polycythemia vera

People with PV can be asymptomatic.[Polycythemia vera EBSCO database] verified by URAC; accessed from Mount Sinai Hospital, New York Symptoms of PVhttps://www.lls.org/myeloproliferative-neoplasms/polycythemia-vera/signs-and-symptoms{{Cite web|url=https://www.cancerresearchuk.org/about-cancer/polycythaemia-vera/what-is-pv|title=What is polycythaemia vera (PV)?|website=www.cancerresearchuk.org}} that may aid identification include;

• pruritus (itching), particularly after exposure to warm water (such as when taking a bath),{{cite journal |vauthors=Saini KS, Patnaik MM, Tefferi A | title = Polycythemia vera-associated pruritus and its management | journal = Eur J Clin Invest | volume = 40 | issue = 9 | pages = 828–34 | year = 2010 | pmid = 20597963 | doi = 10.1111/j.1365-2362.2010.02334.x| s2cid = 13638890 }} which may be due to abnormal histamine release{{cite journal |vauthors=Steinman H, Kobza-Black A, Lotti T, Brunetti L, Panconesi E, Greaves M | title = Polycythaemia rubra vera and water-induced pruritus: blood histamine levels and cutaneous fibrinolytic activity before and after water challenge | journal = Br J Dermatol | volume = 116 | issue = 3 | pages = 329–33 | year = 1987 | pmid = 3567071 | doi = 10.1111/j.1365-2133.1987.tb05846.x| s2cid = 22068469 }}{{cite journal |vauthors=Jackson N, Burt D, Crocker J, Boughton B | title = Skin mast cells in polycythaemia vera: relationship to the pathogenesis and treatment of pruritus | journal = Br J Dermatol | volume = 116 | issue = 1 | pages = 21–9 | year = 1987 | pmid = 3814512 | doi = 10.1111/j.1365-2133.1987.tb05787.x| s2cid = 38261640 }} or prostaglandin production.{{cite journal |vauthors=Fjellner B, Hägermark O | title = Pruritus in polycythemia vera: treatment with aspirin and possibility of platelet involvement | journal = Acta Derm Venereol | volume = 59 | issue = 6 | pages = 505–12 | year = 1979 | doi = 10.2340/0001555559505512 | pmid = 94209 | s2cid=6909368 | doi-access = free }} Such itching is present in 40%-55% of patients with PV.{{cite journal|vauthors=Jones AV, Chase A, Silver RT, Oscier D, Zoi K, Wang YL, Cario H, Pahl HL, Collins A, Reiter A, Grand F, Cross NC|title=JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms|journal=Nature Genetics|volume=41|issue=4|pages=446-449|doi=10.1038/ng.334|pmid=19287382|pmc=4120192|year=2009}}
• erythromelalgia,{{cite journal |vauthors=van Genderen P, Michiels J | title = Erythromelalgia: a pathognomonic microvascular thrombotic complication in essential thrombocythemia and polycythemia vera | journal = Semin Thromb Hemost | volume = 23 | issue = 4 | pages = 357–63 | year = 1997 | pmid = 9263352 | doi = 10.1055/s-2007-996109}} a burning pain in the hands or feet, usually accompanied by a reddish or bluish coloration of the skin. Erythromelalgia is caused by an increased platelet count or increased platelet "stickiness" (aggregation), resulting in the formation of tiny blood clots in the vessels of the extremity; it responds rapidly to treatment with aspirin.{{cite journal | author = Michiels J | title = Erythromelalgia and vascular complications in polycythemia vera | journal = Semin Thromb Hemost | volume = 23 | issue = 5 | pages = 441–54 | year = 1997 | pmid = 9387203 | doi = 10.1055/s-2007-996121}}{{cite journal |vauthors=Landolfi R, Ciabattoni G, Patrignani P, Castellana M, Pogliani E, Bizzi B, Patrono C | title = Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo | journal = Blood | volume = 80 | issue = 8 | pages = 1965–71 | year = 1992 | pmid = 1327286| doi = 10.1182/blood.V80.8.1965.1965 | doi-access = free }}

There are many other possible symptoms of PV, including night sweats and fatigue. No symptoms are required for diagnosis.

Other diseases that may be present with PV include;

• Splenomegaly may cause the spleen to be palpable in some patients, which may be associated with both the V617F mutation and the development of myelofibrosis.{{cite journal|vauthors=Lee MW, Yeon SH, Ryu H, Song IC, Lee HJ, Yun HJ, Kim SY, Lee JE, Shin KS, Jo DY|title=Volumetric Splenomegaly in Patients With Polycythemia Vera|journal=Journal of Korean Medical Science|volume=37|issue=11|id=Art. No. e87|doi=10.3346/jkms.2022.37.e87|doi-access=free|pmid=35315598|pmc=8938613|year=2022}}
• Gouty arthritis may be present in up to 20% of patients.
• Peptic ulcer disease is common in patients with PV; most likely due to increased histamine from mast cells, but may be related to an increased susceptibility to infection with the ulcer-causing bacterium H. pylori.{{cite journal |vauthors=Torgano G, Mandelli C, Massaro P, Abbiati C, Ponzetto A, Bertinieri G, Bogetto S, Terruzzi E, de Franchis R | title = Gastroduodenal lesions in polycythaemia vera: frequency and role of Helicobacter pylori | journal = Br J Haematol | volume = 117 | issue = 1 | pages = 198–202 | year = 2002 | pmid = 11918555 | doi = 10.1046/j.1365-2141.2002.03380.x| doi-access = free }}

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.{{cite book|veditors=Kumar, V, Abbas AK, Fausto N, Mitchell RN|title=Robbins Basic Pathology|edition=8th|publisher=Saunders Elsevier|year=2007|isbn=978-1-4160-2973-1}}{{page number needed|date=January 2024}}

Diagnostic criteria for polycythemia vera were modified by the World Health Organization in 2016.{{cite journal |author=Daniel A. Arber |author2=Attilio Orazi |author3=Robert Hasserjian |author4=Jürgen Thiele |author5=Michael J. Borowitz |author6=Michelle M. Le Beau |author7=Clara D. Bloomfield |author8=Mario Cazzola |author9=James W. Vardiman |title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia |journal=Blood |volume=127 |issue=20 |pages=2391–2405 |date=2016 |pmid=27069254 |doi=10.1182/blood-2016-03-643544 |s2cid=18338178 |doi-access=free }} The WHO criteria for polycythemia vera are specifically outlined in Table 4.

There are 3 major criteria for PV diagnosis:

1. A very high red blood cell count, which is usually identified by elevated levels of hemoglobin or hematocrit;
2. A bone marrow biopsy that shows hypercellularity and abnormalities in megakaryocytes; and
3. The presence of a mutation in the Janus kinase 2 (JAK2) gene.

A minor diagnostic feature is that patients usually have a very low level of erythropoietin, a growth factor that increases the production of red blood cells.{{Cite web|url=https://www.lls.org/myeloproliferative-neoplasms/polycythemia-vera/diagnosis|title=Hematocrit Levels | HCT Blood Test For Blood Cancer | LLS|website=www.lls.org}}{{cite journal|author=Verstovsek, S. |title=Highlights in polycythemia vera from the 2016 EHA congress | journal=Clin Adv Hematol Oncol |year=2016|volume=14|issue=10|pages=810–813 | pmid=27930632|url=https://www.hematologyandoncology.net/archives/october-2016/highlights-in-polycythemia-vera-from-the-2016-eha-congres/}}

As of 2025, reviews state diagnosis can be based on

• the presence of a JAK2 mutation and
• hemoglobin/hematocrit levels of >16.5 g/dL/49% in men or 16 g/dL/48% in women.

Bone marrow morphologic confirmation is advised but not mandated.{{Cite journal|url=https://pubmed.ncbi.nlm.nih.gov/37357958|title=Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management|first1=Ayalew|last1=Tefferi|first2=Tiziano|last2=Barbui|date=September 5, 2023|journal=American Journal of Hematology|volume=98|issue=9|pages=1465–1487|via=PubMed|doi=10.1002/ajh.27002|pmid=37357958}}{{Cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK557660/|title=StatPearls|first1=Xiao|last1=Lu|first2=Richard|last2=Chang|date=June 5, 2025|publisher=StatPearls Publishing|via=PubMed|pmid=32491592}}

A mutation in the JAK2 kinase (V617F) is strongly associated with polycythemia vera.{{cite journal |vauthors=Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR | s2cid=24419497 | title=Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders | journal=Lancet | year=2005 | pages=1054–61 | volume=365 | issue=9464 | pmid=15781101 | doi=10.1016/S0140-6736(05)71142-9}}{{cite journal |vauthors=Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Frohling S, Dohner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG | title=Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis | journal=Cancer Cell | year=2005 | pages=387–97 | volume=7 | issue=4 | pmid=15837627 | doi=10.1016/j.ccr.2005.03.023| doi-access=free }} 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.{{cite journal|vauthors=Zhao R, Xing S, Li Z, Fu X, Li Q, Krantz SB, Zhao ZJ|title=Identification of an Acquired JAK2 Mutation in Polycythemia Vera|journal=Journal of Biological Chemistry|year=2005|volume=280|issue=24|pages=22788-22792|doi=10.1074/jbc.C500138200|doi-access=free|pmid=15863514|pmc=1201515}} 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.{{cite journal|vauthors=Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC|title=A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders|year=2005|volume=352|issue=17|pages=1779-1790|doi=10.1056/NEJMoa051113|doi-access=free|pmid=15858187|journal=The New England Journal of Medicine}} While the JAK2 V617F mutation is generally sporadic (random), a certain inherited haplotype of JAK2 has been associated with its development.{{cite journal|vauthors=Hirvonen EA, Pitkänen E, Hemminki K, Aaltonen LA, Kilpivaara O|journal=Human Genomics|title=Whole-exome sequencing identifies novel candidate predisposition genes for familial polycythemia vera|volume=11|issue=1|id=Art. No. 6|doi=10.1186/s40246-017-0102-x|doi-access=free|pmid=28427458|pmc=5397753|year=2017}}

PV may remain stable for many years, with no effect on life expectancy, particularly if managed effectively.https://www.lls.org/myeloproliferative-neoplasms/polycythemia-vera/treatment/treatment-outcomes Studies show the median survival rate of controlled PV ranges from 10 to 20 years but most observations are of people diagnosed in their 60s. Patients live close to a normal life expectancy, but overall survival in PV is below that of age- and sex-matched general population.{{Cite journal|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.27002|title=Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management|first1=Ayalew|last1=Tefferi|first2=Tiziano|last2=Barbui|date=Jun 5, 2023|journal=American Journal of Hematology|volume=98|issue=9|pages=1465–1487|via=Wiley Online Library|doi=10.1002/ajh.27002}} Factors predicting this may include age and detailed genetic differences.

PV may cause blood clotting complications (thrombosis),https://www.lls.org/myeloproliferative-neoplasms/polycythemia-vera/disease-complications with the two main risk factors being a previous clot or clots, and age (60 years or older).https://www.lls.org/myeloproliferative-neoplasms/polycythemia-vera/treatment If PV is untreated, there is a substantial risk of Budd-Chiari syndrome (a particular hepatic vein thrombosis).{{cite journal |vauthors=Thurmes PJ, Steensma DP |title=Elevated serum erythropoietin levels in patients with Budd-Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis |journal=Eur. J. Haematol. |volume=77 |issue=1 |pages=57–60 |date=July 2006 |pmid=16827884 |doi=10.1111/j.1600-0609.2006.00667.x |s2cid=37383942 }}

PV may develop into myelofibrosis (a rare bone marrow cancer) or acute myeloid leukemia.{{Cite web|url=https://www.cancerresearchuk.org/about-cancer/polycythaemia-vera/research-coping|title=Research and coping with polycythaemia vera (PV)|website=www.cancerresearchuk.org}}

Bleeding is a possible PV complication, although major bleeds are rare.

As of 2024, despite the phenotype association with a JAK2 mutation, curative drug therapy in PV remains elusive.

The treatment goal is to prevent thrombosis. Periodic phlebotomy, to keep hematocrit level below 45%, and daily (or twice daily) aspirin (81 mg) has been called the "backbone" of treatment, regardless of risk category, if there are no contraindications.

Additional management will depend on triage into high and low risk categories.

A secondary treatment goal is to alleviate symptoms, for instance of pruritus (itching).

Frequent blood withdrawals (phlebotomy) are one form of treatment, which often may be combined with other therapies. The removal of blood from the body induces iron deficiency, thereby decreasing the hemoglobin / hematocrit level, and reducing the risk of blood clots. Phlebotomy is typically performed to bring their hematocrit (red blood cell percentage) down below 45 for men or 42 for women.{{cite journal |vauthors=Streiff MB, Smith B, Spivak JL |title=The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns |journal=Blood |volume=99 |issue=4 |pages=1144–9 |year=2002 |pmid=11830459 |doi=10.1182/blood.V99.4.1144|doi-access=free }} It has been observed that phlebotomy also reduces cognitive impairment.{{cite journal | pmid = 10894997 | volume=44 | issue=1 | title=Cognitive impairment in polycythemia vera: partial reversibility upon lowering of the hematocrit | year=2000 |vauthors=Di Pollina L, Mulligan R, Juillerat Van der Linden A, Michel JP, Gold G | s2cid=40928145 | journal=Eur. Neurol. | pages=57–9 | doi=10.1159/000008194}}

Aspirin may be taken, to reduce thrombosis risk, regardless of risk category.

Medications are also used which reduce the number of red blood cells. These include hydroxyurea and interferon therapy, among others.{{Cite web |title=Polycythemia vera - Diagnosis and treatment - Mayo Clinic |url=https://www.mayoclinic.org/diseases-conditions/polycythemia-vera/diagnosis-treatment/drc-20355855 |access-date=2022-03-11 |website=www.mayoclinic.org |language=en}} The tendency of some practitioners to avoid chemotherapy if possible, especially in young patients, is a result of research indicating possible increased risk of transformation to acute myelogenous leukemia (AML). While hydroxyurea is considered a safer chemotherapy in this aspect, there is still some debate about its long-term safety.{{cite journal|last1=Björkholm|first1=M|last2=Derolf|first2=AR|last3=Hultcrantz|first3=M|display-authors=etal|title=Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms.|journal=Journal of Clinical Oncology|date=10 June 2011|volume=29|issue=17|pages=2410–5|doi=10.1200/JCO.2011.34.7542|pmc=3107755|pmid=21537037}}

There are indications that the lung cancer drug erlotinib may be an additional treatment option for those with certain genetic markers.{{cite journal |vauthors=Li Z, Xu M, Xing S, Ho W, Ishii T, Li Q, Fu X, Zhao Z |title=Erlotinib Effectively Inhibits JAK2V617F Activity and Polycythemia Vera Cell Growth |journal=J Biol Chem |volume=282 |issue=6 |pages=3428–32 |year=2007 |pmid=17178722 |doi=10.1074/jbc.C600277200 |pmc=2096634|doi-access=free }}

Ruxolitinib (brand name Jakafi), a Janus kinase 2 (JAK2) inhibitor, is also used to treat polycythemia.{{cite journal|last1=Tefferi|first1=A|last2=Vannucchi|first2=AM|last3=Barbui|first3=T|title=Polycythemia vera treatment algorithm 2018.|journal=Blood Cancer Journal|date=10 January 2018|volume=8|issue=1|page=3|doi=10.1038/s41408-017-0042-7|pmid=29321547|pmc=5802495}}

Ropeginterferon alfa-2b (Besremi) was approved for medical use in the European Union in February 2019,{{cite web | title=Besremi EPAR | website=European Medicines Agency (EMA) | date=12 December 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/besremi | access-date=14 November 2021 }} and in the United States in November 2021.{{cite press release | title=FDA Approves Treatment for Rare Blood Disease | website=U.S. Food and Drug Administration (FDA) | date=12 November 2021 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-rare-blood-disease | archive-url=https://web.archive.org/web/20211112232607/http://www.fda.gov/news-events/press-announcements/fda-approves-treatment-rare-blood-disease | url-status=dead | archive-date=November 12, 2021 | access-date=12 November 2021}} {{PD-notice}}{{cite press release | title=U.S. FDA Approves Besremi (ropeginterferon alfa-2b-njft) as the Only Interferon for Adults With Polycythemia Vera | publisher=PharmaEssentia | via=Business Wire | date=12 November 2021 | url=https://www.businesswire.com/news/home/20211112005909/en/U.S.-FDA-Approves-BESREMi%C2%AE-ropeginterferon-alfa-2b-njft-as-the-Only-Interferon-for-Adults-With-Polycythemia-Vera | access-date=14 November 2021}} Ropeginterferon alfa-2b is the first medication approved by the U.S. Food and Drug Administration (FDA) to treat polycythemia vera that people can take regardless of their treatment history, and the first interferon therapy specifically approved for polycythemia vera. Interferon alfa-2b is also used.

A healthy lifestyle, including no smoking and avoidance of excessive weight, is also recommended.{{Cite web|url=https://www.cancerresearchuk.org/about-cancer/polycythaemia-vera/tests-treatment|title=Tests and treatment for polycythaemia vera (PV)|website=www.cancerresearchuk.org}}

A hematologist may be involved in the care of patients with PV.

Patient education and patient forums can help patients practically and emotionally manage a PV diagnosis, symptoms and other practical considerations.{{Cite web|url=https://www.macmillan.org.uk/cancer-information-and-support/blood-cancer/polycythaemia-vera-pv|title=Polycythaemia vera (PV) - Macmillan Cancer Support|website=www.macmillan.org.uk}}

Polycythemia vera occurs in all age groups,{{cite journal |vauthors=Passamonti F, Malabarba L, Orlandi E, Baratè C, Canevari A, Brusamolino E, Bonfichi M, Arcaini L, Caberlon S, Pascutto C, Lazzarino M | title = Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia | journal = Haematologica | volume = 88 | issue = 1 | pages = 13–8 | year = 2003 | pmid = 12551821}} although the incidence increases with age. One study found the median age at diagnosis to be 60 years,{{cite journal | author = Berlin NI | year = 1975 | title = Diagnosis and classification of polycythemias | journal = Semin Hematol | volume = 12 | issue = 4| pages = 339–51 | pmid = 1198126 }} and another that the highest incidence was in people aged 70–79 years.{{cite journal |vauthors=Anía B, Suman V, Sobell J, Codd M, Silverstein M, Melton L | title = Trends in the incidence of polycythemia vera among Olmsted County, Minnesota residents, 1935-1989 | journal = Am J Hematol | volume = 47 | issue = 2 | pages = 89–93 | year = 1994 | pmid = 8092146 | doi = 10.1002/ajh.2830470205| s2cid = 31536624 }} 10% of PV patients are below age 40 years.

Overall incidences in population studies have been 1.9/100,000 person-years in a Minnesota study, and

1.48/100,000 person-years in an age-standardized Swedish study (n = 6281). PV can impact all ethnic groups. There are slightly more cases in men than women.

A cluster around a toxic site was confirmed in northeast Pennsylvania in 2008.{{cite journal|author=MICHAEL RUBINKAM |title=Cancer cluster confirmed in northeast Pennsylvania |journal=Associated Press |url=https://news.yahoo.com/s/ap/20080826/ap_on_sc/toxic_dump_fears |year=2008 |archive-url=https://web.archive.org/web/20080902020159/http://news.yahoo.com/s/ap/20080826/ap_on_sc/toxic_dump_fears |archive-date=September 2, 2008 }}

• Phyllis George (1949–2020), American sportscaster and former First Lady of Kentucky{{cite news |last=Yetter |first=Deborah |date=May 16, 2020 |title=Phyllis George, former Kentucky first lady and Miss America, dies at 70 |url=https://www.courier-journal.com/story/news/local/2020/05/16/former-miss-america-kentucky-first-lady-phyllis-george-dies/3051644001/ |work=The Courier-Journal |access-date=May 16, 2020}}
• Chet Lemon (1955-2025), American baseball player{{cite news |author1=Jeff Seidel |author2=Evan Petzold |date=May 8, 2025 |title=Chet Lemon, 1984 Detroit Tigers hero, dies at age 70 |url=https://www.freep.com/story/sports/mlb/tigers/2025/05/08/chet-lemon-death-age-tigers-1984/83513931007/ |work=Detroit Free Press}}
• Ron Miles (1963–2022), American jazz trumpeter{{cite news |last=Harrington |first=Jim |date=March 9, 2022 |title='Gifted artist' Ron Miles dies of a rare blood disorder at 58 |url=https://www.mercurynews.com/2022/03/09/gifted-artist-ron-miles-dies-of-a-rare-blood-disorder-at-58/ |newspaper=The Mercury News |access-date=March 10, 2022}}
• Nell Rankin (1924–2005), American mezzo-soprano{{cite news |author=Allan Kozinn |date=January 19, 2005 |title=Nell Rankin Is Dead at 81; Mezzo-Soprano with Met |url=https://www.nytimes.com/2005/01/19/arts/music/19rankin.html |work=The New York Times}}

{{Reflist}}

• [https://www.nhlbi.nih.gov/health-topics/polycythemia-vera Polycythemia Vera] at the National Heart, Lung, and Blood Institute
• {{MerckManual|11|141|d}}

{{Medical resources

| DiseasesDB =

| ICD10 = {{ICD10|D|45||d|37}}

| ICD9 = {{ICD9|238.4}}

| ICDO = {{ICDO|9950|3}}

| OMIM =

| MedlinePlus = 000589

| eMedicineSubj =

| eMedicineTopic =

| MeshID = D011087

}}

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Category:Hematopathology

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