# Polycythaemia vera (PV)

Source: https://onco.cc/cancers/polycythaemia-vera/  
OnCo record `polycythaemia-vera` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-16
- Also known as: Polycythemia vera; PV; Primary polycythaemia; Vaquez disease; Vaquez-Osler disease
- Tags: polycythaemia-vera; mpn
- 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)

## Standard of care

- Diagnosis: 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. ([JAK2](https://onco.cc/targets/jak2/), [Erythrocytosis (primary vs secondary)](https://onco.cc/terms/erythrocytosis/))
- All patients: Low-dose aspirin unless contraindicated, phlebotomy to a haematocrit under 45 percent (CYTO-PV), and control of cardiovascular risk factors. ([Aspirin](https://onco.cc/drugs/aspirin/), [CYTO-PV](https://onco.cc/trials/cyto-pv/), [Phlebotomy (venesection)](https://onco.cc/terms/phlebotomy/), [Haematocrit](https://onco.cc/terms/haematocrit/))
- Low risk (under 60, no prior clot): Aspirin and phlebotomy alone; ropeginterferon alfa-2b is an option when phlebotomy is poorly tolerated or symptoms persist (Low-PV). ([Ropeginterferon alfa-2b](https://onco.cc/drugs/ropeginterferon-alfa-2b/), [Low-PV](https://onco.cc/trials/low-pv/))
- High risk (over 60 or prior clot): Add cytoreduction: hydroxyurea, or ropeginterferon alfa-2b (PROUD-PV and CONTINUATION-PV), the latter preferred in younger patients and in pregnancy. ([Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Ropeginterferon alfa-2b](https://onco.cc/drugs/ropeginterferon-alfa-2b/), [PROUD-PV and CONTINUATION-PV](https://onco.cc/trials/proud-pv/))
- Hydroxyurea resistance or intolerance: Ruxolitinib (RESPONSE, RESPONSE-2, MAJIC-PV) for haematocrit control, spleen shrinkage and symptom relief; interferon if not already tried. ([Ruxolitinib](https://onco.cc/drugs/ruxolitinib/), [RESPONSE](https://onco.cc/trials/response/), [RESPONSE-2](https://onco.cc/trials/response-2/), [MAJIC-PV](https://onco.cc/trials/majic-pv/))
- Phlebotomy-dependent disease: Rusfertide, a hepcidin mimetic given by weekly injection, keeps the haematocrit under 45 percent and removes the need for phlebotomy in most patients (VERIFY). ([Rusfertide](https://onco.cc/drugs/rusfertide/), [VERIFY](https://onco.cc/trials/verify/), [Hepcidin](https://onco.cc/terms/hepcidin/))
- Itching and burning extremities: Antihistamines, aspirin for erythromelalgia, interferon or ruxolitinib for severe aquagenic pruritus. ([Aquagenic pruritus](https://onco.cc/terms/aquagenic-pruritus/), [Erythromelalgia](https://onco.cc/terms/erythromelalgia/))
- Post-PV myelofibrosis: Managed as myelofibrosis: JAK inhibitors for spleen and symptoms, momelotinib for anaemia, allogeneic stem cell transplant for fit higher-risk patients. ([Myeloproliferative neoplasms (PV, ET, myelofibrosis)](https://onco.cc/cancers/myeloproliferative-neoplasms/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/), [Momelotinib](https://onco.cc/drugs/momelotinib/), [Post-PV myelofibrosis (spent phase)](https://onco.cc/terms/post-pv-myelofibrosis/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Polycythemia_vera
- Wikipedia: https://en.wikipedia.org/wiki/Polycythemia_vera
- MPN Research Foundation: https://www.mpnresearchfoundation.org/polycythemia-vera/
- NCI PDQ: chronic myeloproliferative neoplasms: https://www.cancer.gov/types/myeloproliferative/patient/chronic-treatment-pdq

## Connected records

- cancers: [Myeloproliferative neoplasms (PV, ET, myelofibrosis)](https://onco.cc/cancers/myeloproliferative-neoplasms/)
- targets: [JAK2](https://onco.cc/targets/jak2/)
- terms: [Aquagenic pruritus](https://onco.cc/terms/aquagenic-pruritus/), [Erythrocytosis (primary vs secondary)](https://onco.cc/terms/erythrocytosis/), [Erythromelalgia](https://onco.cc/terms/erythromelalgia/), [Haematocrit](https://onco.cc/terms/haematocrit/), [Hepcidin](https://onco.cc/terms/hepcidin/), [JAK2 V617F](https://onco.cc/terms/jak2-v617f/), [Phlebotomy (venesection)](https://onco.cc/terms/phlebotomy/), [Post-PV myelofibrosis (spent phase)](https://onco.cc/terms/post-pv-myelofibrosis/)
- trials: [CYTO-PV](https://onco.cc/trials/cyto-pv/), [Low-PV](https://onco.cc/trials/low-pv/), [MAJIC-PV](https://onco.cc/trials/majic-pv/), [PROUD-PV and CONTINUATION-PV](https://onco.cc/trials/proud-pv/), [RESPONSE](https://onco.cc/trials/response/), [RESPONSE-2](https://onco.cc/trials/response-2/), [Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera](https://onco.cc/trials/nct06093672/), [VERIFY](https://onco.cc/trials/verify/)
- drugs: [Aspirin](https://onco.cc/drugs/aspirin/), [Bomedemstat](https://onco.cc/drugs/bomedemstat/), [Givinostat](https://onco.cc/drugs/givinostat/), [Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/), [Momelotinib](https://onco.cc/drugs/momelotinib/), [Peginterferon alfa-2b](https://onco.cc/drugs/peginterferon-alfa-2b/), [Ropeginterferon alfa-2b](https://onco.cc/drugs/ropeginterferon-alfa-2b/), [Rusfertide](https://onco.cc/drugs/rusfertide/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/)
- ideas: [Clearing the JAK2 clone in polycythaemia vera: interferon plus mutant-selective inhibitors as a route to treatment-free remission](https://onco.cc/ideas/idea-pv-clone-directed-therapy/), [Hepcidin-based control as first-line treatment in low-risk polycythaemia vera](https://onco.cc/ideas/idea-pv-hepcidin-first/)

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