{"entity":{"id":"polycythaemia-vera","kind":"cancer","name":"Polycythaemia vera (PV)","aka":["Polycythemia vera","PV","Primary polycythaemia","Vaquez disease","Vaquez-Osler disease"],"tldr":"Polycythaemia vera is a slow blood cancer in which a single faulty gene, JAK2, makes the bone marrow produce too many red cells. Thick blood causes clots, so treatment thins it (blood removal, aspirin) and, for higher-risk patients, calms the marrow with hydroxyurea, interferon or ruxolitinib; a hepcidin mimic, rusfertide, now controls red cell counts without regular blood removal.","summary":"Polycythaemia vera is one of the classical myeloproliferative neoplasms. Almost every case carries a mutation in JAK2 (V617F in about 95 percent, exon 12 in most of the rest) that keeps the red-cell growth signal switched on without erythropoietin. The result is a high haematocrit, often with raised platelets and white cells, an enlarged spleen, itching after warm water, burning red hands and feet, and above all a raised risk of arterial and venous thrombosis, including clots in unusual places such as the hepatic veins. Diagnosis rests on the blood count, the JAK2 mutation, a hypercellular marrow and a low erythropoietin level. Treatment is risk-adapted: everyone has low-dose aspirin and phlebotomy to keep the haematocrit under 45 percent, a target proven by the CYTO-PV trial; people over 60 or with a prior clot add a cytoreductive drug, hydroxyurea or ropeginterferon alfa-2b, with ruxolitinib for those hydroxyurea fails. Rusfertide, a hepcidin mimetic that starves red-cell production of iron, was approved in 2026 for phlebotomy-dependent disease. Over decades a minority progress to post-PV myelofibrosis and a few percent to acute leukaemia, which is why the field is now chasing molecular remission with interferon and JAK2 V617F-selective inhibitors.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Polycythemia_vera","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Polycythemia_vera"},{"label":"MPN Research Foundation","url":"https://www.mpnresearchfoundation.org/polycythemia-vera/"},{"label":"NCI PDQ: chronic myeloproliferative neoplasms","url":"https://www.cancer.gov/types/myeloproliferative/patient/chronic-treatment-pdq"}],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"notes":[],"group":"haematologic","burden":"Around one to two new cases per 100,000 people a year, most diagnosed in their sixties; with treatment most people live for decades, and the main dangers are clots, bleeding and, late on, scarring of the marrow or leukaemia.","subtypes":["JAK2 V617F-positive (about 95 percent)","JAK2 exon 12-mutated (about 3 percent; often isolated erythrocytosis)","Masked PV (haemoglobin below the WHO threshold but marrow and mutation typical)","Post-PV myelofibrosis (spent phase)","PV in blast phase (transformation to acute myeloid leukaemia)"],"biomarkers":["JAK2 V617F allele burden (falls with interferon; a marker of molecular response)","JAK2 exon 12 mutations","Haematocrit, with treatment targeting below 45 percent","Serum erythropoietin (low in PV, high in secondary erythrocytosis)","Leukocyte count above 11 x 10^9/L (thrombosis risk)","Additional mutations in TET2, ASXL1, SRSF2, IDH1/2 (progression risk)","Age over 60 and prior thrombosis (the two risk factors that define high-risk disease)"],"standardOfCare":[{"setting":"Diagnosis","approach":"Full blood count, JAK2 V617F and exon 12 testing, serum erythropoietin, and bone marrow biopsy showing trilineage growth; WHO criteria (haemoglobin above 16.5 g/dL in men or 16.0 in women, or haematocrit above 49 or 48 percent). Secondary causes of a high red count (smoking, sleep apnoea, kidney or liver tumours, testosterone) are excluded first.","refs":["jak2","erythrocytosis"]},{"setting":"All patients","approach":"Low-dose aspirin unless contraindicated, phlebotomy to a haematocrit under 45 percent (CYTO-PV), and control of cardiovascular risk factors.","refs":["aspirin","cyto-pv","phlebotomy","haematocrit"]},{"setting":"Low risk (under 60, no prior clot)","approach":"Aspirin and phlebotomy alone; ropeginterferon alfa-2b is an option when phlebotomy is poorly tolerated or symptoms persist (Low-PV).","refs":["ropeginterferon-alfa-2b","low-pv"]},{"setting":"High risk (over 60 or prior clot)","approach":"Add cytoreduction: hydroxyurea, or ropeginterferon alfa-2b (PROUD-PV and CONTINUATION-PV), the latter preferred in younger patients and in pregnancy.","refs":["hydroxyurea","ropeginterferon-alfa-2b","proud-pv"]},{"setting":"Hydroxyurea resistance or intolerance","approach":"Ruxolitinib (RESPONSE, RESPONSE-2, MAJIC-PV) for haematocrit control, spleen shrinkage and symptom relief; interferon if not already tried.","refs":["ruxolitinib","response","response-2","majic-pv"]},{"setting":"Phlebotomy-dependent disease","approach":"Rusfertide, a hepcidin mimetic given by weekly injection, keeps the haematocrit under 45 percent and removes the need for phlebotomy in most patients (VERIFY).","refs":["rusfertide","verify","hepcidin"]},{"setting":"Itching and burning extremities","approach":"Antihistamines, aspirin for erythromelalgia, interferon or ruxolitinib for severe aquagenic pruritus.","refs":["aquagenic-pruritus","erythromelalgia"]},{"setting":"Post-PV myelofibrosis","approach":"Managed as myelofibrosis: JAK inhibitors for spleen and symptoms, momelotinib for anaemia, allogeneic stem cell transplant for fit higher-risk patients.","refs":["myeloproliferative-neoplasms","ruxolitinib","momelotinib","post-pv-myelofibrosis"]}],"stateOfArt":["Keeping the haematocrit under 45 percent cuts major clots and cardiovascular death to about a third, the single most important result in PV (CYTO-PV).","Ropeginterferon alfa-2b is the first drug shown to shrink the JAK2 mutant clone in a randomised trial, and its long-term molecular responses raise the prospect of changing the course of the disease rather than only controlling counts.","Ruxolitinib gives durable haematocrit and symptom control after hydroxyurea fails, and in MAJIC-PV a complete response tracked with fewer clots and progressions.","Rusfertide, approved in 2026, is the first mechanistically new PV drug in a decade: by mimicking hepcidin it starves red-cell production of iron and made three quarters of patients phlebotomy-free in VERIFY.","The unmet needs are a treatment that prevents progression to myelofibrosis and leukaemia, and a way to select who needs cytoreduction beyond age and clot history."],"history":[{"year":1892,"title":"Vaquez describes the disease","note":"Louis Henri Vaquez reports a patient with persistent excess red cells and an enlarged spleen.","refs":[]},{"year":1903,"title":"Osler defines a clinical syndrome","note":"William Osler collects cases of chronic cyanosis with polycythaemia and splenomegaly.","refs":[]},{"year":1951,"title":"Dameshek groups the myeloproliferative disorders","note":"PV, essential thrombocythaemia, myelofibrosis and CML proposed as related diseases of the marrow.","refs":["myeloproliferative-neoplasms"]},{"year":1967,"title":"Polycythemia Vera Study Group founded","note":"Louis Wasserman's cooperative group runs the first randomised PV trials, comparing phlebotomy, radiophosphorus and chlorambucil, and shows the leukaemia risk of alkylating agents.","refs":[]},{"year":2005,"title":"JAK2 V617F discovered","note":"Four groups report the mutation in almost all PV; the first molecular marker for BCR-ABL1-negative MPN and the target for the JAK inhibitors that followed.","refs":["jak2","jak2-v617f"]},{"year":2013,"title":"CYTO-PV proves the haematocrit target","note":"Keeping the haematocrit under 45 percent gives fewer cardiovascular deaths and major clots than a 45 to 50 percent target.","refs":["cyto-pv","haematocrit"]},{"year":2014,"title":"Ruxolitinib approved for PV","note":"FDA approval in December 2014 for hydroxyurea-resistant or intolerant PV on the RESPONSE trial; EU approval followed in 2015.","refs":["ruxolitinib","response"]},{"year":2019,"title":"Ropeginterferon alfa-2b approved in Europe","note":"The first interferon licensed for PV, on PROUD-PV and CONTINUATION-PV; FDA approval followed in November 2021.","refs":["ropeginterferon-alfa-2b","proud-pv"]},{"year":2021,"title":"Low-PV: interferon helps low-risk patients too","note":"Ropeginterferon plus phlebotomy kept more low-risk patients at target than phlebotomy alone.","refs":["low-pv"]},{"year":2023,"title":"MAJIC-PV links complete response to fewer events","note":"Ruxolitinib beat best available therapy after hydroxyurea failure, and complete responders had better event-free survival.","refs":["majic-pv","ruxolitinib"]},{"year":2025,"title":"VERIFY: a hepcidin mimetic replaces phlebotomy","note":"Rusfertide added to standard care made most patients phlebotomy-free over weeks 20 to 32.","refs":["verify","rusfertide"]},{"year":2026,"title":"Rusfertide approved","note":"FDA approval for phlebotomy-dependent polycythaemia vera.","refs":["rusfertide"]}],"pipeline":["givinostat","bomedemstat","nct06093672","idea-pv-clone-directed-therapy","idea-pv-hepcidin-first"],"openProblems":["No treatment has yet been shown to prevent progression to myelofibrosis or leukaemia; interferon's molecular responses are the strongest hint.","Risk stratification still rests on age and clot history; leukocyte count, allele burden and additional mutations are not yet built into treatment decisions.","Whether low-risk patients should have early cytoreduction (Low-PV suggests yes for interferon) remains unsettled and depends on cost and tolerability.","Aquagenic pruritus and fatigue are under-treated and poorly measured in trials.","Hepcidin mimetics control counts but their effect on thrombosis and long-term outcomes is not yet known."]},"route":"/cancers/polycythaemia-vera/","neighbours":{"cancer":[{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"}],"target":[{"id":"jak2","kind":"target","name":"JAK2","route":"/targets/jak2/"}],"term":[{"id":"aquagenic-pruritus","kind":"term","name":"Aquagenic pruritus","route":"/terms/aquagenic-pruritus/"},{"id":"erythrocytosis","kind":"term","name":"Erythrocytosis (primary vs secondary)","route":"/terms/erythrocytosis/"},{"id":"erythromelalgia","kind":"term","name":"Erythromelalgia","route":"/terms/erythromelalgia/"},{"id":"haematocrit","kind":"term","name":"Haematocrit","route":"/terms/haematocrit/"},{"id":"hepcidin","kind":"term","name":"Hepcidin","route":"/terms/hepcidin/"},{"id":"jak2-v617f","kind":"term","name":"JAK2 V617F","route":"/terms/jak2-v617f/"},{"id":"phlebotomy","kind":"term","name":"Phlebotomy (venesection)","route":"/terms/phlebotomy/"},{"id":"post-pv-myelofibrosis","kind":"term","name":"Post-PV myelofibrosis (spent phase)","route":"/terms/post-pv-myelofibrosis/"}],"trial":[{"id":"cyto-pv","kind":"trial","name":"CYTO-PV","route":"/trials/cyto-pv/"},{"id":"low-pv","kind":"trial","name":"Low-PV","route":"/trials/low-pv/"},{"id":"majic-pv","kind":"trial","name":"MAJIC-PV","route":"/trials/majic-pv/"},{"id":"proud-pv","kind":"trial","name":"PROUD-PV and CONTINUATION-PV","route":"/trials/proud-pv/"},{"id":"response","kind":"trial","name":"RESPONSE","route":"/trials/response/"},{"id":"response-2","kind":"trial","name":"RESPONSE-2","route":"/trials/response-2/"},{"id":"nct06093672","kind":"trial","name":"Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera","route":"/trials/nct06093672/"},{"id":"verify","kind":"trial","name":"VERIFY","route":"/trials/verify/"}],"drug":[{"id":"aspirin","kind":"drug","name":"Aspirin","route":"/drugs/aspirin/"},{"id":"bomedemstat","kind":"drug","name":"Bomedemstat","route":"/drugs/bomedemstat/"},{"id":"givinostat","kind":"drug","name":"Givinostat","route":"/drugs/givinostat/"},{"id":"hydroxyurea","kind":"drug","name":"Hydroxyurea (hydroxycarbamide)","route":"/drugs/hydroxyurea/"},{"id":"interferon-alfa","kind":"drug","name":"Interferon alfa-2a/2b","route":"/drugs/interferon-alfa/"},{"id":"momelotinib","kind":"drug","name":"Momelotinib","route":"/drugs/momelotinib/"},{"id":"peginterferon-alfa-2b","kind":"drug","name":"Peginterferon alfa-2b","route":"/drugs/peginterferon-alfa-2b/"},{"id":"ropeginterferon-alfa-2b","kind":"drug","name":"Ropeginterferon alfa-2b","route":"/drugs/ropeginterferon-alfa-2b/"},{"id":"rusfertide","kind":"drug","name":"Rusfertide","route":"/drugs/rusfertide/"},{"id":"ruxolitinib","kind":"drug","name":"Ruxolitinib","route":"/drugs/ruxolitinib/"}],"idea":[{"id":"idea-pv-clone-directed-therapy","kind":"idea","name":"Clearing the JAK2 clone in polycythaemia vera: interferon plus mutant-selective inhibitors as a route to treatment-free remission","route":"/ideas/idea-pv-clone-directed-therapy/"},{"id":"idea-pv-hepcidin-first","kind":"idea","name":"Hepcidin-based control as first-line treatment in low-risk polycythaemia vera","route":"/ideas/idea-pv-hepcidin-first/"}]}}