Materiały źródłowe

• #1 Polycythemia Vera – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK557660/

  Polycythemia vera is a myeloproliferative disorder associated with a Janus kinase-2 (JAK2) mutation that causes the neoplastic proliferation of the hematopoietic progenitor cells. […] The etiology of the disease process appears to be neoplastic proliferation. There is a signaling defect leading to an abnormal response to growth factors, and the abnormal clonal line interferes with normal lineage proliferation. The Janus kinase-2 (JAK2) gene involved with intracellular signaling is mutated in 90% of cases of polycythemia vera (PV). […] Cytogenetic studies show the presence of an abnormal karyotype in the hematopoietic progenitor cells in approximately 34% of patients with PV. At the time of diagnosis, 20% of patients have cytogenetic abnormalities, increasing to more than 80% for those with more than 10 years of follow-up care.

• #2 Polycythemia vera – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/polycythemia-vera/symptoms-causes/syc-20355850

  Polycythemia vera happens when a change in a gene causes a problem with making blood cells. The body typically controls the number of each of the three types of blood cells. These are red blood cells, white blood cells and platelets. But in polycythemia vera, the bone marrow makes too many of some of these blood cells. […] The cause of the gene change in polycythemia vera is unknown. But it’s not passed through families.

• #3 Polycythemia vera – Wikipedia

  https://en.wikipedia.org/wiki/Polycythemia_vera

  In oncology, polycythemia vera (PV) is an uncommon myeloproliferative neoplasm in which the bone marrow makes too many red blood cells. The majority of cases are caused by mutations in the JAK2 gene, most commonly resulting in a single amino acid change in its protein product from valine to phenylalanine at position 617. […] Polycythemia vera (PV), being a primary polycythemia (increase in the fraction of volume occupied by red cells in the blood), is caused by neoplastic proliferation and maturation of erythroid, megakaryocytic and granulocytic elements to produce what is referred to as panmyelosis. In contrast to secondary polycythemias, PV is associated with a low serum level of the hormone erythropoietin (EPO). Instead, PV cells often carry activating mutation in a tyrosine kinase encoding gene, JAK2, which acts in signaling pathways of the EPO receptor, making those cells proliferate independently from EPO.

• #4 Polycythemia Vera – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/polycythemia-vera

  Polycythemia vera is due to mutations in the Janus kinase 2 (JAK2) gene, which produces a protein (enzyme) that stimulates excessive production of blood cells. […] More than 95% of people with polycythemia vera have a mutation in the JAK2 gene. This mutation causes excess blood cell production. […] In addition, mutations in the calreticulin gene (CALR) and other genes have been found in some people with polycythemia vera. These mutations lead to sustained activation of JAK2 kinase, the enzyme that causes excess red blood cell production.

• #5 Polycythemia Vera (PV) – MPN Research Foundation

  https://mpnresearchfoundation.org/polycythemia-vera-pv/

  The trigger for polycythemia vera (PV) and other myeloproliferative neoplasms (MPNs) isnt known. However, researchers have discovered that PV and other MPNs may be caused by non-inherited genetic mutations affecting proteins that work in signaling pathways in cells. […] Nearly all PV patients have a mutation called JAK2V617F (found in the JAK2 gene) in their blood-forming cells. This mutation is one of the ways that JAK (Janus kinase) pathway signaling can become dysregulated and cause the body to produce too many blood cells. […] Approximately 95% of all PV patients have a mutation of the JAK2 gene in their blood-forming cells. This mutation leads to hyperactive JAK (Janus kinase) signaling, causing the body to make the wrong number of blood cells.

• #6 Polycythemia Vera – Hematology and Oncology – Merck Manual Professional Edition

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

  Polycythemia vera is caused by a mutation in an hematopoietic stem cell. […] Mutations of the Janus kinase 2 (JAK2) gene are responsible in most cases of polycythemia vera. […] Specifically, the JAK2V617F mutation or the JAK2 exon12 mutation is present in 95% of patients with polycythemia vera. […] Calreticulin (CALR) mutations have been found rarely in patients with polycythemia vera who lack a JAK2 mutation, and lymphocytic adaptor protein (LNK) mutations have been found in patients with isolated erythrocytosis. […] These mutations lead to sustained activation of the JAK2 kinase, which causes excess blood cell production independent of erythropoietin.

• #7 Polycythemia vera – Wikipedia

  https://en.wikipedia.org/wiki/Polycythemia_vera

  A mutation in the JAK2 kinase (V617F) is strongly associated with polycythemia vera. While it is a JAK2 V617F mutation in 95% of patients, JAK2 exon 12 mutations have also been observed. The V617F mutation is not inherited, but develops as a somatic mutation in the erythroid progenitor cells. Some patients may lose the normal allele in the diseased cells entirely together with the short arm of chromosome 9 (9p), likely due to mitotic recombination causing copy-neutral loss of heterozygosity. While the JAK2 V617F mutation is generally sporadic (random), a certain inherited haplotype of JAK2 has been associated with its development.

• #8

  https://www.texasoncology.com/cancer-blood-disorders/cancer-facts/polycythemia-vera

  Polycythemia vera (PV) is a chronic blood malignancy caused by an acquired gene mutation of the blood-producing cells in the bone marrow which causes an overproduction of blood cells, particularly red blood cells. […] The exact causes of this acquired genetic mutation in polycythemia vera are not yet known. […] Almost all people with PV have a Janus kinase 2 (JAK2) gene mutation. Of these, 95% have a mutation of JAK2 V617F in exon 14, with most of the remainder having mutations in exon 12. […] Risk factors may include the following: Exposure to radiation and toxic substances may increase risk.

• #9 Polycythemia Vera : Symptoms, Causes, Stages, Diagnosis and Treatment

  https://oncodaily.com/oncolibrary/cancer-types/225800

  The primary cause of polycythemia vera (PV) is a mutation in the JAK2 (Janus kinase 2) gene, present in approximately 95% of PV cases (New England Journal of Medicine, 2024). This mutation, known as JAK2 V617F, occurs in the hematopoietic stem cells of the bone marrow. It results in constant activation of the JAK-STAT signaling pathway, which regulates blood cell production. This unchecked signaling causes the overproduction of red blood cells and, in some cases, white blood cells and platelets, leading to increased blood viscosity and the associated risks of clotting and complications. […] Although the JAK2 mutation is the predominant cause, environmental and lifestyle factors may exacerbate the condition. Smoking, for example, has been linked to increased red blood cell counts and a heightened risk of clotting. Chronic exposure to toxins, such as benzene or radiation, may also predispose individuals to myeloproliferative disorders, including PV (Haematologica, 2024). Obesity and cardiovascular risk factors further contribute to complications associated with the disease.

• #10 Dysregulated iron metabolism in polycythemia vera: etiology and consequences | Leukemia

  https://www.nature.com/articles/s41375-018-0207-9

  Polycythemia vera (PV) is a chronic myeloproliferative neoplasm. […] Most patients with PV present with iron deficiency at diagnosis, even prior to the onset of therapeutic phlebotomy, the mainstay of treatment. […] The genesis of iron deficiency in PV and its effect on disease manifestations and natural history have been explored to a limited extent. […] The genetic basis of PV was largely speculative until the discovery of driver mutations involving janus kinase 2 (JAK2). […] The most common JAK2 driver mutation is JAK2 V617F which results in constitutive erythropoietin (Epo)-independent JAK/STAT signaling and upregulation of genes downstream of the JAK/STAT pathway. […] Among patients with MPNs, mutations in exon 12 of JAK2 are found only in PV. […] These findings confirm that JAK2 V617F results in a more PV-like picture among ET patients but raise the question of how a single mutation can result in phenotypic diversity among the MPNs.

• #11 Polycythemia Vera | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0501/p2139.html

  Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell mass. […] Secondary causes of increased red blood cell mass (e.g., heavy smoking, chronic pulmonary disease, renal disease) are more common than polycythemia vera and must be excluded. […] The median age of patients diagnosed with PV is 60 years, although it can occur in persons in all age groups. […] PV occurs with a slight predominance in men. […] The seriousness of PV is underscored by the fact that the median survival in untreated symptomatic patients after diagnosis is six to 18 months. […] Serum erythropoietin (EPO), bone marrow histopathology and karyotype, and the presence of endogenous erythroid colonies (EEC) have been proposed as diagnostic tests for PV. […] Because PV is an autonomous (i.e., EPO-independent) erythroid proliferation, serum EPO levels in PV are low or normal.

• #12 Polycythemia Vera: Practice Essentials, Pathophysiology, Etiology

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

  Cytogenetic studies show the presence of an abnormal karyotype in the hematopoietic progenitor cells in approximately 34% of patients with PV, depending on the stage of the disease in which the study was performed. Approximately 20% of patients have cytogenetic abnormalities at diagnosis, increasing to more than 80% for those with more than 10 years of follow-up care. […] The following genetic abnormalities, which are similar to the abnormal karyotypes observed in patients with myelodysplastic syndromes and other MPDs, have been observed in patients with PV: Deletion of 20q (8.4%), Deletion of 13q (3%), Trisomy 8 (7%), Trisomy 9 (7%), Trisomy of 1q (4%), Deletion of 5q or monosomy 5 (3%), Deletion of 7q or monosomy 7 (1%). […] Spivak and colleagues analyzed gene expression in CD34+ peripheral blood cells from 19 patients with PV and found twice as many up-regulated or down-regulated genes in men as in women. In addition, these researchers found 102 genes with differential regulation that was concordant in men and women and that could be used to divide patients into two phenotypical groups. The groups differed significantly with respect to disease duration, clinical manifestations, and prognosis.

• #13 Polycythemia vera: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/polycythemia-vera/

  Mutations in the JAK2 and TET2 genes are associated with polycythemia vera. […] Although it remains unclear exactly what initiates polycythemia vera, researchers believe that it begins when mutations occur in the DNA of a hematopoietic stem cell. […] JAK2 gene mutations seem to be particularly important for the development of polycythemia vera, as nearly all affected individuals have a mutation in this gene. […] JAK2 gene mutations result in the production of a JAK2 protein that is constantly turned on (constitutively activated), which increases production of blood cells and prolongs their survival. […] The function of the TET2 gene is unknown. […] Although mutations in the TET2 gene have been found in approximately 16 percent of people with polycythemia vera, it is unclear what role these mutations play in the development of the condition.

• #14 Polycythemia vera: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/polycythemia-vera/

  Mutations in the JAK2 and TET2 genes are associated with polycythemia vera. […] Although it remains unclear exactly what initiates polycythemia vera, researchers believe that it begins when mutations occur in the DNA of a hematopoietic stem cell. […] JAK2 gene mutations seem to be particularly important for the development of polycythemia vera, as nearly all affected individuals have a mutation in this gene. […] JAK2 gene mutations result in the production of a JAK2 protein that is constantly turned on (constitutively activated), which increases production of blood cells and prolongs their survival. […] The function of the TET2 gene is unknown. […] Although mutations in the TET2 gene have been found in approximately 16 percent of people with polycythemia vera, it is unclear what role these mutations play in the development of the condition.

• #15 Polycythemia Vera | City of Hope

  https://www.cancercenter.com/blood-cancers/myeloproliferative-neoplasms/polycythemia-vera

  Polycythemia vera (PV) is a rare, slow-growing blood cancer. […] PV typically develops on its own; it isn’t often inherited. Cells in the bone marrow develop genetic mutations that cause PV. Researchers don’t know of any specific reasons that these genetic changes happen. […] Almost everyone with PV has a genetic mutation in the JAK2 gene, which may cause changes in blood stem cells (called hematopoietic stem cells) that lead to polycythemia vera. […] The two specific JAK2 mutations that seem to cause PV are: JAK2 V617F gain-of-function mutation and JAK2 exon 12 mutation. […] The precise role of the JAK2 mutation isn’t fully understood. […] About 16 percent of patients with PV also have a mutation in the TET2 gene, according to the National Library of Medicine. Researchers aren’t sure which role this gene plays.

• #16 Polycythemia Vera – Hematology and Oncology – Merck Manual Professional Edition

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

  Polycythemia vera is caused by a mutation in an hematopoietic stem cell. […] Mutations of the Janus kinase 2 (JAK2) gene are responsible in most cases of polycythemia vera. […] Specifically, the JAK2V617F mutation or the JAK2 exon12 mutation is present in 95% of patients with polycythemia vera. […] Calreticulin (CALR) mutations have been found rarely in patients with polycythemia vera who lack a JAK2 mutation, and lymphocytic adaptor protein (LNK) mutations have been found in patients with isolated erythrocytosis. […] These mutations lead to sustained activation of the JAK2 kinase, which causes excess blood cell production independent of erythropoietin.

• #17 Polycythemia Vera – Hematology and Oncology – Merck Manual Professional Edition

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

  Polycythemia vera is caused by a mutation in an hematopoietic stem cell. […] Mutations of the Janus kinase 2 (JAK2) gene are responsible in most cases of polycythemia vera. […] Specifically, the JAK2V617F mutation or the JAK2 exon12 mutation is present in 95% of patients with polycythemia vera. […] Calreticulin (CALR) mutations have been found rarely in patients with polycythemia vera who lack a JAK2 mutation, and lymphocytic adaptor protein (LNK) mutations have been found in patients with isolated erythrocytosis. […] These mutations lead to sustained activation of the JAK2 kinase, which causes excess blood cell production independent of erythropoietin.

• #18 Polycythemia Vera – Hematology and Oncology – Merck Manual Professional Edition

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

  Polycythemia vera is caused by a mutation in an hematopoietic stem cell. […] Mutations of the Janus kinase 2 (JAK2) gene are responsible in most cases of polycythemia vera. […] Specifically, the JAK2V617F mutation or the JAK2 exon12 mutation is present in 95% of patients with polycythemia vera. […] Calreticulin (CALR) mutations have been found rarely in patients with polycythemia vera who lack a JAK2 mutation, and lymphocytic adaptor protein (LNK) mutations have been found in patients with isolated erythrocytosis. […] These mutations lead to sustained activation of the JAK2 kinase, which causes excess blood cell production independent of erythropoietin.

• #19 Polycythemia Vera: Practice Essentials, Pathophysiology, Etiology

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

  Cytogenetic studies show the presence of an abnormal karyotype in the hematopoietic progenitor cells in approximately 34% of patients with PV, depending on the stage of the disease in which the study was performed. Approximately 20% of patients have cytogenetic abnormalities at diagnosis, increasing to more than 80% for those with more than 10 years of follow-up care. […] The following genetic abnormalities, which are similar to the abnormal karyotypes observed in patients with myelodysplastic syndromes and other MPDs, have been observed in patients with PV: Deletion of 20q (8.4%), Deletion of 13q (3%), Trisomy 8 (7%), Trisomy 9 (7%), Trisomy of 1q (4%), Deletion of 5q or monosomy 5 (3%), Deletion of 7q or monosomy 7 (1%). […] Spivak and colleagues analyzed gene expression in CD34+ peripheral blood cells from 19 patients with PV and found twice as many up-regulated or down-regulated genes in men as in women. In addition, these researchers found 102 genes with differential regulation that was concordant in men and women and that could be used to divide patients into two phenotypical groups. The groups differed significantly with respect to disease duration, clinical manifestations, and prognosis.

• #20 Polycythemia Vera – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK557660/

  Polycythemia vera is a myeloproliferative disorder associated with a Janus kinase-2 (JAK2) mutation that causes the neoplastic proliferation of the hematopoietic progenitor cells. […] The etiology of the disease process appears to be neoplastic proliferation. There is a signaling defect leading to an abnormal response to growth factors, and the abnormal clonal line interferes with normal lineage proliferation. The Janus kinase-2 (JAK2) gene involved with intracellular signaling is mutated in 90% of cases of polycythemia vera (PV). […] Cytogenetic studies show the presence of an abnormal karyotype in the hematopoietic progenitor cells in approximately 34% of patients with PV. At the time of diagnosis, 20% of patients have cytogenetic abnormalities, increasing to more than 80% for those with more than 10 years of follow-up care.

• #21 Polycythemia Vera: Practice Essentials, Pathophysiology, Etiology

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

  Cytogenetic studies show the presence of an abnormal karyotype in the hematopoietic progenitor cells in approximately 34% of patients with PV, depending on the stage of the disease in which the study was performed. Approximately 20% of patients have cytogenetic abnormalities at diagnosis, increasing to more than 80% for those with more than 10 years of follow-up care. […] The following genetic abnormalities, which are similar to the abnormal karyotypes observed in patients with myelodysplastic syndromes and other MPDs, have been observed in patients with PV: Deletion of 20q (8.4%), Deletion of 13q (3%), Trisomy 8 (7%), Trisomy 9 (7%), Trisomy of 1q (4%), Deletion of 5q or monosomy 5 (3%), Deletion of 7q or monosomy 7 (1%). […] Spivak and colleagues analyzed gene expression in CD34+ peripheral blood cells from 19 patients with PV and found twice as many up-regulated or down-regulated genes in men as in women. In addition, these researchers found 102 genes with differential regulation that was concordant in men and women and that could be used to divide patients into two phenotypical groups. The groups differed significantly with respect to disease duration, clinical manifestations, and prognosis.

• #22 Polycythemia Vera: Practice Essentials, Pathophysiology, Etiology

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

  Cytogenetic studies show the presence of an abnormal karyotype in the hematopoietic progenitor cells in approximately 34% of patients with PV, depending on the stage of the disease in which the study was performed. Approximately 20% of patients have cytogenetic abnormalities at diagnosis, increasing to more than 80% for those with more than 10 years of follow-up care. […] The following genetic abnormalities, which are similar to the abnormal karyotypes observed in patients with myelodysplastic syndromes and other MPDs, have been observed in patients with PV: Deletion of 20q (8.4%), Deletion of 13q (3%), Trisomy 8 (7%), Trisomy 9 (7%), Trisomy of 1q (4%), Deletion of 5q or monosomy 5 (3%), Deletion of 7q or monosomy 7 (1%). […] Spivak and colleagues analyzed gene expression in CD34+ peripheral blood cells from 19 patients with PV and found twice as many up-regulated or down-regulated genes in men as in women. In addition, these researchers found 102 genes with differential regulation that was concordant in men and women and that could be used to divide patients into two phenotypical groups. The groups differed significantly with respect to disease duration, clinical manifestations, and prognosis.

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

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

  Polycythemia vera occurs in your bone marrow, the soft, spongy material at the center of your bones. This is where new blood cells grow. PV begins when a single gene within a single stem cell in the bone marrow malfunctions. More than 90% of the time, its a gene called JAK2. The mutated gene gives instructions to the stem cell to continually reproduce itself. All of the reproduced cells also continue to reproduce, until the abnormal cells crowd out the normal cells in your bone marrow. Most of the time, the JAK2 gene mutation is acquired, which means it isnt inherited from a family member. It occurs for unknown reasons sometime during your life. But there have been a few documented cases of multiple family members developing polycythemia vera. […] A gene mutation that occurs for unknown reasons, usually sometime during the course of your life, causes polycythemia vera.

• #24 Polycythemia Vera: Symptoms, Causes, Treatments

  https://www.webmd.com/cancer/polycythemia-vera-causes-symptoms

  Doctors dont know what causes polycythemia vera. Anyone can get PV, but its usually seen in people over 60. Men are a little more likely than women to get it. […] While the cause isnt clear, most people with PV have a problem in a gene called JAK2. Your bone marrow — the spongy center part of your bone — creates your blood cells. Normally, it makes just the right amount. But if your JAK2 gene doesnt work right, your bone marrow makes too many red blood cells. […] Even though the problem is in a gene, you dont get PV from your parents. The gene changes at some point after you’re born, but doctors dont know why.

• #25 What Causes Polycythemia Vera? | Hematology-Oncology Associates of CNY

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

  Polycythemia vera (PV) also is known as primary polycythemia. A mutation, or change, in the body’s JAK2 gene is the main cause of PV. […] What causes the change in the JAK2 gene isn’t known. PV generally isn’t inheritedthat is, passed from parents to children through genes. However, in some families, the JAK2 gene may have a tendency to mutate. Other, unknown genetic factors also may play a role in causing PV. […] Another type of polycythemia, called secondary polycythemia, isn’t related to the JAK2 gene. Long-term exposure to low oxygen levels causes secondary polycythemia. […] A lack of oxygen over a long period can cause your body to make more of the hormone erythropoietin (EPO). High levels of EPO can prompt your body to make more red blood cells than normal. This leads to thicker blood, as seen in PV. […] Rarely, tumors can make and release EPO, or certain blood problems can cause the body to make more EPO.

• #26 Clinical manifestations and diagnosis of polycythemia vera – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-polycythemia-vera

  Polycythemia vera (PV, polycythemia rubra vera, maladie de Vaquez) is one of the chronic myeloproliferative neoplasms (MPNs), which are collectively characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. PV is distinguished clinically from the other MPNs by the presence of an elevated red blood cell mass. However, an increased red blood cell mass alone is insufficient to establish the diagnosis, since this is also observed in conditions associated with chronic hypoxia and with erythropoietin-secreting tumors. […] While there is no known familial disposition to PV, rare families have been described in which multiple members develop myeloproliferative neoplasms, including PV. Studies of these families suggest the presence of an autosomal dominant mutation that may predispose to acquisition of a secondary somatic mutation such as a JAK2 mutation.

• #27 Polycythemia Vera | City of Hope

  https://www.cancercenter.com/blood-cancers/myeloproliferative-neoplasms/polycythemia-vera

  In rare cases, some people inherit an increased risk of developing PV from their families. PV is passed down in an autosomal dominant manner, which means a person with one copy of the mutated gene is at an increased risk of the disease, and his or her offspring usually has a 50/50 chance of inheriting the broken gene. If these offspring acquire the gene, they have an increased risk of developing PV. This inheritance characteristic indicates a gene mutation that increases the risk, but researchers are unsure of which gene it develops in.

• #28 What is polycythameia vera? | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/polycythaemia-vera/what-is-pv

  We know from research that more than 95 out of 100 people (more than 95%) who have polycythaemia vera have a change in the JAK2 gene. A fault in the JACK2 gene occurs in myeloproliferative neoplasms (MPNs). […] The JAK2 gene makes a protein that controls how many blood cells the stem cells make. The fault with your JAK2 gene means the stem cells can start producing red blood cells when they’re not meant to. This results in too many red cells being produced. […] In most cases, these genetic faults happen during a persons lifetime. You are not born with them, so you cant pass them on to your children. […] In rarer cases, you might have a history of myeloproliferative neoplasms in your family. This might mean there is a faulty gene in your family that increases your risk of developing MPNs.

• #29 Polycythemia vera – Wikipedia

  https://en.wikipedia.org/wiki/Polycythemia_vera

  A mutation in the JAK2 kinase (V617F) is strongly associated with polycythemia vera. While it is a JAK2 V617F mutation in 95% of patients, JAK2 exon 12 mutations have also been observed. The V617F mutation is not inherited, but develops as a somatic mutation in the erythroid progenitor cells. Some patients may lose the normal allele in the diseased cells entirely together with the short arm of chromosome 9 (9p), likely due to mitotic recombination causing copy-neutral loss of heterozygosity. While the JAK2 V617F mutation is generally sporadic (random), a certain inherited haplotype of JAK2 has been associated with its development.

• #30 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. […] Nonmodifiable risk factors for PV include older age, male sex, White race, and European descent. […] Modifiable risk factors for PV include smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia. […] Smoking cessation decreases the risk of thrombosis. […] Currently, no medications have been shown to cure the disease or to reduce the risk of conversion to leukemia and myelofibrosis. […] Poor prognostic features include age older than 60 years, history of thrombosis, leukocytosis, high JAK2 burden, abnormal karyotype, and established cardiovascular risk factors such as smoking, hypertension, diabetes, obesity, and hyperlipidemia. […] Without treatment, death typically occurs within two years, mostly from thrombotic events. […] The risk of blast transformation to acute myeloid leukemia or myelodysplastic syndrome over 15 years is 5.5% to 18.7%. […] Progression to myelofibrosis over 15 years is 6% to 14%.

• #31 Polycythemia Vera | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0501/p2139.html

  Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell mass. […] Secondary causes of increased red blood cell mass (e.g., heavy smoking, chronic pulmonary disease, renal disease) are more common than polycythemia vera and must be excluded. […] The median age of patients diagnosed with PV is 60 years, although it can occur in persons in all age groups. […] PV occurs with a slight predominance in men. […] The seriousness of PV is underscored by the fact that the median survival in untreated symptomatic patients after diagnosis is six to 18 months. […] Serum erythropoietin (EPO), bone marrow histopathology and karyotype, and the presence of endogenous erythroid colonies (EEC) have been proposed as diagnostic tests for PV. […] Because PV is an autonomous (i.e., EPO-independent) erythroid proliferation, serum EPO levels in PV are low or normal.

• #32 Polycythaemia (Rubra) Vera – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/myeloproliferative-neoplasms/polycythaemia-rubra-vera/

  Polycythaemia (Rubra) Vera, also known as primary polycythaemia vera, is a disorder where too many red cells are produced in the bone marrow, without any identifiable cause. […] Polycythaemia vera is a rare chronic disease diagnosed in an estimated 2 to 3 people per 100,000 population. […] Polycythaemia vera usually affects older people, with most patients diagnosed over the age of 55. […] Polycythaemia vera may be diagnosed when the red cell mass is 25% greater than the average normal expected value. […] JAK2 mutations (particularly the V617F mutation) can be found in more than 95% of people with Polycythaemia vera. […] In polycythaemia vera the bone marrow is often very active with abnormally high numbers of normal cells. […] Myelosuppressive (bone marrow suppressing) drugs, chemotherapy, biotherapy, radioactive isotopes, cytokines and anticoagulant (anti clotting) drugs are commonly used to reduce blood cell production in the bone marrow. […] In around 10% of all cases, polycythaemia vera transforms over time into another type of myeloproliferative neoplasm called myelofibrosis, and less commonly, in up to 3% of cases into acute myeloid leukaemia.

• #33 Polycythemia Vera: Symptoms, Causes, and Diagnosis

  https://www.healthline.com/health/polycythemia-vera

  Polycythemia vera occurs more often in men than in women. Youre more likely to get PV after age 60, but it can start at any age. […] Mutations (changes) to the JAK2 gene are the main cause of the disease. This gene controls the production of a protein that helps make blood cells. About 95% of people with PV have this type of mutation. […] The mutation that causes PV can be passed down through families. But more often, it can happen without any family connection. Research is ongoing into the cause of the genetic mutation behind PV. […] If you have PV, your risk for developing serious complications depends on how likely you are to develop a blood clot. Factors that can increase your risk of developing blood clots in PV include: a history of blood clots, being over age 60, high blood pressure, diabetes, smoking, high cholesterol, pregnancy. […] Blood thats thicker than normal can always increase your risk of blood clots, no matter the cause.

• #34 Polycythemia Vera | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0501/p2139.html

  Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell mass. […] Secondary causes of increased red blood cell mass (e.g., heavy smoking, chronic pulmonary disease, renal disease) are more common than polycythemia vera and must be excluded. […] The median age of patients diagnosed with PV is 60 years, although it can occur in persons in all age groups. […] PV occurs with a slight predominance in men. […] The seriousness of PV is underscored by the fact that the median survival in untreated symptomatic patients after diagnosis is six to 18 months. […] Serum erythropoietin (EPO), bone marrow histopathology and karyotype, and the presence of endogenous erythroid colonies (EEC) have been proposed as diagnostic tests for PV. […] Because PV is an autonomous (i.e., EPO-independent) erythroid proliferation, serum EPO levels in PV are low or normal.

• #35 Polycythaemia vera | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/polycythaemia-vera

  Polycythaemia vera is caused by abnormal functioning of the bone marrow, but the reason for this remains unknown. […] The reasons for this are unknown. Many of the extra blood cells are also abnormal. Since polycythaemia vera is more common among people with Jewish ancestry, a genetic link could be involved.

• #36 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. […] Nonmodifiable risk factors for PV include older age, male sex, White race, and European descent. […] Modifiable risk factors for PV include smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia. […] Smoking cessation decreases the risk of thrombosis. […] Currently, no medications have been shown to cure the disease or to reduce the risk of conversion to leukemia and myelofibrosis. […] Poor prognostic features include age older than 60 years, history of thrombosis, leukocytosis, high JAK2 burden, abnormal karyotype, and established cardiovascular risk factors such as smoking, hypertension, diabetes, obesity, and hyperlipidemia. […] Without treatment, death typically occurs within two years, mostly from thrombotic events. […] The risk of blast transformation to acute myeloid leukemia or myelodysplastic syndrome over 15 years is 5.5% to 18.7%. […] Progression to myelofibrosis over 15 years is 6% to 14%.

• #37 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. […] Nonmodifiable risk factors for PV include older age, male sex, White race, and European descent. […] Modifiable risk factors for PV include smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia. […] Smoking cessation decreases the risk of thrombosis. […] Currently, no medications have been shown to cure the disease or to reduce the risk of conversion to leukemia and myelofibrosis. […] Poor prognostic features include age older than 60 years, history of thrombosis, leukocytosis, high JAK2 burden, abnormal karyotype, and established cardiovascular risk factors such as smoking, hypertension, diabetes, obesity, and hyperlipidemia. […] Without treatment, death typically occurs within two years, mostly from thrombotic events. […] The risk of blast transformation to acute myeloid leukemia or myelodysplastic syndrome over 15 years is 5.5% to 18.7%. […] Progression to myelofibrosis over 15 years is 6% to 14%.

• #38 Polycythemia Vera: Facts and Statistics

  https://www.verywellhealth.com/facts-about-polycythemia-vera-5704078

  Polycythemia vera is a blood cell disorder that causes the body to make too many blood cells. […] People who have polycythemia vera have an overproduction of red blood cells in the bone marrow. This can occur due to several Janus kinase 2 (JAK2) gene mutations. This gene is involved in regulating the production of blood cells. The mutation is not usually inherited; it can occur spontaneously. […] Some health conditions can increase the risk of polycythemia vera. These include autoimmune diseases (in which a person’s immune system mistakenly attacks their own tissues), bone marrow cancer, and treatment for bone marrow cancer. […] Additionally, certain lifestyle factors and environmental exposures are associated with an increased risk of polycythemia vera. […] Certain toxins may trigger damage in a person’s DNA, causing the mutation that leads to polycythemia vera. These toxins may be inhaled or may come into contact with the skin, such as during work.

• #39 Polycythemia Vera : Symptoms, Causes, Stages, Diagnosis and Treatment

  https://oncodaily.com/oncolibrary/cancer-types/225800

  The primary cause of polycythemia vera (PV) is a mutation in the JAK2 (Janus kinase 2) gene, present in approximately 95% of PV cases (New England Journal of Medicine, 2024). This mutation, known as JAK2 V617F, occurs in the hematopoietic stem cells of the bone marrow. It results in constant activation of the JAK-STAT signaling pathway, which regulates blood cell production. This unchecked signaling causes the overproduction of red blood cells and, in some cases, white blood cells and platelets, leading to increased blood viscosity and the associated risks of clotting and complications. […] Although the JAK2 mutation is the predominant cause, environmental and lifestyle factors may exacerbate the condition. Smoking, for example, has been linked to increased red blood cell counts and a heightened risk of clotting. Chronic exposure to toxins, such as benzene or radiation, may also predispose individuals to myeloproliferative disorders, including PV (Haematologica, 2024). Obesity and cardiovascular risk factors further contribute to complications associated with the disease.

• #40 Polycythemia vera and its neurologic manifestations | MedLink Neurology

  https://www.medlink.com/articles/polycythemia-vera-and-its-neurologic-manifestations

  Polycythemia vera is the commonest of chronic myeloproliferative disorders, which are a group of bone marrow stem cell neoplasms characterized by an autonomous expansion of the cellular elements of the marrow and the peripheral blood. […] The causes of neurologic (and other) complications are increased blood viscosity and associated coagulopathy. […] The etiology of polycythemia vera is unknown, but exposure to benzene, petroleum products, and radiation has been associated with a higher risk of polycythemia vera. […] Polycythemia vera is a clonal myeloproliferative disorder originating from a hematopoietic stem cell in the bone marrow. […] Genomic studies of polycythemia and related myeloproliferative disorders have identified a mutation in the genetic sequence of a specific tyrosine kinase called Janus kinase 2 (JAK2) that induces a growth factor-independent proliferation of cell lines and leads to unregulated hematopoiesis.

• #41 Polycythemia vera and its neurologic manifestations | MedLink Neurology

  https://www.medlink.com/articles/polycythemia-vera-and-its-neurologic-manifestations

  Polycythemia vera is the commonest of chronic myeloproliferative disorders, which are a group of bone marrow stem cell neoplasms characterized by an autonomous expansion of the cellular elements of the marrow and the peripheral blood. […] The causes of neurologic (and other) complications are increased blood viscosity and associated coagulopathy. […] The etiology of polycythemia vera is unknown, but exposure to benzene, petroleum products, and radiation has been associated with a higher risk of polycythemia vera. […] Polycythemia vera is a clonal myeloproliferative disorder originating from a hematopoietic stem cell in the bone marrow. […] Genomic studies of polycythemia and related myeloproliferative disorders have identified a mutation in the genetic sequence of a specific tyrosine kinase called Janus kinase 2 (JAK2) that induces a growth factor-independent proliferation of cell lines and leads to unregulated hematopoiesis.

• #42

  https://www.texasoncology.com/cancer-blood-disorders/cancer-facts/polycythemia-vera

  Polycythemia vera (PV) is a chronic blood malignancy caused by an acquired gene mutation of the blood-producing cells in the bone marrow which causes an overproduction of blood cells, particularly red blood cells. […] The exact causes of this acquired genetic mutation in polycythemia vera are not yet known. […] Almost all people with PV have a Janus kinase 2 (JAK2) gene mutation. Of these, 95% have a mutation of JAK2 V617F in exon 14, with most of the remainder having mutations in exon 12. […] Risk factors may include the following: Exposure to radiation and toxic substances may increase risk.

• #43 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. […] Nonmodifiable risk factors for PV include older age, male sex, White race, and European descent. […] Modifiable risk factors for PV include smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia. […] Smoking cessation decreases the risk of thrombosis. […] Currently, no medications have been shown to cure the disease or to reduce the risk of conversion to leukemia and myelofibrosis. […] Poor prognostic features include age older than 60 years, history of thrombosis, leukocytosis, high JAK2 burden, abnormal karyotype, and established cardiovascular risk factors such as smoking, hypertension, diabetes, obesity, and hyperlipidemia. […] Without treatment, death typically occurs within two years, mostly from thrombotic events. […] The risk of blast transformation to acute myeloid leukemia or myelodysplastic syndrome over 15 years is 5.5% to 18.7%. […] Progression to myelofibrosis over 15 years is 6% to 14%.

• #44 Polycythemia Vera: Facts and Statistics

  https://www.verywellhealth.com/facts-about-polycythemia-vera-5704078

  Polycythemia vera is a blood cell disorder that causes the body to make too many blood cells. […] People who have polycythemia vera have an overproduction of red blood cells in the bone marrow. This can occur due to several Janus kinase 2 (JAK2) gene mutations. This gene is involved in regulating the production of blood cells. The mutation is not usually inherited; it can occur spontaneously. […] Some health conditions can increase the risk of polycythemia vera. These include autoimmune diseases (in which a person’s immune system mistakenly attacks their own tissues), bone marrow cancer, and treatment for bone marrow cancer. […] Additionally, certain lifestyle factors and environmental exposures are associated with an increased risk of polycythemia vera. […] Certain toxins may trigger damage in a person’s DNA, causing the mutation that leads to polycythemia vera. These toxins may be inhaled or may come into contact with the skin, such as during work.

• #45 Polycythemia Vera – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK557660/

  Polycythemia vera is a myeloproliferative disorder associated with a Janus kinase-2 (JAK2) mutation that causes the neoplastic proliferation of the hematopoietic progenitor cells. […] The etiology of the disease process appears to be neoplastic proliferation. There is a signaling defect leading to an abnormal response to growth factors, and the abnormal clonal line interferes with normal lineage proliferation. The Janus kinase-2 (JAK2) gene involved with intracellular signaling is mutated in 90% of cases of polycythemia vera (PV). […] Cytogenetic studies show the presence of an abnormal karyotype in the hematopoietic progenitor cells in approximately 34% of patients with PV. At the time of diagnosis, 20% of patients have cytogenetic abnormalities, increasing to more than 80% for those with more than 10 years of follow-up care.

• #46 Polycythemia vera: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000589.htm

  Polycythemia vera (PV) is a bone marrow disease that leads to an abnormal increase in the number of blood cells. The red blood cells are the most affected blood cell type. […] PV is a disorder of the bone marrow. It mainly causes too many red blood cells to be produced. The numbers of white blood cells and platelets may also be higher than normal. […] The problem is often linked to a gene defect called JAK2V617F. The cause of this gene defect is unknown. This gene defect is not an inherited disorder.

• #47 Orphanet: Polycythemia vera

  https://www.orpha.net/en/disease/detail/729

  PV is associated in 95% of cases with a somatic mutation (JAK2 V617F) in exon 14 of the JAK2 gene (9p24) and, less frequently, a somatic mutation in exon 12 of JAK2, resulting in the uncontrolled activation of the JAK/STAT signaling pathway (proliferation and maturation of hematopoietic cells). […] This leads to blood hyperviscosity due to increased RBCM impairing microcirculation, increased spleen volume, and systemic inflammation.

• #48 Polycythemia Vera-Associated Complications: Pathogenesis, Clinical Man | JBM

  https://www.dovepress.com/polycythemia-vera-associated-complications-pathogenesis-clinical-manif-peer-reviewed-fulltext-article-JBM

  Polycythemia vera is a Philadelphia-negative chronic myeloproliferative neoplasm, characterized by erythrocytosis, which is unique, compared to essential thrombocytosis and primary myelofibrosis. […] Three key driver mutations have been subsequently described in MPNs JAK2, CALR and MPL all of which act to constitutively activate the JAK-STAT pathway. […] JAK2 V617F is most prevalent in PV, compared to ET and PMF (99% vs 60%). […] Thrombosis has multifactorial contributors, including but not limited to gender, and inflammatory stress; investigators have recently hypothesized that microparticles and Neutrophil Extracellular Trap Formations may add to thrombotic burden. […] Some of the well-established risk factors for PV-associated thrombosis include advanced age, disease duration, prior history of thrombosis, erythrocytosis, leukocytosis, and JAK2 V617F allele burden.

• #49 What Causes Polycythemia Vera (PV)? | VoicesOfMPN.com

  https://www.voicesofmpn.com/polycythemia-vera-causes

  Polycythemia vera (PV) is complex and may have many contributing factors. Scientists think that it may be related to changes in certain genes. These changes are called mutations. […] In most people with PV, mutations may cause the bone marrow to make an abnormal number of red blood cells. This imbalance of blood cells may cause some of the symptoms associated with PV. […] Another cause of symptoms may be the overproduction of certain proteins called cytokines. Cytokines can cause inflammation. When your body has too many of these cytokines, you may experience itching, night sweats, and some other symptoms of PV. […] Your Healthcare Professional may do a blood test to see if you have a mutation that may cause PV.

• #50 Polycythemia vera and its neurologic manifestations | MedLink Neurology

  https://www.medlink.com/articles/polycythemia-vera-and-its-neurologic-manifestations

  The neurologic complications of polycythemia result primarily from the hyperviscosity of blood due to increased red blood cell mass, and the main consequence of hyperviscosity is thromboembolism; hyperviscosity-induced thromboembolism may be venous or arterial and is seen in about a third of the patients.

• #51 Dysregulated iron metabolism in polycythemia vera: etiology and consequences | Leukemia

  https://www.nature.com/articles/s41375-018-0207-9

  Polycythemia vera (PV) is a chronic myeloproliferative neoplasm. […] Most patients with PV present with iron deficiency at diagnosis, even prior to the onset of therapeutic phlebotomy, the mainstay of treatment. […] The genesis of iron deficiency in PV and its effect on disease manifestations and natural history have been explored to a limited extent. […] The genetic basis of PV was largely speculative until the discovery of driver mutations involving janus kinase 2 (JAK2). […] The most common JAK2 driver mutation is JAK2 V617F which results in constitutive erythropoietin (Epo)-independent JAK/STAT signaling and upregulation of genes downstream of the JAK/STAT pathway. […] Among patients with MPNs, mutations in exon 12 of JAK2 are found only in PV. […] These findings confirm that JAK2 V617F results in a more PV-like picture among ET patients but raise the question of how a single mutation can result in phenotypic diversity among the MPNs.

• #52 Dysregulated iron metabolism in polycythemia vera: etiology and consequences | Leukemia

  https://www.nature.com/articles/s41375-018-0207-9

  The primary goals of treating PV patients are to ameliorate symptoms, reduce the risk of thrombosis, and prevent transformation to MF and/or MPN-blast phase. […] The beneficial effect of phlebotomy in PV may depend not only on removing excess red blood cells (RBCs) to reduce the risk of thrombosis, but also on the resulting iron deficiency that inhibits erythropoiesis. […] However, controlling HCT has not been clearly shown to decrease symptom burden or the risk of disease progression. […] Persistent iron deficiency in PV may be a consequence of decreased iron absorption. […] Hepcidin suppression without recovery from iron deficiency raises several possibilities. […] We anticipate that the cause of iron deficiency in PV is a composite of multiple concurrent factors, most likely an aberrant iron restriction response in conjunction with altered hypoxia regulation of iron absorption. […] Understanding the dysregulation of iron metabolism in PV may enable the development of novel therapeutics.

• #53 Polycythemia Vera | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0501/p2139.html

  Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell mass. […] Secondary causes of increased red blood cell mass (e.g., heavy smoking, chronic pulmonary disease, renal disease) are more common than polycythemia vera and must be excluded. […] The median age of patients diagnosed with PV is 60 years, although it can occur in persons in all age groups. […] PV occurs with a slight predominance in men. […] The seriousness of PV is underscored by the fact that the median survival in untreated symptomatic patients after diagnosis is six to 18 months. […] Serum erythropoietin (EPO), bone marrow histopathology and karyotype, and the presence of endogenous erythroid colonies (EEC) have been proposed as diagnostic tests for PV. […] Because PV is an autonomous (i.e., EPO-independent) erythroid proliferation, serum EPO levels in PV are low or normal.

• #54 Polycythemia: Definition, causes, symptoms, and more

  https://www.medicalnewstoday.com/articles/polycythemia

  Polycythemia can have different causes, each of which has its own treatment options. […] There are two types of polycythemia, which have different causes. […] Primary polycythemia is also called polycythemia vera (PV). […] PV is a rare, slow-growing blood cancer that is a type of condition known as a myeloproliferative neoplasm. PV causes the bone marrow to create excess precursor blood cells that develop and function abnormally, leading to the production of too many red blood cells. […] Secondary polycythemia can occur if the increase in red blood cells is not due to the myeloproliferative disease of PV. […] Causes of secondary polycythemia include: being at a very high altitude, obstructive sleep apnea, certain types of tumor, heart or lung disease that causes a low oxygen level in the body.

• #55 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Secondary polycythemia is defined as an absolute increase in red blood cell mass that is caused by enhanced stimulation of red blood cell production. […] Enhanced erythroid stimulation can be a physiologic response to generalized or localized tissue hypoxia, as in the following settings: […] Because of the decreased ambient oxygen concentration at high altitudes, people living in those locales can develop compensatory erythrocytosis as a physiologic response to tissue hypoxia. […] Chronic obstructive pulmonary disease is commonly due to a large amount of ventilation in poor gas exchange units (high ventilation-to-perfusion ratios). […] Alveolar hypoventilation can result from periodic breathing and oxygen desaturation (sleep apnea) or morbid obesity (Pickwickian syndrome). […] Cardiovascular diseases associated with a right-to-left shunt (arteriovenous malformations) can result in venous blood mixing in the arterial system and delivering low oxygen levels to tissues.

• #56 Polycythemia – Wikipedia

  https://en.wikipedia.org/wiki/Polycythemia

  Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. […] Conditions where the secondary polycythemia is not caused by physiologic adaptation, and occurs irrespective of body needs include: Neoplasms Renal cell carcinoma, liver tumors, Von HippelLindau disease, and endocrine abnormalities including pheochromocytoma and adrenal adenoma with Cushing’s syndrome.

• #57 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Secondary polycythemia is defined as an absolute increase in red blood cell mass that is caused by enhanced stimulation of red blood cell production. […] Enhanced erythroid stimulation can be a physiologic response to generalized or localized tissue hypoxia, as in the following settings: […] Because of the decreased ambient oxygen concentration at high altitudes, people living in those locales can develop compensatory erythrocytosis as a physiologic response to tissue hypoxia. […] Chronic obstructive pulmonary disease is commonly due to a large amount of ventilation in poor gas exchange units (high ventilation-to-perfusion ratios). […] Alveolar hypoventilation can result from periodic breathing and oxygen desaturation (sleep apnea) or morbid obesity (Pickwickian syndrome). […] Cardiovascular diseases associated with a right-to-left shunt (arteriovenous malformations) can result in venous blood mixing in the arterial system and delivering low oxygen levels to tissues.

• #58 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Secondary polycythemia is defined as an absolute increase in red blood cell mass that is caused by enhanced stimulation of red blood cell production. […] Enhanced erythroid stimulation can be a physiologic response to generalized or localized tissue hypoxia, as in the following settings: […] Because of the decreased ambient oxygen concentration at high altitudes, people living in those locales can develop compensatory erythrocytosis as a physiologic response to tissue hypoxia. […] Chronic obstructive pulmonary disease is commonly due to a large amount of ventilation in poor gas exchange units (high ventilation-to-perfusion ratios). […] Alveolar hypoventilation can result from periodic breathing and oxygen desaturation (sleep apnea) or morbid obesity (Pickwickian syndrome). […] Cardiovascular diseases associated with a right-to-left shunt (arteriovenous malformations) can result in venous blood mixing in the arterial system and delivering low oxygen levels to tissues.

• #59 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Secondary polycythemia is defined as an absolute increase in red blood cell mass that is caused by enhanced stimulation of red blood cell production. […] Enhanced erythroid stimulation can be a physiologic response to generalized or localized tissue hypoxia, as in the following settings: […] Because of the decreased ambient oxygen concentration at high altitudes, people living in those locales can develop compensatory erythrocytosis as a physiologic response to tissue hypoxia. […] Chronic obstructive pulmonary disease is commonly due to a large amount of ventilation in poor gas exchange units (high ventilation-to-perfusion ratios). […] Alveolar hypoventilation can result from periodic breathing and oxygen desaturation (sleep apnea) or morbid obesity (Pickwickian syndrome). […] Cardiovascular diseases associated with a right-to-left shunt (arteriovenous malformations) can result in venous blood mixing in the arterial system and delivering low oxygen levels to tissues.

• #60 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Secondary polycythemia is defined as an absolute increase in red blood cell mass that is caused by enhanced stimulation of red blood cell production. […] Enhanced erythroid stimulation can be a physiologic response to generalized or localized tissue hypoxia, as in the following settings: […] Because of the decreased ambient oxygen concentration at high altitudes, people living in those locales can develop compensatory erythrocytosis as a physiologic response to tissue hypoxia. […] Chronic obstructive pulmonary disease is commonly due to a large amount of ventilation in poor gas exchange units (high ventilation-to-perfusion ratios). […] Alveolar hypoventilation can result from periodic breathing and oxygen desaturation (sleep apnea) or morbid obesity (Pickwickian syndrome). […] Cardiovascular diseases associated with a right-to-left shunt (arteriovenous malformations) can result in venous blood mixing in the arterial system and delivering low oxygen levels to tissues.

• #61 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Secondary polycythemia is defined as an absolute increase in red blood cell mass that is caused by enhanced stimulation of red blood cell production. […] Enhanced erythroid stimulation can be a physiologic response to generalized or localized tissue hypoxia, as in the following settings: […] Because of the decreased ambient oxygen concentration at high altitudes, people living in those locales can develop compensatory erythrocytosis as a physiologic response to tissue hypoxia. […] Chronic obstructive pulmonary disease is commonly due to a large amount of ventilation in poor gas exchange units (high ventilation-to-perfusion ratios). […] Alveolar hypoventilation can result from periodic breathing and oxygen desaturation (sleep apnea) or morbid obesity (Pickwickian syndrome). […] Cardiovascular diseases associated with a right-to-left shunt (arteriovenous malformations) can result in venous blood mixing in the arterial system and delivering low oxygen levels to tissues.

• #62 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Hemoglobin abnormalities associated with high oxygen affinity and congenital defects can lead to oxidized hemoglobin or methemoglobin. These conditions are usually familial. […] Exposure to carbon monoxide, such as by smoking or working in automobile tunnels, results in an acquired condition. […] Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. […] Inappropriate stimulation of EPO production may occur in the following settings: […] Benign renal lesions, such as hydronephrosis and cysts, can stimulate EPO production, possibly due to compromised renal blood flow by compressive or vasoconstrictive mechanisms. […] Malignant and benign tumors that secrete EPO have been observed in patients with renal carcinomas, cerebellar hemangioblastomas, adrenal carcinomas, adrenal adenomas, hepatomas, and uterine leiomyomas.

• #63 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Hemoglobin abnormalities associated with high oxygen affinity and congenital defects can lead to oxidized hemoglobin or methemoglobin. These conditions are usually familial. […] Exposure to carbon monoxide, such as by smoking or working in automobile tunnels, results in an acquired condition. […] Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. […] Inappropriate stimulation of EPO production may occur in the following settings: […] Benign renal lesions, such as hydronephrosis and cysts, can stimulate EPO production, possibly due to compromised renal blood flow by compressive or vasoconstrictive mechanisms. […] Malignant and benign tumors that secrete EPO have been observed in patients with renal carcinomas, cerebellar hemangioblastomas, adrenal carcinomas, adrenal adenomas, hepatomas, and uterine leiomyomas.

• #64 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Hemoglobin abnormalities associated with high oxygen affinity and congenital defects can lead to oxidized hemoglobin or methemoglobin. These conditions are usually familial. […] Exposure to carbon monoxide, such as by smoking or working in automobile tunnels, results in an acquired condition. […] Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. […] Inappropriate stimulation of EPO production may occur in the following settings: […] Benign renal lesions, such as hydronephrosis and cysts, can stimulate EPO production, possibly due to compromised renal blood flow by compressive or vasoconstrictive mechanisms. […] Malignant and benign tumors that secrete EPO have been observed in patients with renal carcinomas, cerebellar hemangioblastomas, adrenal carcinomas, adrenal adenomas, hepatomas, and uterine leiomyomas.

• #65 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Hemoglobin abnormalities associated with high oxygen affinity and congenital defects can lead to oxidized hemoglobin or methemoglobin. These conditions are usually familial. […] Exposure to carbon monoxide, such as by smoking or working in automobile tunnels, results in an acquired condition. […] Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. […] Inappropriate stimulation of EPO production may occur in the following settings: […] Benign renal lesions, such as hydronephrosis and cysts, can stimulate EPO production, possibly due to compromised renal blood flow by compressive or vasoconstrictive mechanisms. […] Malignant and benign tumors that secrete EPO have been observed in patients with renal carcinomas, cerebellar hemangioblastomas, adrenal carcinomas, adrenal adenomas, hepatomas, and uterine leiomyomas.

• #66 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Hemoglobin abnormalities associated with high oxygen affinity and congenital defects can lead to oxidized hemoglobin or methemoglobin. These conditions are usually familial. […] Exposure to carbon monoxide, such as by smoking or working in automobile tunnels, results in an acquired condition. […] Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. […] Inappropriate stimulation of EPO production may occur in the following settings: […] Benign renal lesions, such as hydronephrosis and cysts, can stimulate EPO production, possibly due to compromised renal blood flow by compressive or vasoconstrictive mechanisms. […] Malignant and benign tumors that secrete EPO have been observed in patients with renal carcinomas, cerebellar hemangioblastomas, adrenal carcinomas, adrenal adenomas, hepatomas, and uterine leiomyomas.

• #67 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Hemoglobin abnormalities associated with high oxygen affinity and congenital defects can lead to oxidized hemoglobin or methemoglobin. These conditions are usually familial. […] Exposure to carbon monoxide, such as by smoking or working in automobile tunnels, results in an acquired condition. […] Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. […] Inappropriate stimulation of EPO production may occur in the following settings: […] Benign renal lesions, such as hydronephrosis and cysts, can stimulate EPO production, possibly due to compromised renal blood flow by compressive or vasoconstrictive mechanisms. […] Malignant and benign tumors that secrete EPO have been observed in patients with renal carcinomas, cerebellar hemangioblastomas, adrenal carcinomas, adrenal adenomas, hepatomas, and uterine leiomyomas.

• #68 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Hemoglobin abnormalities associated with high oxygen affinity and congenital defects can lead to oxidized hemoglobin or methemoglobin. These conditions are usually familial. […] Exposure to carbon monoxide, such as by smoking or working in automobile tunnels, results in an acquired condition. […] Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. […] Inappropriate stimulation of EPO production may occur in the following settings: […] Benign renal lesions, such as hydronephrosis and cysts, can stimulate EPO production, possibly due to compromised renal blood flow by compressive or vasoconstrictive mechanisms. […] Malignant and benign tumors that secrete EPO have been observed in patients with renal carcinomas, cerebellar hemangioblastomas, adrenal carcinomas, adrenal adenomas, hepatomas, and uterine leiomyomas.

• #69 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Hemoglobin abnormalities associated with high oxygen affinity and congenital defects can lead to oxidized hemoglobin or methemoglobin. These conditions are usually familial. […] Exposure to carbon monoxide, such as by smoking or working in automobile tunnels, results in an acquired condition. […] Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. […] Inappropriate stimulation of EPO production may occur in the following settings: […] Benign renal lesions, such as hydronephrosis and cysts, can stimulate EPO production, possibly due to compromised renal blood flow by compressive or vasoconstrictive mechanisms. […] Malignant and benign tumors that secrete EPO have been observed in patients with renal carcinomas, cerebellar hemangioblastomas, adrenal carcinomas, adrenal adenomas, hepatomas, and uterine leiomyomas.

• #70 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Hemoglobin abnormalities associated with high oxygen affinity and congenital defects can lead to oxidized hemoglobin or methemoglobin. These conditions are usually familial. […] Exposure to carbon monoxide, such as by smoking or working in automobile tunnels, results in an acquired condition. […] Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. […] Inappropriate stimulation of EPO production may occur in the following settings: […] Benign renal lesions, such as hydronephrosis and cysts, can stimulate EPO production, possibly due to compromised renal blood flow by compressive or vasoconstrictive mechanisms. […] Malignant and benign tumors that secrete EPO have been observed in patients with renal carcinomas, cerebellar hemangioblastomas, adrenal carcinomas, adrenal adenomas, hepatomas, and uterine leiomyomas.

• #71 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Blood doping is an illegal practice. […] Illicit use of androgenic steroids to build muscles and strength can also increase red blood cell mass by stimulating endogenous serum EPO levels. […] Hemoglobin mutants associated with tight binding to oxygen and a failure to deliver oxygen in the venous blood can cause high EPO levels. […] A von Hippel-Lindau gene mutation results in polycythemia by altering the von Hippel-Lindau protein, which plays an important role in sensing hypoxia and binds to hydroxylated HIF1-alpha to serve as a recognition site of an E3-ubiquitin ligase complex. […] Chuvash polycythemia is caused by an autosomal recessive gene mutation on the von Hippel-Lindau gene, which results in the upregulation of the HIF1-alpha target gene and causes elevations in EPO levels.

• #72 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/

  Chuvash polycythemia is caused by a germline mutation in the VHL gene that is inherited in an autosomal-recessive manner from both parents. This disorder of hypoxia sensing, the first to be described, results from a loss-of-function mutation in a negative regulator of HIFs, the VHL gene. […] 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 (protein S, tissue factor, thrombospondin 1, and likely others).

• #73 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  The administration of androgen esters to hypogonadal men can lead to polycythemia. […] The incidence of testosterone-associated polycythemia may be lower in men receiving pharmacokinetically steady-state delivery of testosterone formulations, as occurs following the subcutaneous implantation of testosterone pellets, than it is in men receiving intramuscular injections of shorter-acting androgen esters. […] Secondary polycythemia has been reported as a paraneoplastic phenomenon in patients with testicular cancer.

• #74 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Blood doping is an illegal practice. […] Illicit use of androgenic steroids to build muscles and strength can also increase red blood cell mass by stimulating endogenous serum EPO levels. […] Hemoglobin mutants associated with tight binding to oxygen and a failure to deliver oxygen in the venous blood can cause high EPO levels. […] A von Hippel-Lindau gene mutation results in polycythemia by altering the von Hippel-Lindau protein, which plays an important role in sensing hypoxia and binds to hydroxylated HIF1-alpha to serve as a recognition site of an E3-ubiquitin ligase complex. […] Chuvash polycythemia is caused by an autosomal recessive gene mutation on the von Hippel-Lindau gene, which results in the upregulation of the HIF1-alpha target gene and causes elevations in EPO levels.

• #75 Secondary Polycythemia: Practice Essentials, Pathophysiology, Etiology

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

  Secondary polycythemia is defined as an absolute increase in red blood cell mass that is caused by enhanced stimulation of red blood cell production. […] Enhanced erythroid stimulation can be a physiologic response to generalized or localized tissue hypoxia, as in the following settings: […] Because of the decreased ambient oxygen concentration at high altitudes, people living in those locales can develop compensatory erythrocytosis as a physiologic response to tissue hypoxia. […] Chronic obstructive pulmonary disease is commonly due to a large amount of ventilation in poor gas exchange units (high ventilation-to-perfusion ratios). […] Alveolar hypoventilation can result from periodic breathing and oxygen desaturation (sleep apnea) or morbid obesity (Pickwickian syndrome). […] Cardiovascular diseases associated with a right-to-left shunt (arteriovenous malformations) can result in venous blood mixing in the arterial system and delivering low oxygen levels to tissues.

• #76 Polycythemia – Wikipedia

  https://en.wikipedia.org/wiki/Polycythemia

  Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. […] Conditions where the secondary polycythemia is not caused by physiologic adaptation, and occurs irrespective of body needs include: Neoplasms Renal cell carcinoma, liver tumors, Von HippelLindau disease, and endocrine abnormalities including pheochromocytoma and adrenal adenoma with Cushing’s syndrome.

• #77 Polycythaemia Vera: Causes, Symptoms, and Treatment

  https://patient.info/doctor/polycythaemia-vera-pro

  Polycythaemia vera (PV) is a clonal disorder of haematopoietic stem/progenitor cells. It is characterised by a V617F point mutation in JAK2 exon 14 or less common mutations in exon 12. […] The discovery of mutations in JAK2 as the underlying molecular basis of PV has led to the development of several targeted therapies, including JAK inhibitors. […] JAK2-positive PV is diagnosed if the JAK2 mutation is identified. […] JAK2-negative PV is diagnosed if the JAK2 mutation is not identified. […] It is important to distinguish three causes of raised haemoglobin level: relative polycythaemia, essential polycythaemia, and secondary polycythaemia. […] Secondary polycythaemia is due to hypoxia causing erythropoietin release as in Eisenmenger’s syndrome, chronic obstructive pulmonary disease (COPD) or smoking. […] Other tumours have been reported to produce erythropoietin or a similar substance.

• #78 Polycythaemia Vera: Causes, Symptoms, and Treatment

  https://patient.info/doctor/polycythaemia-vera-pro

  Polycythaemia vera (PV) is a clonal disorder of haematopoietic stem/progenitor cells. It is characterised by a V617F point mutation in JAK2 exon 14 or less common mutations in exon 12. […] The discovery of mutations in JAK2 as the underlying molecular basis of PV has led to the development of several targeted therapies, including JAK inhibitors. […] JAK2-positive PV is diagnosed if the JAK2 mutation is identified. […] JAK2-negative PV is diagnosed if the JAK2 mutation is not identified. […] It is important to distinguish three causes of raised haemoglobin level: relative polycythaemia, essential polycythaemia, and secondary polycythaemia. […] Secondary polycythaemia is due to hypoxia causing erythropoietin release as in Eisenmenger’s syndrome, chronic obstructive pulmonary disease (COPD) or smoking. […] Other tumours have been reported to produce erythropoietin or a similar substance.

• #79 Dysregulated iron metabolism in polycythemia vera: etiology and consequences | Leukemia

  https://www.nature.com/articles/s41375-018-0207-9

  The primary goals of treating PV patients are to ameliorate symptoms, reduce the risk of thrombosis, and prevent transformation to MF and/or MPN-blast phase. […] The beneficial effect of phlebotomy in PV may depend not only on removing excess red blood cells (RBCs) to reduce the risk of thrombosis, but also on the resulting iron deficiency that inhibits erythropoiesis. […] However, controlling HCT has not been clearly shown to decrease symptom burden or the risk of disease progression. […] Persistent iron deficiency in PV may be a consequence of decreased iron absorption. […] Hepcidin suppression without recovery from iron deficiency raises several possibilities. […] We anticipate that the cause of iron deficiency in PV is a composite of multiple concurrent factors, most likely an aberrant iron restriction response in conjunction with altered hypoxia regulation of iron absorption. […] Understanding the dysregulation of iron metabolism in PV may enable the development of novel therapeutics.

• #80 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. […] Nonmodifiable risk factors for PV include older age, male sex, White race, and European descent. […] Modifiable risk factors for PV include smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia. […] Smoking cessation decreases the risk of thrombosis. […] Currently, no medications have been shown to cure the disease or to reduce the risk of conversion to leukemia and myelofibrosis. […] Poor prognostic features include age older than 60 years, history of thrombosis, leukocytosis, high JAK2 burden, abnormal karyotype, and established cardiovascular risk factors such as smoking, hypertension, diabetes, obesity, and hyperlipidemia. […] Without treatment, death typically occurs within two years, mostly from thrombotic events. […] The risk of blast transformation to acute myeloid leukemia or myelodysplastic syndrome over 15 years is 5.5% to 18.7%. […] Progression to myelofibrosis over 15 years is 6% to 14%.

• #81 Polycythemia Vera-Associated Complications: Pathogenesis, Clinical Man | JBM

  https://www.dovepress.com/polycythemia-vera-associated-complications-pathogenesis-clinical-manif-peer-reviewed-fulltext-article-JBM

  Advanced age, typically defined as 60 years old, is a well-established risk factor for disease progression and adverse outcomes among PV patients. […] Leukocytosis is associated with multiple disease complications among MPNs, including increased risk of arterial and venous thrombosis, myocardial infarction, MF transformation and evolution to leukemia. […] The JAK/STAT pathway plays an integral role in normal hematopoiesis. However, a gain-of-function mutation in JAK2 leads to constitutively activated JAK/STAT signaling, thereby giving rise to myeloid neoplasms. […] There is increasing awareness that additional non-driver somatic mutations may add to prognostication in PV. […] Several risk factors are common for both myelofibrotic and leukemic progression, including age, leukocytosis, and novel non-driver mutations.

• #82 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. […] Nonmodifiable risk factors for PV include older age, male sex, White race, and European descent. […] Modifiable risk factors for PV include smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia. […] Smoking cessation decreases the risk of thrombosis. […] Currently, no medications have been shown to cure the disease or to reduce the risk of conversion to leukemia and myelofibrosis. […] Poor prognostic features include age older than 60 years, history of thrombosis, leukocytosis, high JAK2 burden, abnormal karyotype, and established cardiovascular risk factors such as smoking, hypertension, diabetes, obesity, and hyperlipidemia. […] Without treatment, death typically occurs within two years, mostly from thrombotic events. […] The risk of blast transformation to acute myeloid leukemia or myelodysplastic syndrome over 15 years is 5.5% to 18.7%. […] Progression to myelofibrosis over 15 years is 6% to 14%.

• #83 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. […] Nonmodifiable risk factors for PV include older age, male sex, White race, and European descent. […] Modifiable risk factors for PV include smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia. […] Smoking cessation decreases the risk of thrombosis. […] Currently, no medications have been shown to cure the disease or to reduce the risk of conversion to leukemia and myelofibrosis. […] Poor prognostic features include age older than 60 years, history of thrombosis, leukocytosis, high JAK2 burden, abnormal karyotype, and established cardiovascular risk factors such as smoking, hypertension, diabetes, obesity, and hyperlipidemia. […] Without treatment, death typically occurs within two years, mostly from thrombotic events. […] The risk of blast transformation to acute myeloid leukemia or myelodysplastic syndrome over 15 years is 5.5% to 18.7%. […] Progression to myelofibrosis over 15 years is 6% to 14%.

• #84 Polycythemia Vera | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions/p/polycythemia-vera.html

  Polycythemia vera is caused by a genetic change (mutation) that develops during your lifetime. It’s not an inherited genetic disorder. In most cases, it’s not known why this happens. […] Polycythemia vera can be fatal if not diagnosed and treated. It can cause blood clots resulting in a heart attack, stroke, or pulmonary embolism. […] Polycythemia vera is a rare blood disorder in which there is an increase in all blood cells, particularly red blood cells. […] The increase in blood cells makes the blood thicker. […] Thick blood can lead blood clots forming in blood vessels. This can cause strokes or tissue and organ damage.

• #85 Polycythemia Vera in Pregnancy: A Descriptive Review of the Literature

  https://www.imrpress.com/journal/CEOG/50/4/10.31083/j.ceog5004077/htm

  In contrast to primary polycythemia, secondary absolute polycythemia refers to an increase in RBC mass due to elevated serum EPO from another underlying condition, which can be associated with high altitude, hypoxia/cardiopulmonary, and renal and autonomous EPO-producing neoplastic processes. […] The diagnosis of PV is relatively rare in younger women since only 15% of PV patients are less than 40 years of age at the time of diagnosis. […] Pregnancy itself does not appear to alter the long term prognosis of MPNs like PV. […] Hypothetically the known physiologic relative reduction in red cell mass due to intravascular volume expansion in pregnancy may actually benefit the patient with PV. […] The study found that these patients have an increased rate of fetal loss, especially related to the presence of specific JAK2 mutations, in particular JAK2V617F.

• #86 Polycythemia Vera in Pregnancy: A Descriptive Review of the Literature

  https://www.imrpress.com/journal/CEOG/50/4/10.31083/j.ceog5004077/htm

  Pregnant patients with PV appear to be at higher risk for a variety of other pregnancy-related complications, including gestational hypertension, preeclampsia, uteroplacental insufficiency, placental abruption, fetal growth restriction, premature birth, and intrauterine fetal demise. […] Despite the paucity of data, the increased risk for these adverse outcomes appears to be attenuated by the use of sequential phlebotomy and anti-thrombotic therapy in some patients. […] Many of these recommendations have been extrapolated from data on other MPNs or have been empirically derived based on expert opinion. […] Due to the concern for thrombosis in patients with PV, the main interventional strategies focus on prevention of thrombotic complications. […] Their guidelines direct that in otherwise low-risk pregnancies, it is recommended to keep the hematocrit within a gestational-appropriate range via serial phlebotomies, and to use low-dose aspirin throughout pregnancy and the postpartum period.

• #87 Polycythemia Vera in Pregnancy: A Descriptive Review of the Literature

  https://www.imrpress.com/journal/CEOG/50/4/10.31083/j.ceog5004077/htm

  Pregnant patients with PV appear to be at higher risk for a variety of other pregnancy-related complications, including gestational hypertension, preeclampsia, uteroplacental insufficiency, placental abruption, fetal growth restriction, premature birth, and intrauterine fetal demise. […] Despite the paucity of data, the increased risk for these adverse outcomes appears to be attenuated by the use of sequential phlebotomy and anti-thrombotic therapy in some patients. […] Many of these recommendations have been extrapolated from data on other MPNs or have been empirically derived based on expert opinion. […] Due to the concern for thrombosis in patients with PV, the main interventional strategies focus on prevention of thrombotic complications. […] Their guidelines direct that in otherwise low-risk pregnancies, it is recommended to keep the hematocrit within a gestational-appropriate range via serial phlebotomies, and to use low-dose aspirin throughout pregnancy and the postpartum period.

• #88 Polycythemia Vera | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0501/p2139.html

  The nonalkylating myelosuppressive agent hydroxyurea is widely used in the treatment of PV, because it is less leukemogenic. […] Recombinant interferon alfa-2b reduces myeloproliferation and splenomegaly, and alleviates the symptom of pruritus. […] A risk-stratified approach to the management of PV is currently recommended.

• #89 Dysregulated iron metabolism in polycythemia vera: etiology and consequences | Leukemia

  https://www.nature.com/articles/s41375-018-0207-9

  The primary goals of treating PV patients are to ameliorate symptoms, reduce the risk of thrombosis, and prevent transformation to MF and/or MPN-blast phase. […] The beneficial effect of phlebotomy in PV may depend not only on removing excess red blood cells (RBCs) to reduce the risk of thrombosis, but also on the resulting iron deficiency that inhibits erythropoiesis. […] However, controlling HCT has not been clearly shown to decrease symptom burden or the risk of disease progression. […] Persistent iron deficiency in PV may be a consequence of decreased iron absorption. […] Hepcidin suppression without recovery from iron deficiency raises several possibilities. […] We anticipate that the cause of iron deficiency in PV is a composite of multiple concurrent factors, most likely an aberrant iron restriction response in conjunction with altered hypoxia regulation of iron absorption. […] Understanding the dysregulation of iron metabolism in PV may enable the development of novel therapeutics.

• #90 Polycythemia Vera – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK557660/

  Polycythemia vera is a myeloproliferative disorder associated with a Janus kinase-2 (JAK2) mutation that causes the neoplastic proliferation of the hematopoietic progenitor cells. […] The etiology of the disease process appears to be neoplastic proliferation. There is a signaling defect leading to an abnormal response to growth factors, and the abnormal clonal line interferes with normal lineage proliferation. The Janus kinase-2 (JAK2) gene involved with intracellular signaling is mutated in 90% of cases of polycythemia vera (PV). […] Cytogenetic studies show the presence of an abnormal karyotype in the hematopoietic progenitor cells in approximately 34% of patients with PV. At the time of diagnosis, 20% of patients have cytogenetic abnormalities, increasing to more than 80% for those with more than 10 years of follow-up care.

• #91 Polycythemia Vera – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/polycythemia-vera

  Polycythemia vera is due to mutations in the Janus kinase 2 (JAK2) gene, which produces a protein (enzyme) that stimulates excessive production of blood cells. […] More than 95% of people with polycythemia vera have a mutation in the JAK2 gene. This mutation causes excess blood cell production. […] In addition, mutations in the calreticulin gene (CALR) and other genes have been found in some people with polycythemia vera. These mutations lead to sustained activation of JAK2 kinase, the enzyme that causes excess red blood cell production.

• #92 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. […] Nonmodifiable risk factors for PV include older age, male sex, White race, and European descent. […] Modifiable risk factors for PV include smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia. […] Smoking cessation decreases the risk of thrombosis. […] Currently, no medications have been shown to cure the disease or to reduce the risk of conversion to leukemia and myelofibrosis. […] Poor prognostic features include age older than 60 years, history of thrombosis, leukocytosis, high JAK2 burden, abnormal karyotype, and established cardiovascular risk factors such as smoking, hypertension, diabetes, obesity, and hyperlipidemia. […] Without treatment, death typically occurs within two years, mostly from thrombotic events. […] The risk of blast transformation to acute myeloid leukemia or myelodysplastic syndrome over 15 years is 5.5% to 18.7%. […] Progression to myelofibrosis over 15 years is 6% to 14%.

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

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

  Polycythemia vera occurs in your bone marrow, the soft, spongy material at the center of your bones. This is where new blood cells grow. PV begins when a single gene within a single stem cell in the bone marrow malfunctions. More than 90% of the time, its a gene called JAK2. The mutated gene gives instructions to the stem cell to continually reproduce itself. All of the reproduced cells also continue to reproduce, until the abnormal cells crowd out the normal cells in your bone marrow. Most of the time, the JAK2 gene mutation is acquired, which means it isnt inherited from a family member. It occurs for unknown reasons sometime during your life. But there have been a few documented cases of multiple family members developing polycythemia vera. […] A gene mutation that occurs for unknown reasons, usually sometime during the course of your life, causes polycythemia vera.

• #94 Polycythemia Vera | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0501/p2139.html

  Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell mass. […] Secondary causes of increased red blood cell mass (e.g., heavy smoking, chronic pulmonary disease, renal disease) are more common than polycythemia vera and must be excluded. […] The median age of patients diagnosed with PV is 60 years, although it can occur in persons in all age groups. […] PV occurs with a slight predominance in men. […] The seriousness of PV is underscored by the fact that the median survival in untreated symptomatic patients after diagnosis is six to 18 months. […] Serum erythropoietin (EPO), bone marrow histopathology and karyotype, and the presence of endogenous erythroid colonies (EEC) have been proposed as diagnostic tests for PV. […] Because PV is an autonomous (i.e., EPO-independent) erythroid proliferation, serum EPO levels in PV are low or normal.

• #95 Polycythemia: Definition, causes, symptoms, and more

  https://www.medicalnewstoday.com/articles/polycythemia

  Polycythemia can have different causes, each of which has its own treatment options. […] There are two types of polycythemia, which have different causes. […] Primary polycythemia is also called polycythemia vera (PV). […] PV is a rare, slow-growing blood cancer that is a type of condition known as a myeloproliferative neoplasm. PV causes the bone marrow to create excess precursor blood cells that develop and function abnormally, leading to the production of too many red blood cells. […] Secondary polycythemia can occur if the increase in red blood cells is not due to the myeloproliferative disease of PV. […] Causes of secondary polycythemia include: being at a very high altitude, obstructive sleep apnea, certain types of tumor, heart or lung disease that causes a low oxygen level in the body.

• #96 Polycythaemia Vera: Causes, Symptoms, and Treatment

  https://patient.info/doctor/polycythaemia-vera-pro

  Polycythaemia vera (PV) is a clonal disorder of haematopoietic stem/progenitor cells. It is characterised by a V617F point mutation in JAK2 exon 14 or less common mutations in exon 12. […] The discovery of mutations in JAK2 as the underlying molecular basis of PV has led to the development of several targeted therapies, including JAK inhibitors. […] JAK2-positive PV is diagnosed if the JAK2 mutation is identified. […] JAK2-negative PV is diagnosed if the JAK2 mutation is not identified. […] It is important to distinguish three causes of raised haemoglobin level: relative polycythaemia, essential polycythaemia, and secondary polycythaemia. […] Secondary polycythaemia is due to hypoxia causing erythropoietin release as in Eisenmenger’s syndrome, chronic obstructive pulmonary disease (COPD) or smoking. […] Other tumours have been reported to produce erythropoietin or a similar substance.

• #97 Polycythemia Vera | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions/p/polycythemia-vera.html

  Polycythemia vera is caused by a genetic change (mutation) that develops during your lifetime. It’s not an inherited genetic disorder. In most cases, it’s not known why this happens. […] Polycythemia vera can be fatal if not diagnosed and treated. It can cause blood clots resulting in a heart attack, stroke, or pulmonary embolism. […] Polycythemia vera is a rare blood disorder in which there is an increase in all blood cells, particularly red blood cells. […] The increase in blood cells makes the blood thicker. […] Thick blood can lead blood clots forming in blood vessels. This can cause strokes or tissue and organ damage.

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