Materiały źródłowe

• #1 Diagnosis and management of congenital and idiopathic erythrocytosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3627324/

  An erythrocytosis occurs when there is an increased red-cell mass. The diagnostic pathway starts with a careful history and examination followed by measurement of the erythropoietin (EPO) levels. This allows a division of those patients with a low EPO level, who can then be investigated for primary causes of erythrocytosis, and those with a normal or high EPO level, where the oxygen-sensing pathway needs to be explored further. […] The initial issue, once the presence of an erythrocytosis has been established, is to determine the cause. An erythrocytosis can be primary where there is an intrinsic defect in the bone marrow resulting in increased red-cell production. In contrast, a secondary erythrocytosis arises when something else drives the production of red cells. […] The second category is those with an inappropriately normal or raised EPO level, which suggests a secondary cause for the erythrocytosis, and further investigations should be directed toward a search for secondary causes, including defects in the oxygen-sensing pathway.

• #2

  https://link.springer.com/article/10.1007/s00277-021-04546-4

  Erythrocytosis has a diverse background. While polycythaemia vera has well defined criteria, the diagnostic approach and management of other types of erythrocytosis are more challenging. The aim of study was to retrospectively analyse the aetiology and management of non-clonal erythrocytosis patients referred to a haematology outpatient clinic in an 8-year period using a 3-step algorithm. The first step was inclusion of patients with Hb185 g/L and/or Hct0.52 in men and Hb165 g/L and/or Hct0.48 in women on two visitstwo months apart, thus confirming true erythrocytosis. […] The study demonstrates real-life management of non-clonal erythrocytosis which could be optimized using a 3-step diagnostic algorithm. […] The causal diversity of erythrocytosis is wide and therefore requires complex diagnostic algorithms. It can have a primary or secondary cause, and both can have either congenital or acquired origin.

• #3 Erythrocytosis: Diagnosis and investigation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/38695361/

  An absolute erythrocytosis is present when the red cell mass is greater than 125% of the predicted. This is suspected when the hemoglobin or hematocrit is above the normal range. An erythrocytosis can be classified as primary or secondary and congenital or acquired. The commonest primary acquired disorder is polycythemia vera. The diagnostic criteria for PV have evolved over time and this is the main diagnosis managed in hematology clinics. […] In order to explore for a cause of erythrocytosis, measurement of the erythropoietin level is a first step. A low erythropoietin level indicates a primary cause and a normal or elevated level indicates a secondary etiology. Further investigation is then dictated by initial findings and includes mutational testing with PCR and NGS for those in whom a congenital cause is suspected. Following this possibly bone marrow biopsy, scans, and further investigation as indicated by history and initial findings. Investigation is directed toward the identification of those with a hematological disorder which would be best managed following guidelines in hematology clinics and referral elsewhere in those for whom there are non-hematological reasons for the elevated hemoglobin.

• #4 Erythrocytosis – Primary Care Notebook

  https://primarycarenotebook.com/pages/haematology/erythrocytosis

  Traditionally, polycythaemia describes a group of varied disorders with an increase in the number of circulating red cells above established normal limits (erythrocytosis is the appropriate term since only the red cell lineage is involved in the disease) (1). […] As a guideline, erythrocytosis should be suspected when there is persistently raised venous haematocrit (Hct) (0.52 males, 0.48 females for 2 months) or haemoglobin (in men greater than 18.0 g per L or in women with values greater than 17.0 g per L) (1). […] True increased red cell mass (rather than apparent erythrocytosis) can be assumed when the haematocrit is over 60% in males and 56% in females (2).

• #5 Diagnosis and Treatment of Erythrocytosis – touchONCOLOGY

  https://touchoncology.com/haematology/journal-articles/diagnosis-and-treatment-of-erythrocytosis/

  An erythrocytosis arises when the red cell mass is increased. This can be due to a primary intrinsic defect in the erythroid progenitor cells or secondary to erythropoietin production from some source. […] Investigation should commence with careful clinical evaluation. Determination of the erythropoietin level is then a first step to guide the further direction of investigation. […] Once an erythrocytosis has been established by repeat testing and red cell mass measurement if necessary, it is essential to take a thorough history and make a full physical examination. […] In those where the cause of the erythrocytosis is not clear, a first step in further investigation would be to measure the EPO level. This divides individuals into two groups: those with low or absent levels, who may have a defect in the EPO signalling pathway, and those with inappropriately normal or elevated levels, in whom a source of the EPO must be sought.

• #6 How is Polycythemia Vera Diagnosed? | Hematology-Oncology Associates of CNY

  https://www.hoacny.com/patient-resources/blood-disorders/what-polycythemia-vera/how-polycythemia-vera-diagnosed

  Polycythemia vera (PV) may not cause signs or symptoms for years. The disease often is found during routine blood tests done for other reasons. If the results of your blood tests aren’t normal, your doctor may want to do more tests. […] Your doctor will diagnose PV based on your signs and symptoms, your age and overall health, your medical history, a physical exam, and test results. […] During the physical exam, your doctor will look for signs of PV. He or she will check for an enlarged spleen, red skin on your face, and bleeding from your gums. […] If your doctor confirms that you have polycythemia, the next step is to find out whether you have primary polycythemia (polycythemia vera) or secondary polycythemia. […] Your medical history and physical exam may confirm which type of polycythemia you have. If not, you may have tests that check the level of the hormone erythropoietin (EPO) in your blood.

• #7 Erythrocytosis (Polycythaemia): Definition, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/23468-erythrocytosis

  Erythrocytosis is having a high concentration of red blood cells. Getting diagnosed and receiving treatment can prevent complications associated with erythrocytosis, like life-threatening blood clots. […] Erythrocytosis causes you to have high levels of hematocrit and/or hemoglobin. […] Erythrocytosis is classified based on the blood composition that causes the high concentration of red blood cells. […] Your healthcare provider may perform various tests and procedures to determine what’s causing your high concentration of red blood cells. […] Your provider may perform any of the following tests to diagnose erythrocytosis. […] A complete blood count shows how many red blood cells you have and your hemoglobin and hematocrit levels. […] Your levels of EPO can help your provider determine whether you have primary or secondary erythrocytosis. […] Most causes of erythrocytosis can’t be cured. Instead, treatment can help ease symptoms. […] Your experience depends on what’s causing your erythrocytosis.

• #8 Polycythemia Vera Diagnosis & Treatment – The Patient Story

  https://thepatientstory.com/mpn/polycythemia-vera/diagnosis/

  Polycythemia vera is a complex disease to diagnose as it often does not present any symptoms. Many cases of PV are caught during a routine physical or blood work. After that, a multitude of tests are run to verify the diagnosis. […] Several different tests are used to diagnose polycythemia vera. While the disease is typically initially found during a routine blood best, several other factors and tests play a role in diagnosing PV, including: Complete Blood Count, Physical exam, Blood Smear, Erythropoietin level, Bone marrow aspiration or biopsy, Gene testing. […] Doctors rely on multiple tests and a physical exam to diagnose an individual with polycythemia vera. […] High hemoglobin, hematocrit, red blood cells, white blood cells, and/or platelets may be a sign of PV. However, high levels of any of these readings can also signify other conditions or even an infection. Therefore, the CBC is more a sign that there might be something wrong rather than a diagnosis of PV itself.

• #9 Erythrocytosis: Definition, Causes, and Symptoms

  https://www.healthline.com/health/erythrocytosis

  How is this diagnosed? […] Blood tests can be done to measure your RBC count and erythropoietin (EPO) levels. EPO is a hormone your kidneys release. It increases production of RBCs when your body is low in oxygen. […] People with primary erythrocytosis will have a low EPO level. Those with secondary erythrocytosis may have a high EPO level. […] You can also get tested for the gene mutations that cause erythrocytosis.

• #10 How is Polycythemia Vera Diagnosed? | Hematology-Oncology Associates of CNY

  https://www.hoacny.com/patient-resources/blood-disorders/what-polycythemia-vera/how-polycythemia-vera-diagnosed

  People who have PV have very low levels of EPO. People who have secondary polycythemia usually have normal or high levels of EPO. […] You may have blood tests to diagnose PV. These tests include a complete blood count (CBC) and other tests, if necessary. […] Often, the first test used to diagnose PV is a CBC. The CBC measures many parts of your blood. […] This test checks your hemoglobin (HEE-muh-glow-bin) and hematocrit (hee-MAT-oh-crit) levels. Hemoglobin is an iron-rich protein that helps red blood cells carry oxygen from the lungs to the rest of the body. Hematocrit is a measure of how much space red blood cells take up in your blood. A high level of hemoglobin or hematocrit may be a sign of PV. […] The CBC also checks the number of red blood cells, white blood cells, and platelets in your blood. Abnormal results may be a sign of PV, a blood disorder, an infection, or another condition.

• #11 Erythrocytosis: Diagnosis and investigation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/38695361/

  An absolute erythrocytosis is present when the red cell mass is greater than 125% of the predicted. This is suspected when the hemoglobin or hematocrit is above the normal range. An erythrocytosis can be classified as primary or secondary and congenital or acquired. The commonest primary acquired disorder is polycythemia vera. The diagnostic criteria for PV have evolved over time and this is the main diagnosis managed in hematology clinics. […] In order to explore for a cause of erythrocytosis, measurement of the erythropoietin level is a first step. A low erythropoietin level indicates a primary cause and a normal or elevated level indicates a secondary etiology. Further investigation is then dictated by initial findings and includes mutational testing with PCR and NGS for those in whom a congenital cause is suspected. Following this possibly bone marrow biopsy, scans, and further investigation as indicated by history and initial findings. Investigation is directed toward the identification of those with a hematological disorder which would be best managed following guidelines in hematology clinics and referral elsewhere in those for whom there are non-hematological reasons for the elevated hemoglobin.

• #12 Diagnosis and management of congenital and idiopathic erythrocytosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3627324/

  An erythrocytosis occurs when there is an increased red-cell mass. The diagnostic pathway starts with a careful history and examination followed by measurement of the erythropoietin (EPO) levels. This allows a division of those patients with a low EPO level, who can then be investigated for primary causes of erythrocytosis, and those with a normal or high EPO level, where the oxygen-sensing pathway needs to be explored further. […] The initial issue, once the presence of an erythrocytosis has been established, is to determine the cause. An erythrocytosis can be primary where there is an intrinsic defect in the bone marrow resulting in increased red-cell production. In contrast, a secondary erythrocytosis arises when something else drives the production of red cells. […] The second category is those with an inappropriately normal or raised EPO level, which suggests a secondary cause for the erythrocytosis, and further investigations should be directed toward a search for secondary causes, including defects in the oxygen-sensing pathway.

• #13 Secondary Erythrocytosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/secondary-erythrocytosis

  Erythrocytosis is increased production of red blood cells (erythrocytes). […] Secondary erythrocytosis develops generally as a result of a disorder that increases erythropoietin secretion. Erythropoietin is a hormone made in the kidneys that stimulates the bone marrow to produce red blood cells. […] It is important for doctors to look for it because both primary and secondary erythrocytosis result in too many red blood cells. […] A high level of erythropoietin is often enough for doctors to diagnose secondary erythrocytosis. […] If the level is low, other tests for the primary erythrocytosis (polycythemia vera) will be done. […] Congenital erythrocytosis is usually diagnosed when a person develops symptoms at an early age or has family members who also have erythrocytosis. In addition to blood tests, doctors may do genetic testing to determine the specific cause.

• #14 Erythrocytosis

  https://www.nhs.uk/conditions/erythrocytosis/

  Erythrocytosis can be diagnosed by carrying out a blood test to check: […] A high concentration of red blood cells suggests you have erythrocytosis. […] Your GP may refer you to a haematologist (a specialist in blood disorders) for more tests, to confirm the diagnosis and to determine the underlying cause. […] These may include: […] a blood test to look for the changed JAK2 gene […] Erythrocytosis is sometimes only discovered during a routine blood test for another reason.

• #15 Polycythemia Vera: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0601/p680.html

  Polycythemia vera is one of three stem-cellderived myeloid malignancies commonly known as myeloproliferative neoplasms. It is characterized by erythrocytosis, often with associated leukocytosis and thrombocytosis. The World Health Organization’s major diagnostic criteria include an elevated hemoglobin or hematocrit level, abnormal results on bone marrow biopsy, and presence of the Janus kinase 2 genetic mutation, which is present in approximately 98% of cases. The only minor criterion is a subnormal erythropoietin level, which helps differentiate polycythemia vera from common causes of secondary erythrocytosis such as smoking, sleep apnea, and testosterone use. […] Patients who have PV typically present with elevated hemoglobin and hematocrit levels found incidentally or after laboratory evaluation for patients’ reported symptoms, physical examination findings, or thrombotic/bleeding events. The differential diagnosis of PV includes other myeloproliferative neoplasms and secondary erythrocytosis from smoking, sleep apnea, and androgen use and, rarely, erythropoietin-producing tumors.

• #16 Polycythemia Vera: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17742-polycythemia-vera

  Polycythemia vera is a type of chronic leukemia (blood cancer) that causes your bone marrow to produce too many red blood cells. […] Polycythemia vera (PV) is a blood disorder that causes your body to produce too many red blood cells. […] Polycythemia vera is a type of blood cancer known as myeloproliferative neoplasm (MPN). […] The World Health Organization (WHO) requires three separate criteria to diagnose polycythemia vera: […] Red blood cells may be measured as: High hemoglobin count (protein found in red blood cells). […] High hematocrit levels (percentage of red blood cells). […] High blood volume (red cell mass). […] Bone marrow biopsy showing either: Excess of blood cells in the bone marrow, or Excess of mature megakaryocytes (the cells that make blood platelets). […] The third criteria can be met by showing either: Molecular testing showing the presence of the JAK2 gene mutation, or Blood test showing very low levels of erythropoietin (a hormone produced by your kidneys to stimulate red blood cell production).

• #17 Secondary Polycythemia Workup: Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/205039-workup

  Measuring arterial oxygen saturation is important to exclude generalized hypoxemia as a cause of increased RBC mass. Further investigation may require performing the test while the patient is sleeping. Measured arterial oxygen saturations of less than 92% may be associated with the development of a secondary polycythemia. […] Carboxyhemoglobin levels of greater than 8% in individuals who smoke or who may have occupational exposure to carbon monoxide may be associated with the development of polycythemia.

• #18 Secondary Polycythemia Workup: Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/205039-workup

  Measuring arterial oxygen saturation is important to exclude generalized hypoxemia as a cause of increased RBC mass. Further investigation may require performing the test while the patient is sleeping. Measured arterial oxygen saturations of less than 92% may be associated with the development of a secondary polycythemia. […] Carboxyhemoglobin levels of greater than 8% in individuals who smoke or who may have occupational exposure to carbon monoxide may be associated with the development of polycythemia.

• #19 Polycythemia Vera Diagnostic Workup

  https://www.targetedonc.com/view/polycythemia-vera-diagnostic-workup

  Polycythemia vera (PV) should be suspected based on a number of findings that patients may present with. So, first of all, if CBC shows an elevated hemoglobin or hematocrit, then an evaluation or consideration of polycythemia vera should be made. However, there are other symptoms that a patient may present with. Pruritus without a rash would be a sign of polycythemia vera and a number of other myeloproliferative neoplasms. If patients have unexplained fatigue or night sweats, weight loss, unexplained splenomegaly, these are findings that should trigger an evaluation for polycythemia vera. […] The criteria for the diagnosis of polycythemia vera have changed over the years. […] In a patient where PV is suspected, these definitely should be checked. This DNA-based assay can be done on peripheral blood. A bone marrow biopsy is not required because the mutation, if acquired, will be found in the nuclei of the white blood cells, as well as erythroid precursors and megakaryocytes in the bone marrow.

• #20 Polycythemia vera – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/polycythemia-vera/diagnosis-treatment/drc-20355855

  Your healthcare professional takes a medical history and do a physical exam. […] If you have polycythemia vera, blood tests might show: More red blood cells than usual and, sometimes, an increase in platelets or white blood cells. […] A higher portion of red blood cells that make up total blood volume, called hematocrit measurement. […] Higher level of the iron-rich protein in red blood cells that carries oxygen, called hemoglobin. […] A healthcare professional who suspects that you have polycythemia vera might suggest getting a sample of your bone marrow through a bone marrow aspiration or biopsy. […] Study of your bone marrow or blood might show the gene change that’s linked with the disease. […] In a bone marrow aspiration, a healthcare professional uses a thin needle to remove a small amount of liquid bone marrow.

• #21 NHEP – Overview: Hereditary Erythrocytosis Gene Panel, Next-Generation Sequencing, Varies

  https://www.mayocliniclabs.com/test-catalog/Overview/619019

  Evaluating an individual with JAK2-V617F negative erythrocytosis associated with lifelong sustained increased red blood cell (RBC) mass, elevated RBC count, hemoglobin, or hematocrit […] Providing an extensive genetic evaluation for patients with a personal or family history suggestive of hereditary erythrocytosis […] Comprehensive testing for patients in whom previous targeted gene variant analyses were negative for a specific hereditary erythrocytosis […] Establishing a diagnosis of a hereditary erythrocytosis or related disorder, allowing for appropriate management and surveillance of disease features based on the gene involved […] This evaluation is recommended for patients presenting with lifelong elevation in hemoglobin or hematocrit, usually with a positive family history of similar symptoms. Polycythemia vera should be excluded prior to testing as it is much more common than hereditary erythrocytosis and can be present even in young patients. A JAK2 V617F or JAK2 exon 12 variant should not be present. More sensitive, variant-specific testing for JAK2 V617F is highly recommended prior to ordering this test. Additionally, alpha and beta chain high-oxygen affinity hemoglobin variants should be excluded prior to ordering this test panel

• #22 Panel for Congenital Erythrocytosis / Familial Polycythemia (Code 10050) – BloodGenetics

  https://bloodgenetics.com/panel-congenital-erythrocytosis-familial-policitemia-code-10050/

  Familial polycythemia or congenital erythrocytosis is an inherited hematological disorder, characterized by a high absolute mass of red blood cells caused by an uncontrolled production of red blood cells. […] The diagnosis is based on the evidence of finding relatives with isolated erythrocytosis without splenomegaly, low levels of serum EPO, normal affinity of hemoglobin for oxygen, and erythroid progenitors in the bone marrow exhibiting a hypersensitivity to EPO. […] The differential diagnosis includes polycythemia vera which can be excluded based on the absence of mutations in the JAK2 gene (9p24). […] Polycythemia associated with von Hippel-Lindau syndrome or Chuvash polycythemia or type 2 familial erythrocytosis is due to mutations in the VHL gene (3p25). […] Type 3 familial erythrocytosis is an autosomal dominant disorder due to mutations in the EGLN1 gene (1q42). […] Type 4 familial erythrocytosis is an autosomal dominant disorder characterized by increased serum red blood cell mass and elevated serum hemoglobin and erythropoietin (EPO).

• #23

• #24 Erythrocytosis | eClinpath

  https://eclinpath.com/hematology/polycythemia/

  Erythrocytosis is defined as an increase in red blood cell (RBC) mass, usually absolute, and is also associated with an increased hematocrit (HCT) and hemoglobin concentration. […] An increased HCT or RBC count can be relative (proportional changes of RBC numbers in relation to plasma water) or absolute (a true increase in RBC numbers due to erythropoiesis, i.e. erythrocytosis). […] The different causes of an increased HCT or RBC count can be distinguished on the basis of clinical signs and signalment (dehydration, young horse), response to fluid therapy (relative increases should correct with appropriate fluid treatment), total protein concentration (usually only increased with relative increases due to dehydration), detection of hypoxia (arterial blood gas analysis), cardiovascular and pulmonary evaluation, and searching for underlying causes of increased RBC production, which would result in a true increase in RBC mass or erythrocytosis (such as liver and renal disease, including neoplasia).

• #25 Retrospective Study of High Hemoglobin Levels in 56 Young Adults | Desnoyers | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/375/332

  Proper management depends on the underlying cause. Phlebotomies may be proposed to patients presenting with hyperviscosity related symptoms. […] The current diagnostic approach recommended for the investigation of erythrocytosis systematically includes a search for JAK2(V617F) mutation and serum EPO as the first step in every patient. A positive JAK2(V617F) result should orient the diagnosis and management towards a diagnosis of primary acquired erythrocytosis. A normal or high EPO should guide the clinician towards the search for a secondary cause of acquired erythrocytosis, and when no cause is found, the search for a secondary inherited cause. A negative result for JAK2(V617F) mutation and a low EPO level should be further investigated with a bone marrow biopsy and a search for JAK2 (exon12), and when non-contributory, should prompt a search for inherited primary erythrocytosis.

• #26 Polycythemia Vera – Hematology and Oncology – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/hematology-and-oncology/myeloproliferative-disorders/polycythemia-vera

  Polycythemia vera is a chronic myeloproliferative neoplasm characterized by an increase in morphologically normal red cells (its hallmark), but also white cells and platelets. Diagnosis is made by complete blood count, testing for JAK2 or rarely CALR mutations, and clinical criteria. Increased production confined to the RBC line is termed erythrocytosis; isolated erythrocytosis may occur with polycythemia vera but is more commonly due to other causes (see secondary erythrocytosis). Polycythemia vera is often first suspected because of an abnormal CBC (eg, hemoglobin 16.5 g/dL [ 165 g/L] in men or 16.0 g/dL [ 160 g/L] in women). Thus, an elevated red cell count is the most useful measure of erythrocytosis. […] Polycythemia vera should always be considered in patients with a normal hematocrit but microcytic erythrocytosis and evidence of iron deficiency; this combination of findings is a hallmark of polycythemia vera.

• #27 Hematocrit Levels | HCT Blood Test For Blood Cancer | LLS

  https://www.lls.org/myeloproliferative-neoplasms/polycythemia-vera/diagnosis

  In PV, the bone marrow shows above-normal numbers of blood cells and an abnormal number of the platelet-forming cells called megakaryocytes in the bone marrow. […] If PV is suspected, testing for the JAK2 gene mutation should be performed. The JAK2 V617F mutation is found in more than 95 percent of PV patients. […] Diagnosis requires 3 major criteria OR 2 major criteria + 1 minor criterion. […] Very low erythropoietin level.

• #28 Polycythemia Vera Diagnosis & Treatment – The Patient Story

  https://thepatientstory.com/mpn/polycythemia-vera/diagnosis/

  Most patients diagnosed with polycythemia vera have a mutation of the JAK2 gene. Your doctor may test for this mutation by sending a blood or bone marrow sample for genetic testing. […] In 2016, the World Health Organization (WHO) listed three criteria to diagnose polycythemia vera: Blood test showing elevated red blood cell count measured by a high hemoglobin count, hematocrit levels, or high blood volume; Bone marrow biopsy showing an excess of blood cells in the bone marrow or excess of mature megakaryocytes; Molecular testing demonstrating the presence of the JAK2 gene mutation or blood tests showing low levels of erythropoietin. […] To be diagnosed with polycythemia vera, a patient must meet all three criteria. As you may have noticed, the diagnostic tests previously mentioned are all aimed towards testing for the WHO’s criteria.

• #29 Polycythemia Vera Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/205114-workup

  Diagnostic criteria for PV as per the 2022 revised WHO guidelines include three major criteria and a minor criterion. Diagnosis requires the presence of either all three major criteria or the first two major criteria and the minor criterion. […] The most important diagnostic tests are JAK2 mutation analysis and the serum erythropoietin (Epo) level. A positive JAK2 V617F mutation and a low Epo level confirms the diagnosis of PV. […] A low serum Epo level, which is decreased in nearly all patients with PV who have experienced no recent hemorrhage, distinguishes polycythemia from secondary causes of polycythemia in which the serum Epo level is generally within the reference range or is elevated. […] Measuring arterial oxygen saturation (SaO2) and carboxyhemoglobin (COHb) levels is important to rule out hypoxia as a secondary cause for erythrocytosis.

• #30 Polycythemia Vera: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17742-polycythemia-vera

  Polycythemia vera is a type of chronic leukemia (blood cancer) that causes your bone marrow to produce too many red blood cells. […] Polycythemia vera (PV) is a blood disorder that causes your body to produce too many red blood cells. […] Polycythemia vera is a type of blood cancer known as myeloproliferative neoplasm (MPN). […] The World Health Organization (WHO) requires three separate criteria to diagnose polycythemia vera: […] Red blood cells may be measured as: High hemoglobin count (protein found in red blood cells). […] High hematocrit levels (percentage of red blood cells). […] High blood volume (red cell mass). […] Bone marrow biopsy showing either: Excess of blood cells in the bone marrow, or Excess of mature megakaryocytes (the cells that make blood platelets). […] The third criteria can be met by showing either: Molecular testing showing the presence of the JAK2 gene mutation, or Blood test showing very low levels of erythropoietin (a hormone produced by your kidneys to stimulate red blood cell production).

• #31 Secondary Erythrocytosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/secondary-erythrocytosis

  Erythrocytosis is increased production of red blood cells (erythrocytes). […] Secondary erythrocytosis develops generally as a result of a disorder that increases erythropoietin secretion. Erythropoietin is a hormone made in the kidneys that stimulates the bone marrow to produce red blood cells. […] It is important for doctors to look for it because both primary and secondary erythrocytosis result in too many red blood cells. […] A high level of erythropoietin is often enough for doctors to diagnose secondary erythrocytosis. […] If the level is low, other tests for the primary erythrocytosis (polycythemia vera) will be done. […] Congenital erythrocytosis is usually diagnosed when a person develops symptoms at an early age or has family members who also have erythrocytosis. In addition to blood tests, doctors may do genetic testing to determine the specific cause.

• #32 Erythrocytosis (Polycythemia) in Animals – Circulatory System – Merck Veterinary Manual

  https://www.merckvetmanual.com/circulatory-system/erythrocytosis-polycythemia/erythrocytosis-polycythemia-in-animals

  Erythrocytosis is a relative or absolute increase in the number of circulating RBCs, resulting in the PCV, hematocrit, RBC count, and hemoglobin concentration increasing above reference intervals. […] Absolute erythrocytosis, defined as increased RBC numbers because of increased RBC mass, develops from primary or secondary causes. […] Primary erythrocytosis (polycythemia vera) is a myeloproliferative disease resulting from the autonomous clonal expansion of hematopoietic progenitor cells that has been reported in dogs, cats, horses, and ferrets. […] With absolute erythrocytosis, serum EPO determinations could potentially differentiate primary from secondary causes. […] Routine examination of bone marrow is NOT useful to distinguish primary from secondary erythrocytosis because both conditions show erythroid hyperplasia. As a result, primary erythrocytosis usually is diagnosed by eliminating secondary causes.

• #33 Polycythemia Vera Diagnostic Workup

  https://www.targetedonc.com/view/polycythemia-vera-diagnostic-workup

  The other thing that can be very helpful is the erythropoietin (EPO) level. In a patient with autonomous production of red blood cells, renal production of erythropoietin should be suppressed. So, EPO levels below normal can be very helpful. […] If the patient is presenting with erythrocytosis or polycythemia, then the first thing that needs to be ruled out is just a relative polycythemia due to a decrease in plasma volume; in other words, dehydration. If the patient has an absolute erythrocytosis not due to a decrease in plasma volume, then the physician needs to discern whether this red cell elevation is appropriate and physiologically appropriate. […] There could be pathologic causes of erythrocytosis due to erythropoietin production. EPO can be produced by tumors such as renal cell carcinoma, hepatocellular carcinoma, hemangioblastomas. […] If all of those are ruled out, then polycythemia vera is a likely diagnosis.

• #34 Secondary polycythemia: Its Symptoms, Diagnosis, Treatment, and Management

  https://www.webmd.com/a-to-z-guides/what-is-secondary-polycythemia

  Secondary polycythemia, also known as secondary erythrocytosis or secondary erythrocythemia, is a rare condition in which your body produces an excess amount of red blood cells. […] Diagnosing Secondary Polycythemia […] Based on your symptoms, your doctor may recommend a routine medical exam where they would detail your medical history followed by a thorough physical exam. […] Your doctor may measure your oxygen levels in your blood using an arterial blood gas (ABG) test or other blood tests to measure EPO and red blood cell mass levels. […] Your doctor may also order diagnostic tests like an electrocardiogram, or ECG, to measure heart function as well as imaging tests like an X-ray, CT scan, or ultrasound to detect enlargement of the heart, liver, or spleen.

• #35 Panel for Congenital Erythrocytosis / Familial Polycythemia (Code 10050) – BloodGenetics

  https://bloodgenetics.com/panel-congenital-erythrocytosis-familial-policitemia-code-10050/

  Familial polycythemia or congenital erythrocytosis is an inherited hematological disorder, characterized by a high absolute mass of red blood cells caused by an uncontrolled production of red blood cells. […] The diagnosis is based on the evidence of finding relatives with isolated erythrocytosis without splenomegaly, low levels of serum EPO, normal affinity of hemoglobin for oxygen, and erythroid progenitors in the bone marrow exhibiting a hypersensitivity to EPO. […] The differential diagnosis includes polycythemia vera which can be excluded based on the absence of mutations in the JAK2 gene (9p24). […] Polycythemia associated with von Hippel-Lindau syndrome or Chuvash polycythemia or type 2 familial erythrocytosis is due to mutations in the VHL gene (3p25). […] Type 3 familial erythrocytosis is an autosomal dominant disorder due to mutations in the EGLN1 gene (1q42). […] Type 4 familial erythrocytosis is an autosomal dominant disorder characterized by increased serum red blood cell mass and elevated serum hemoglobin and erythropoietin (EPO).

• #36 Diagnosing or Ruling Out Polycythemia Vera in Patients With Erythrocytosis – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/january-2019/diagnosing-or-ruling-out-polycythemia-vera-in-patients-with-erythrocytosis/

  The first step is to determine how long the patient has had the condition. Does the red cell elevation go back to childhood? If so, the condition is likely congenital. […] If I am able to exclude arterial hypoxia, elevated carbon monoxide, and methemoglobinemia, I measure the erythropoietin level. This is generally low in polycythemia vera and even lower in primary familial and congenital polycythemia. […] The test to identify congenital forms of erythrocytosis is measurement of the hemoglobin-oxygen dissociation curve. […] The morbidity and mortality of Chuvash polycythemia result principally from an increased occurrence of thrombosis that is not relieved and is even increased by phlebotomy; however, the cause is not the high hematocrit but too much HIF, which dysregulates genes in the thrombotic pathway.

• #37 HEMP – Overview: Hereditary Erythrocytosis Mutations, Whole Blood

  https://www.mayocliniclabs.com/test-catalog/overview/61337

  Definitive evaluation of an individual with JAK2-negative erythrocytosis associated with lifelong sustained increased red blood cell (RBC) mass, elevated RBC count, hemoglobin, or hematocrit. […] This test is a third-order test and should be ordered when the patient meets the following criteria: diagnosis of erythrocytosis and JAK2 V617F is negative. […] This evaluation is recommended for patients presenting with lifelong erythrocytosis, usually with a positive family history of similar symptoms. Polycythemia vera should be excluded prior to testing as it is much more common than hereditary erythrocytosis and can be present even in young patients. A JAK2 V617F or JAK2 exon 12 variant should not be present. Additionally, testing to exclude the possibility of a high oxygen affinity hemoglobin variant should be performed before ordering this test.

• #38 Familial erythrocytosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/familial-erythrocytosis/

  Familial erythrocytosis is an inherited condition characterized by an increased number of red blood cells (erythrocytes). The primary function of these cells is to carry oxygen from the lungs to tissues and organs throughout the body. Signs and symptoms of familial erythrocytosis can include headaches, dizziness, nosebleeds, and shortness of breath. The excess red blood cells also increase the risk of developing abnormal blood clots that can block the flow of blood through arteries and veins. If these clots restrict blood flow to essential organs and tissues (particularly the heart, lungs, or brain), they can cause life-threatening complications such as a heart attack or stroke. However, many people with familial erythrocytosis experience only mild signs and symptoms or never have any problems related to their extra red blood cells.

• #39 Diagnosis and management of congenital and idiopathic erythrocytosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3627324/

  Once all the causes of primary and secondary erythrocytosis have been considered, there remains a group for which no cause for the erythrocytosis can be identified. This group is in a category termed idiopathic erythrocytosis. […] The management of a congenital or idiopathic erythrocytosis is much more problematic as there is little evidence available for guidance. […] The therapeutic options for a patient with congenital and erythrocytosis are limited and largely of unproven efficacy. Low-dose aspirin in those without a specific contraindication and venesection to an achievable target HCT are the main treatments to be considered.

• #40

  https://link.springer.com/article/10.1007/s10238-023-01283-y

  Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). […] We demonstrated that most of our cohort (40/56: 71.4%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. […] Once all the causes of primary and secondary erythrocytosis have been considered, there remains a group for which no cause can be identified. This condition is known as idiopathic erythrocytosis (IE). The frequency of IE has been estimated to be 1.1 per 1000 subjects, which is higher than that observed in PV. […] Evidence is lacking to define best management, but aspirin and venesection to a target Hct should be considered. Cytoreductive therapy, to date, is not appropriate for the treatment of patients with erythrocytosis in whom there is no evidence of a malignant clone.

• #41

  https://link.springer.com/article/10.1007/s00277-021-04546-4

  The only primary cause of clonal erythrocytosis is polycythaemia vera (PV), almost always associated with a JAK2 mutation. […] If no cause is found, the patient is diagnosed with idiopathic erythrocytosis (IE). […] It is important to be familiar with the contemporary evaluation of erythrocytosis, utilizing algorithms for efficient testing in the majority of patients in everyday clinical practice. […] The aim of our study was to retrospectively analyse non-clonal erythrocytosis patients from our centre medical records in an eight-year period. Furthermore, our goal was to sample out idiopathic patients for further genetic testing using next-generation sequencing (NGS) to determine possible genetic background. […] The three-step diagnostic algorithm, we used to retrospectively check diagnostic procedures performed in our patients, is a simple tool developed recently at our department to guide haematologists to proper erythrocytosis classification.

• #42

  https://link.springer.com/article/10.1007/s00277-021-04546-4

  Erythrocytosis has a diverse background. While polycythaemia vera has well defined criteria, the diagnostic approach and management of other types of erythrocytosis are more challenging. The aim of study was to retrospectively analyse the aetiology and management of non-clonal erythrocytosis patients referred to a haematology outpatient clinic in an 8-year period using a 3-step algorithm. The first step was inclusion of patients with Hb185 g/L and/or Hct0.52 in men and Hb165 g/L and/or Hct0.48 in women on two visitstwo months apart, thus confirming true erythrocytosis. […] The study demonstrates real-life management of non-clonal erythrocytosis which could be optimized using a 3-step diagnostic algorithm. […] The causal diversity of erythrocytosis is wide and therefore requires complex diagnostic algorithms. It can have a primary or secondary cause, and both can have either congenital or acquired origin.

• #43 Secondary Polycythemia Workup: Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/205039-workup

  Testing for the JAK2 V617F mutation and an erythropoietin (EPO) level helps differentiate secondary polycythemia from polycythemia vera. Positive JAK2 V617F mutation status with a low EPO level confirms the diagnosis of polycythemia vera. 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. JAK2 mutation testing also identifies the rare patients with polycythemia vera who have elevated EPO levels. Patients with wild-type JAK2 and a normal or elevated EPO level have secondary polycythemia. […] When repeated hematocrit levels exceed 52% in males and 47% in females, consideration should be given to measurement of red blood cell (RBC) mass and plasma volume. The RBC mass is increased if it exceeds 35 mg/kg in males and 31 mg/kg in females. However, data from the Polycythemia Vera Study Group showed that if the hematocrit value is 60% or higher, the RBC mass is always increased; formal RBC mass and plasma volume studies are unnecessary in those cases.

• #44 Erythrocytosis – Primary Care Notebook

  https://primarycarenotebook.com/pages/haematology/erythrocytosis

  Traditionally, polycythaemia describes a group of varied disorders with an increase in the number of circulating red cells above established normal limits (erythrocytosis is the appropriate term since only the red cell lineage is involved in the disease) (1). […] As a guideline, erythrocytosis should be suspected when there is persistently raised venous haematocrit (Hct) (0.52 males, 0.48 females for 2 months) or haemoglobin (in men greater than 18.0 g per L or in women with values greater than 17.0 g per L) (1). […] True increased red cell mass (rather than apparent erythrocytosis) can be assumed when the haematocrit is over 60% in males and 56% in females (2).

• #45

  https://link.springer.com/article/10.1007/s00277-021-04546-4

  In the second step of the algorithm, clonal erythrocytosis was ruled out and secondary causes were reviewed. […] After a thorough documentation review of all patients secondary erythrocytosis was found in 34/116 (29%) patients, 15/116 (13%) remained idiopathic despite adequate diagnostics, whereas a quite high number of patients, 67/116 (58%) would need further investigations for characterisation of erythrocytosis according to modern diagnostic algorithms. […] The treatment guidelines for non-clonal erythrocytosis are not clear. […] The three-step algorithm is a useful tool for everyday clinical evaluation of erythrocytosis. Secondary causes of erythrocytosis should be systematically checked and IE patients referred for genetic testing. Only patients with known aetiology of erythrocytosis can be properly managed.

• #46 JAK2 unmutated erythrocytosis: current diagnostic approach and therapeutic views | Leukemia

  https://www.nature.com/articles/s41375-021-01290-6

  In clinical practice, hematology referrals for erythrocytosis are triggered by Hgb/Hct level above 16.5g/dl/49% and 16g/dl/48% in Caucasian males and females, respectively, and should be confirmed by at least two separate blood counts evaluated at different time points. This should be followed by distinguishing true from apparent erythrocytosis; the former is a result of either a clonal MPN, as in PV, or a non-clonal process resulting in secondary erythrocytosis. It is also important to recognize inapparent (masked) erythrocytosis in which an increase in red cell mass (RCM) is accompanied by a concomitant increase in plasma volume and therefore masked by a normal Hgb/Hct. […] Once PV has been conclusively ruled out, we entertain the possibility of either hereditary or acquired erythrocytosis and commence our workup by reviewing prior blood counts when available in order to determine the duration of erythrocytosis.

• #47 Retrospective Study of High Hemoglobin Levels in 56 Young Adults | Desnoyers | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/375/332

  The main outcome of this study was to establish the etiological profile of erythrocytosis among the population of young adults at a Canadian university hospital center. […] The 25 cases of absolute erythrocytosis had a secondary etiology. Of these 25 patients, the diagnosis was either clearly identified in the medical records or attributed as most likely after a review of the records by the authors. […] The main conclusion emerging from this study is that erythrocytosis in young adults is predominantly secondary to an external factor that stimulates erythropoiesis. […] This study therefore reveals the lack of structure in the diagnostic approach and follow-up of patients presenting with erythrocytosis when compared with the current recommendations. […] We suggest that modifications be made in the diagnostic approach and management of erythrocytosis in this population. We adapted the current algorithm in light of the results of this study and believe it might better guide clinical decisions in the future.

• #48 JAK2 unmutated erythrocytosis: current diagnostic approach and therapeutic views | Leukemia

  https://www.nature.com/articles/s41375-021-01290-6

  Hereditary erythrocytosis is suspected in children and young adults with long-standing erythrocytosis, particularly with a positive family history. A subnormal serum EPO level is suspicious for the presence of an EPOR mutation. On the other hand, if serum EPO is normal or elevated, we proceed with venous p50 measurement (oxygen tension at which Hgb is 50% saturated). […] In a high proportion (70%) of patients with erythrocytosis, a specific etiology remains elusive despite extensive testing; such cases are often referred to as idiopathic or not otherwise specified. In rare instances, SH2B3/LNK exon 2 mutations or polymorphisms have been reported in patients with unexplained erythrocytosis, with subnormal serum EPO levels, and absence of JAK2, MPL, and EPOR mutations. […] A dearth of compelling evidence defining optimal management strategies for JAK2 unmutated erythrocytosis stems from the heterogeneity in associated hereditary and acquired disorders. Hence, it is common practice to inadvertently extrapolate outcomes from studies conducted in PV patients or follow consensus guidelines. […] In summary, the prompt and accurate distinction between underlying causes is decidedly crucial, as management is directly dictated by etiology, and incorrect diagnosis may lead to undertreatment or overtreatment.

• #49

  https://link.springer.com/article/10.1007/s00277-021-04546-4

  In the second step of the algorithm, clonal erythrocytosis was ruled out and secondary causes were reviewed. […] After a thorough documentation review of all patients secondary erythrocytosis was found in 34/116 (29%) patients, 15/116 (13%) remained idiopathic despite adequate diagnostics, whereas a quite high number of patients, 67/116 (58%) would need further investigations for characterisation of erythrocytosis according to modern diagnostic algorithms. […] The treatment guidelines for non-clonal erythrocytosis are not clear. […] The three-step algorithm is a useful tool for everyday clinical evaluation of erythrocytosis. Secondary causes of erythrocytosis should be systematically checked and IE patients referred for genetic testing. Only patients with known aetiology of erythrocytosis can be properly managed.

• #50 Potential limitations of diagnostic standard codes to distinguish polycythemia vera and secondary erythrocytosis | Scientific Reports

  https://www.nature.com/articles/s41598-022-08606-1

  Red cell overproduction is seen in polycythemia vera (PV), a bone marrow myeloproliferative neoplasm characterized by trilinear cell proliferation (WBC, platelets), as well as in secondary erythrocytosis (SE), a group of heterogeneous disorders characterized by elevated EPO gene transcription. […] We aimed to verify the concordance of the International Classification of Diseases (ICD) code-based diagnosis of polycythemia or erythrocytosis with the true clinical diagnosis of these conditions. […] The reliability of ICD coding was calculated using Cohen’s kappa. […] Remarkably, 11% of the patients had concurrent diagnosis codes for PV and SE and were unable to be classified appropriately without individual chart review. […] The ICD code-based diagnostic system led to misidentification in an important fraction of cases.

• #51 Potential limitations of diagnostic standard codes to distinguish polycythemia vera and secondary erythrocytosis | Scientific Reports

  https://www.nature.com/articles/s41598-022-08606-1

  This represents a problem for the detection of PV or SE cases by ICD-based registries and their derived studies. […] Research based exclusively on ICD codes could have a potential impact on patient care and public health, and limitations must be weighed when research findings are conveyed. […] Erythrocytosis is a common reason for hematology services consultation. […] The prevalence of PV is estimated to be 4755 per 100,000 in the United States. […] Despite the expertise and forward understanding of pathophysiology, for some cases, the classification and management of the disease can be far from straightforward and challenging. […] This implies the use of the international diagnostic classification standard for reporting diseases (ICD codes). […] The introduction of errors at the steps of diagnosis assignment has the potential to introduce systematic mistakes and bias in those types of research studies.

• #52 JAK2 unmutated erythrocytosis: current diagnostic approach and therapeutic views | Leukemia

  https://www.nature.com/articles/s41375-021-01290-6

  In clinical practice, hematology referrals for erythrocytosis are triggered by Hgb/Hct level above 16.5g/dl/49% and 16g/dl/48% in Caucasian males and females, respectively, and should be confirmed by at least two separate blood counts evaluated at different time points. This should be followed by distinguishing true from apparent erythrocytosis; the former is a result of either a clonal MPN, as in PV, or a non-clonal process resulting in secondary erythrocytosis. It is also important to recognize inapparent (masked) erythrocytosis in which an increase in red cell mass (RCM) is accompanied by a concomitant increase in plasma volume and therefore masked by a normal Hgb/Hct. […] Once PV has been conclusively ruled out, we entertain the possibility of either hereditary or acquired erythrocytosis and commence our workup by reviewing prior blood counts when available in order to determine the duration of erythrocytosis.

• #53

  https://journals.lww.com/jaht/fulltext/2023/14020/serum_erythropoietin_in_the_evaluation_of.8.aspx

  Serum erythropoietin (S. EPO) continues to be a minor diagnostic criterion for discriminating polycythemia vera (PV) from other causes of erythrocytosis. However, in the current era of Janus kinase 2 (JAK2) mutation testing, its relevance for establishing the diagnosis of PV is controversial. […] The study aimed to assess the utility of S. EPO in patients with absolute erythrocytosis and ascertain its sensitivity and specificity for establishing the diagnosis of PV. […] Overall, a low sensitivity and specificity of S. EPO were observed for diagnosing PV as an isolated investigation, thus questioning its diagnostic utility, though high levels had an excellent negative predictive value. However, this simple and inexpensive test remains an important screening tool for evaluating patients with absolute erythrocytosis.

• #54

  https://journals.lww.com/jaht/fulltext/2023/14020/serum_erythropoietin_in_the_evaluation_of.8.aspx

  The WHO still includes subnormal levels as minor diagnostic criteria for PV diagnosis. […] In the present study, we observed PV to account for 24.1%, of all erythrocytosis and ~10% of all MPNs at our center. […] The diagnosis of PV largely relies on high Hb levels and JAK2 mutation status. S. EPO levels are supplementary and assist in diagnosis, but the specificity of low S. EPO for diagnosing PV is low. It, however, continues to be an important test parameter in the diagnostic algorithm for differentiating PV from other secondary causes of erythrocytosis, since the normal or high EPO has a high negative predictive value for excluding PV.

• #55 Potential limitations of diagnostic standard codes to distinguish polycythemia vera and secondary erythrocytosis | Scientific Reports

  https://www.nature.com/articles/s41598-022-08606-1

  We aimed to describe the concordance of a ten-year ICD code-based cohort of adult patients consulted to our center with a diagnosis of polycythemia or erythrocytosis (and had testing done for the presence of a JAK2V617F mutation) with the true clinical diagnosis of these conditions, as recorded in the medical records by the evaluating hematologist and supported by the available diagnostic data. […] The most notable finding was that 11% of all cases had concurrent codes for both PV and SE. […] Only through chart review were those cases able to be classified appropriately. […] The Cohens Kappa for PV was 0.544 (weak agreement) and for SE was 0.853 (strong agreement), therefore using only ICD diagnosis information to assess databases may lead to the inclusion of SE cases and introduce sample misclassification.

• #56 Retrospective Study of High Hemoglobin Levels in 56 Young Adults | Desnoyers | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/375/332

  Background: Erythrocytosis is a frequent request for consultation in the hematologic field. The diagnostic approach is well established in the general population but in a young adult, finding the etiology of erythrocytosis can be a real diagnostic challenge. […] Erythrocytosis represents a frequent request for consultation in the hematologic field. Frequently, it is an incidental finding secondary to a persistent elevation of hemoglobin and hematocrit. Erythrocytosis is suspected when repeated values of hemoglobin are above 165 g/L in female and 185 g/L in male, or when hematocrit values exceed 48% in female and 52% in male. However, the term absolute erythrocytosis is used when an erythrocytic mass exceeds 125% of the predicted value. […] Erythrocytosis is subsequently classified according to its etiology, whether primary or secondary. Primary erythrocytosis is due to a direct defect within the red blood cell (RBC) progenitors. Secondary erythrocytosis is due to external factors stimulating the RBC production. The latter type is more common in the general population. Its differential diagnosis is broad and encompasses notably cardio-pulmonary pathologies, smoking and exogenous androgens.

• #57 Retrospective Study of High Hemoglobin Levels in 56 Young Adults | Desnoyers | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/375/332

  The main outcome of this study was to establish the etiological profile of erythrocytosis among the population of young adults at a Canadian university hospital center. […] The 25 cases of absolute erythrocytosis had a secondary etiology. Of these 25 patients, the diagnosis was either clearly identified in the medical records or attributed as most likely after a review of the records by the authors. […] The main conclusion emerging from this study is that erythrocytosis in young adults is predominantly secondary to an external factor that stimulates erythropoiesis. […] This study therefore reveals the lack of structure in the diagnostic approach and follow-up of patients presenting with erythrocytosis when compared with the current recommendations. […] We suggest that modifications be made in the diagnostic approach and management of erythrocytosis in this population. We adapted the current algorithm in light of the results of this study and believe it might better guide clinical decisions in the future.

• #58 Diagnosis and management of congenital and idiopathic erythrocytosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3627324/

  Once all the causes of primary and secondary erythrocytosis have been considered, there remains a group for which no cause for the erythrocytosis can be identified. This group is in a category termed idiopathic erythrocytosis. […] The management of a congenital or idiopathic erythrocytosis is much more problematic as there is little evidence available for guidance. […] The therapeutic options for a patient with congenital and erythrocytosis are limited and largely of unproven efficacy. Low-dose aspirin in those without a specific contraindication and venesection to an achievable target HCT are the main treatments to be considered.

• #59 Diagnosis and Evaluation in Polycythemia Vera

  https://www.onclive.com/view/diagnosis-and-evaluation-in-polycythemia-vera

  The WHO criteria, once you prove erythrocytosis, want you to establish a diagnostic molecular marker such as the JAK2, and look at the bone marrow for the typical histological features as it relates to erythroid precursors, hypercellularity, and others consistent with P vera. […] Additionally, there are minor criteria that can be considered, such as a suboptimal EPO level, if an individual lacks either of the 2 JAK2 mutations. There are individuals who have JAK2-negative P vera, but this is not common in a diagnosis of an exclusion and typically need a solid case that bone marrow, low EPO, and others help establish. […] Cytoreductive therapy would be controlling hematocrit, white cells, and platelets. In that case, were talking about complete hematologic response. The follow-up is similar in a low- or high-risk patient. The goals are well defined and built in to our NCCN [National Comprehensive Cancer Network] Guidelines.

• #60 Polycythemia/Erythrocytosis • MSPCA-Angell

  https://www.mspca.org/angell_services/24386-2/

  Primary erythrocytosis is defined as cases in which increased erythropoiesis is not due to an increase in EPO. […] Secondary erythrocytosis is defined as cases in which increased erythropoiesis is due to an increase in EPO. […] Most clinical signs of absolute erythrocytosis are related to an increase in blood viscosity. […] It is crucial to distinguish relative erythrocytosis from absolute erythrocytosis, as the treatment varies significantly. […] If the underlying cause for erythrocytosis can be corrected, it should be treated (i.e. removal of an EPO secreting tumor, prevention of carbon monoxide exposure). […] As erythrocytosis is a rarely diagnosed condition, there is a scarcity of data regarding survival. In general, the prognosis for patients with primary erythrocytosis is guarded, whereas the prognosis for patients with secondary erythrocytosis depends on the underlying cause.

• #61 Diagnosis and management of congenital and idiopathic erythrocytosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3627324/

  Once all the causes of primary and secondary erythrocytosis have been considered, there remains a group for which no cause for the erythrocytosis can be identified. This group is in a category termed idiopathic erythrocytosis. […] The management of a congenital or idiopathic erythrocytosis is much more problematic as there is little evidence available for guidance. […] The therapeutic options for a patient with congenital and erythrocytosis are limited and largely of unproven efficacy. Low-dose aspirin in those without a specific contraindication and venesection to an achievable target HCT are the main treatments to be considered.

• #62

  https://link.springer.com/article/10.1007/s10238-023-01283-y

  Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). […] We demonstrated that most of our cohort (40/56: 71.4%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. […] Once all the causes of primary and secondary erythrocytosis have been considered, there remains a group for which no cause can be identified. This condition is known as idiopathic erythrocytosis (IE). The frequency of IE has been estimated to be 1.1 per 1000 subjects, which is higher than that observed in PV. […] Evidence is lacking to define best management, but aspirin and venesection to a target Hct should be considered. Cytoreductive therapy, to date, is not appropriate for the treatment of patients with erythrocytosis in whom there is no evidence of a malignant clone.

• #63 JAK2 unmutated erythrocytosis: current diagnostic approach and therapeutic views | Leukemia

  https://www.nature.com/articles/s41375-021-01290-6

  Hereditary erythrocytosis is suspected in children and young adults with long-standing erythrocytosis, particularly with a positive family history. A subnormal serum EPO level is suspicious for the presence of an EPOR mutation. On the other hand, if serum EPO is normal or elevated, we proceed with venous p50 measurement (oxygen tension at which Hgb is 50% saturated). […] In a high proportion (70%) of patients with erythrocytosis, a specific etiology remains elusive despite extensive testing; such cases are often referred to as idiopathic or not otherwise specified. In rare instances, SH2B3/LNK exon 2 mutations or polymorphisms have been reported in patients with unexplained erythrocytosis, with subnormal serum EPO levels, and absence of JAK2, MPL, and EPOR mutations. […] A dearth of compelling evidence defining optimal management strategies for JAK2 unmutated erythrocytosis stems from the heterogeneity in associated hereditary and acquired disorders. Hence, it is common practice to inadvertently extrapolate outcomes from studies conducted in PV patients or follow consensus guidelines. […] In summary, the prompt and accurate distinction between underlying causes is decidedly crucial, as management is directly dictated by etiology, and incorrect diagnosis may lead to undertreatment or overtreatment.

• #64 Diagnosis and management of congenital and idiopathic erythrocytosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3627324/

  Once all the causes of primary and secondary erythrocytosis have been considered, there remains a group for which no cause for the erythrocytosis can be identified. This group is in a category termed idiopathic erythrocytosis. […] The management of a congenital or idiopathic erythrocytosis is much more problematic as there is little evidence available for guidance. […] The therapeutic options for a patient with congenital and erythrocytosis are limited and largely of unproven efficacy. Low-dose aspirin in those without a specific contraindication and venesection to an achievable target HCT are the main treatments to be considered.

• #65

  https://link.springer.com/article/10.1007/s00277-021-04546-4

  In the second step of the algorithm, clonal erythrocytosis was ruled out and secondary causes were reviewed. […] After a thorough documentation review of all patients secondary erythrocytosis was found in 34/116 (29%) patients, 15/116 (13%) remained idiopathic despite adequate diagnostics, whereas a quite high number of patients, 67/116 (58%) would need further investigations for characterisation of erythrocytosis according to modern diagnostic algorithms. […] The treatment guidelines for non-clonal erythrocytosis are not clear. […] The three-step algorithm is a useful tool for everyday clinical evaluation of erythrocytosis. Secondary causes of erythrocytosis should be systematically checked and IE patients referred for genetic testing. Only patients with known aetiology of erythrocytosis can be properly managed.

• #66 JAK2 unmutated erythrocytosis: current diagnostic approach and therapeutic views | Leukemia

  https://www.nature.com/articles/s41375-021-01290-6

  Hereditary erythrocytosis is suspected in children and young adults with long-standing erythrocytosis, particularly with a positive family history. A subnormal serum EPO level is suspicious for the presence of an EPOR mutation. On the other hand, if serum EPO is normal or elevated, we proceed with venous p50 measurement (oxygen tension at which Hgb is 50% saturated). […] In a high proportion (70%) of patients with erythrocytosis, a specific etiology remains elusive despite extensive testing; such cases are often referred to as idiopathic or not otherwise specified. In rare instances, SH2B3/LNK exon 2 mutations or polymorphisms have been reported in patients with unexplained erythrocytosis, with subnormal serum EPO levels, and absence of JAK2, MPL, and EPOR mutations. […] A dearth of compelling evidence defining optimal management strategies for JAK2 unmutated erythrocytosis stems from the heterogeneity in associated hereditary and acquired disorders. Hence, it is common practice to inadvertently extrapolate outcomes from studies conducted in PV patients or follow consensus guidelines. […] In summary, the prompt and accurate distinction between underlying causes is decidedly crucial, as management is directly dictated by etiology, and incorrect diagnosis may lead to undertreatment or overtreatment.

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