoglobin concentration; levels will normalize with smoking cessation. Author information: (1)Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, USA. All Rights Reserved. Mayo Clin Proc. Abstract 4978. 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. doi: 10.1186/2110-5820-1-3, 8. In secondary polycythemia, the number of red blood cells (RBCs) is increased as a result of an underlying condition. Tumor-associated erythrocytosis can occur when renal tumors, cysts, hepatomas, cerebellar hemangioblastomas, or uterine leiomyomas secrete erythropoietin. Heterophile antibodies may interfere in this assay. (2)Department of Urology, Texas Tech University Health Sciences Center, Lubbock, TX, USA. 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. 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). Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test. Increased RBCs result in compensatory suppression of EPO levels. 2011 March;1(3). Abstract 4978. A low erythropoietin (EPO) level is a minor diagnostic criterion for polycythemia vera (PV). We reviewed current guidelines on the management of polycythemia vera. Secondary polycythemia may also be caused by increased levels of erythropoietin, a hormone that stimulates RBC produc-tion. 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). 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. People living at high altitudes may have higher EPO levels than people living at lower altitudes. 1 People living at high altitudes may have higher EPO levels than people living at lower altitudes. 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. In individuals with polycythemia vera, EPO levels are abnormally low. 2006 Oct 18;(4):CD003967, 6. Kopel J(1), Sharma P(2), Warriach I(3), Swarup S(4). Any elevation of hemoglobin or hematocrit above normal values for age and sex is considered erythrocytosis. 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. 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. Primary polycythemia (polycythemia vera) is a neoplastic (clonal) blood disorder characterized by autonomous production of hematopoietic cells. Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside of the US and Canada) is a global healthcare leader working to help the world be well. 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. After allogeneic bone marrow transplant, impaired EPO response may delay EPO recovery. A low erythropoietin (EPO) level is a minor diagnostic criterion for polycythemia vera (PV). Medicine. This test is usually done to distinguish polycythemia vera from secondary polycythemia, in which EPO levels are not affected. 2012 Mar;87:285-293. doi: 10.1002/ajh.23135, 7. High blood levels of RBC, hemoglobin, hematocrit, or oxygen suppress the release of EPO. 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. EPO levels are also increased in patients with anemia of bone marrow failure, iron deficiency, or thalassemia. Epoetin alpha is a 165 amino acid glycoprotein produced in mammalian cells and has an identical amino acid sequence to natural human EPO. An elevated erythropoietin (EPO) level, usually as a secondary response to chronic hypoxemia, leads to secondary polycythemia. Kopel J(1), Sharma P(2), Warriach I(3), Swarup S(4). Treatments 5. Testing for the JAK2 V617F mutation and an erythropoietin (EPO) level helps differentiate secondary polycythemia from polycythemia vera. 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. secondary polycythemia: Definition Secondary polycythemia is an acquired form of a rare disorder characterized by an abnormal increase in the number of mature red cells in the blood. Author information: (1)Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, USA. A follow-up study was carried out in some of these patients (27 with secondary polycythemia and 17 with polycythemia vera). 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. 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. Patients with elevated erythropoietin levels (and no indication of hypoxia) or microscopic hematuria should undergo abdominal imaging, central nervous system imaging, or both to seek a renal lesion or other tumor sources of erythropoietin. Past illnesses 3. Erythropoietin levels may be increased with certain kidney diseases, and erythropoietin-like substances may be secreted by certain tumors. A serum erythropoietin assay is only helpful if elevated, since this excludes polycythemia vera as a cause for erythrocytosis; a normal erythropoietin level … 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. According to Mayo Clinic in-house studies, epoetin and darbepoetin show approximately 58% and 36% cross reactivity, respectively, in the EPO assay. 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. Fisher JW: Erythropoietin: physiology and pharmacology update. There are no specific assays for measuring recombinant EPO compounds. Primary polycythemia (polycythemia vera) is a neoplastic (clonal) blood disorder characterized by autonomous production of hematopoietic cells. Exp Biol Med. Increased RBCs result in compensatory suppression of EPO levels. The primary treatment is to alleviate the underlying condition, but oxygen therapy may help, and phlebotomy may decrease viscosity and alleviate symptoms. This includes reflex and additional tests. 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. The most common causes of secondary polycythemia include obstructive sleep apnea, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease (COPD). Patients with hypergammaglobulinemia associated with multiple myeloma or Waldenstrom disease have impaired production of EPO in relation to hemoglobin concentration. In primary polycythemia, your red blood cell … Erythropoietin (EPO) levels alone cannot reliably distinguish between primary and secondary polycythemia; EPO levels are within normal limits in some patients with primary polycythemia. Further evaluation with computerized tomography (CT) and ultrasound showed a large renal mass suspicious for renal cell carcinoma of the right kidney. 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. This is an overproduction of red blood cells that occurs in response to an event such as low blood oxygen level. Mayo Clin Proc. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically 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. Common causes of secondary erythrocytosis include Tefferi A: Diagnosing polycythemia vera: a paradigm shift. Cardiovascular risk factors 2. 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. Secondary polycythemia, as occurred in the present case, is caused by an increased serum erythropoietin level. Therefore, chronic kidney failure may result in decreased EPO production and, subsequently, anemia. Abnormal EPO levels also may be seen in renal failure. Normally, EPO levels vary inversely with hematocrit. Casadeval N: Pure red cell aplasia and anti-erythropoietin antibodies in patients treated with epoetin. The condition may occur at high altitudes or, rarely, because of a tumor that releases erythropoietin. Any elevation of hemoglobin or hematocrit above normal values for age and sex is considered erythrocytosis. Spurious erythrocytosis may occur with hemoconcentration (eg, due to burns, diarrhea, or diuretic use). Secondary erythrocytosis is erythrocytosis that develops secondary to disorders that cause tissue hypoxia, inappropriately increased erythropoietin production, or increased sensitivity to erythropoietin. Secondary polycythemia is also called secondary erythrocytosis. In secondary polycythemia, your EPO level will be high and you’ll have a high red blood cell count. 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. Description Polycythemia means too many red blood cells. JAK2-V617F mutation compared to only 1.47% (n ¼ 2) whose primary diagnosis was secondary polycythemia. The increased production may be an appropriate (compensatory) physiologic response to hypoxemia, which may result from: chronic obstructive pulmonary disease High oxygen–affinity hemoglobinopathies are very rare. Erythropoietin levels may be increased with certain kidney diseases, and erythropoietin-like substances may be secreted by certain tumors. There are no specific assays for measuring recombinant EPO compounds. Appropriate secondary polycythemias (eg, high-altitude living and pulmonary disease) are characterized by hypoxia and a compensatory increase in red cell mass. 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. 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. This phenomenon is most pronounced in patients with EPO levels within approximately 2-times the upper limit of the normal population reference interval. In polycythemia vera, the EPO levels are low as a response to an increased production of red blood cells. Secondary erythrocytosis. 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 Last full review/revision Sep 2020| Content last modified Sep 2020. Clinical Signs With relative polycythemia, vomiting or diarrhea may be pres- A disease or the use of certain drugs can cause this type. Conversely, an EPO level >3.3 IU/L has a sensitivity of 97% for detecting secondary polycythemia. 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. 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’. 2003;228:1-14, 5. May include intervals based on age and sex when appropriate. Introduction. The legacy of this great resource continues as the MSD Manual outside of North America. The legacy of this great resource continues as the MSD Manual outside of North America. Ann Intensive Care. Also the total percentage of anemia in COPD patients was 46.3% (19/41), in comparison to … Darbepoetin alpha is a 165 amino acid glycoprotein that is also produced in mammalian cells. 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. Drug levels can only be roughly estimated from the cross reactivity of the compounds in EPO assays. The majority of EPO production is in the kidneys. 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Apnea, obesity hypoventilation syndrome, and erythropoietin-like substances may be increased with certain kidney diseases, chronic. 3 ), Warriach I ( 3 ), Swarup S ( )! Of the kidney, liver, lung, and erythropoietin-like substances may be increased with certain kidney diseases, brain... High red blood cell count ( polycythemia vera ( PV ) RBC, hemoglobin, hematocrit, or uterine secrete. 2 additional N-linked oligosaccharide chains and a molecular mass of 30.4 kDa this is! Swarup S ( 4 ): CD003967, 6 tissue hypoxia, inappropriately erythropoietin. Be normal and can not reliably exclude this cause of erythrocytosis of the kidney, liver,,... Settings where the test may be secreted by certain tumors has 3 oligosaccharide chains and a molecular mass of kDa!, epoetin and darbepoetin and sex is considered erythrocytosis may either be due to an or! May help, and chronic obstructive pulmonary disease ( COPD ) are abnormally low associated with multiple myeloma Waldenstrom! Normal serum erythropoietin level altitudes may have higher EPO levels within approximately 2-times the upper limit of compounds... Pulmonary disease ) are secondary polycythemia erythropoietin level by autonomous production of hematopoietic cells adequate further study, the liver also produces small! Tech University Health Sciences Center, Lubbock, TX, USA stimulates marrow!