Polycythaemia Vera (PV)

📋 Key Information Summary

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Polycythaemia vera (PV) is a clonal myeloproliferative neoplasm driven by the JAK2 V617F mutation (95%) or, rarely, JAK2 exon 12 mutations, causing constitutive JAK-STAT activation and uncontrolled erythroid, myeloid, and megakaryocyte proliferation.
Major causes of morbidity and mortality are arterial and venous thrombosis (stroke, MI, portal vein thrombosis, DVT/PE) and transformation to secondary myelofibrosis (post-PV MF) or acute myeloid leukaemia (AML).
Diagnosis requires WHO 2022 criteria: Hb >165 g/L (males) or >160 g/L (females), or Hct >49% (males) or >48% (females), plus major criterion of BM hypercellularity with panmyelosis OR presence of JAK2 mutation.
JAK2 V617F mutation testing (peripheral blood) is the single most important diagnostic investigation and is available on MBS.
First-line therapy is venesection to maintain Hct <45% combined with low-dose aspirin (75–100 mg daily) in all patients unless contraindicated.
Cytoreduction with hydroxycarbamide (hydroxyurea, Hydrea®) is indicated for high-risk patients (age >60 or prior thrombosis) and selected intermediate-risk patients.
Ruxolitinib (Jakavi®) is second-line cytoreductive therapy for hydroxycarbamide intolerance/resistance and is PBS Authority Required.
Risk stratification drives treatment intensity: low-risk patients receive phlebotomy + aspirin only; high-risk patients require cytoreduction.
Key safety alert: uncontrolled PV (Hct >52%) dramatically increases thrombotic risk; every effort must be made to maintain Hct <45%.
Aboriginal and Torres Strait Islander peoples may have higher burden of cardiovascular risk factors compounding PV-related thrombosis risk; culturally safe, community-based follow-up is essential.
Monitor for disease transformation — worsening constitutional symptoms, increasing splenomegaly, or new cytopenias should prompt reassessment for post-PV myelofibrosis or AML.
Pregnancy requires specialist haematology input; venesection and low-dose aspirin are generally continued; interferon-alpha is the preferred cytoreductive agent if required.

Introduction & Australian Epidemiology

Polycythaemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterised by clonal proliferation of haematopoietic precursors, leading to erythrocytosis with or without leucocytosis and thrombocytosis. It is one of three classical Philadelphia-chromosome-negative MPNs, alongside essential thrombocythaemia (ET) and primary myelofibrosis (PMF).

In Australia, PV accounts for approximately 2–3 new diagnoses per 100,000 population per year. The median age at diagnosis is 60–65 years, with a slight male predominance (M:F ratio approximately 1.2:1). The disease is rare under 40 years of age, though JAK2 exon 12-mutated PV can present earlier. Australian registry data from Cancer Council Victoria and the AIHW confirm that PV incidence is rising in parallel with increased use of routine full blood count (FBC) screening and JAK2 mutation testing in general practice.

The principal clinical concern in PV is thrombotic complication, which accounts for approximately 40–50% of deaths. In the landmark CYTO-PV trial, patients randomised to a haematocrit (Hct) target of <45% had significantly fewer major thrombotic events and cardiovascular deaths compared with those maintained at 45–50%. This finding underpins the current therapeutic standard of maintaining Hct <45% in all patients with PV.

With appropriate treatment, median survival in PV exceeds 15–20 years, though this is still reduced compared with the age-matched general population. Transformation to secondary myelofibrosis occurs in approximately 10–15% of patients over 10–15 years, and progression to AML in 2–5%.

Pathogenesis — JAK2 V617F Mutation

The pathogenesis of PV is driven by somatic mutations in the Janus kinase 2 (JAK2) gene, which encodes a cytoplasmic tyrosine kinase essential for haematopoietic growth factor receptor signalling. Two mutation types are recognised:

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JAK2 V617F

Found in >95% of PV cases

Mutation type Somatic point mutation: G→T at nucleotide 1849 (exon 14), causing valine-to-phenylalanine substitution at codon 617 in the pseudokinase (JH2) domain

Functional effect Loss of autoinhibitory function of JH2 domain → constitutive activation of the JH1 kinase domain → ligand-independent activation of JAK-STAT, PI3K/AKT, and MAPK/ERK signalling pathways

Clonality Present in erythroid, myeloid, and megakaryocyte lineages; confirms the stem cell origin of PV

🧬

JAK2 Exon 12 Mutations

Found in 2–3% of PV (V617F-negative cases)

Mutation types In-frame deletions, insertions, or point mutations in exon 12 (e.g., N542-E543del, E543-D544del, F537-K539delinsL)

Clinical phenotype Isolated erythrocytosis without significant leucocytosis or thrombocytosis at presentation; often younger patients; lower allele burden

Detection Requires specific testing — standard JAK2 V617F PCR will be negative; request "JAK2 exon 12 panel" or next-generation sequencing

Downstream Consequences of JAK2 Activation

Erythropoietin-independent erythropoiesis: Mutant JAK2 mimics constitutive EPO receptor signalling, causing erythroid progenitor proliferation independent of erythropoietin levels. Serum EPO is characteristically low.
Thrombopoietin-independent thrombopoiesis: Megakaryocyte proliferation is driven by constitutive TPO receptor signalling.
Granulocyte proliferation: Myeloid expansion contributes to leucocytosis in many patients.
Increased neutrophil-platelet interaction: Activated leucocytes and platelets promote a prothrombotic milieu, explaining the disproportionate thrombosis risk relative to Hct alone.
Low serum EPO: A key distinguishing feature from secondary (reactive) polycythaemia, where EPO is normal or elevated.

Additional Somatic Mutations

Co-mutations in epigenetic regulators (TET2, ASXL1, DNMT3A, EZH2) and spliceosome genes (SRSF2) are found in 20–40% of PV patients and may influence disease phenotype, thrombosis risk, and transformation risk. Mutations in ASXL1, SRSF2, IDH1/2, and RUNX1 are associated with inferior survival and higher rates of leukaemic transformation.

Clinical Features & WHO 2022 Diagnostic Criteria

Clinical Presentation

Approximately 30–40% of PV patients are asymptomatic at diagnosis, detected incidentally on FBC. Symptomatic patients may present with:

Headache, visual disturbance (scintillating scotomata), dizziness, tinnitus: due to hyperviscosity
Plethora (ruddy cyanosis): facial and conjunctival erythema — a classic but not universal sign
Aquagenic pruritus: intense itching after warm bathing or showering, occurs in 40–65% of patients; pathognomonic when present
Erythromelalgia: burning pain and erythema of the extremities (typically hands/feet); caused by platelet-mediated arteriolar microthrombi
Splenomegaly: present in 40–70% at diagnosis; hepatomegaly in 30–40%
Fatigue, night sweats, weight loss: constitutional symptoms present in ~30%
Thrombotic events: stroke, TIA, MI, peripheral arterial thrombosis, portal vein thrombosis (Budd-Chiari syndrome), mesenteric vein thrombosis, DVT, PE
Haemorrhagic events: paradoxically, bleeding (gum bleeding, epistaxis, GI haemorrhage) may occur due to acquired von Willebrand syndrome at very high platelet counts (>1000 × 10⁹/L)
Gout: secondary hyperuricaemia from increased cell turnover

⚠️

Budd-Chiari syndrome and portal vein thrombosis may be the presenting feature of occult PV. Always request JAK2 V617F testing in unexplained hepatic vein or portal vein thrombosis, even in the absence of overt erythrocytosis.

WHO 2022 Diagnostic Criteria for PV

The diagnosis of PV requires meeting all three major criteria, or the first two major criteria plus the minor criterion.

Criterion	Requirement
Major criterion 1 — Haemoglobin/Hct threshold	Hb >165 g/L (males) or >160 g/L (females) OR Hct >49% (males) or >48% (females)
Major criterion 2 — Bone marrow biopsy	Hypercellularity for age with panmyelosis (erythroid, granulocytic, and megakaryocytic proliferation). Grading of reticulin fibrosis (grade 0–1 recommended at diagnosis).
Major criterion 3 — JAK2 mutation	Presence of JAK2 V617F mutation or JAK2 exon 12 mutation
Minor criterion	Subnormal serum erythropoietin level

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Diagnostic shortcut: In clinical practice, a patient with Hb >165 g/L (♂) or >160 g/L (♀) plus a positive JAK2 V617F mutation virtually always has PV. Bone marrow biopsy confirms the diagnosis and provides baseline reticulin fibrosis grading, which is important for prognostication and future disease monitoring.

Investigations

Investigation follows a structured approach: confirm erythrocytosis, exclude reactive causes, establish clonality, and risk-stratify.

Laboratory Investigations

ESSENTIAL

Full Blood Count (FBC) with differential

Elevated Hb/Hct, often leucocytosis and/or thrombocytosis. Baseline for all subsequent monitoring. MBS item 65070.

ESSENTIAL

JAK2 V617F Mutation Analysis

Peripheral blood PCR. Sensitivity >97% for PV. If negative, request JAK2 exon 12 panel. MBS item 73302 (JAK2 V617F). Must be ordered by a specialist.

ESSENTIAL

Serum Erythropoietin (EPO) Level

Subnormal in PV (<4 IU/L in ~85% of cases). Normal or elevated in secondary/reactive polycythaemia. MBS item 66835.

ESSENTIAL

Ferritin, Iron Studies, B₁₂, Folate

Ferritin often low due to expanded red cell mass. B₁₂ may be elevated (from increased transcobalamin production). Iron studies essential to guide venesection therapy.

AVAILABLE

Lactate Dehydrogenase (LDH), Urate

Elevated in PV due to increased cell turnover. Useful for baseline and disease monitoring. MBS items 66547 (LDH), 66552 (urate).

AVAILABLE

Peripheral Blood Film

May show tear-drop poikilocytes, nucleated red cells, leucoerythroblastosis — features suggesting myelofibrotic transformation.

SPECIALIST

Bone Marrow Biopsy with Cytogenetics

Confirms panmyelosis, grades reticulin fibrosis (MF-0 to MF-3), and provides cytogenetic analysis. Mandatory per WHO 2022 criteria. Baseline trephine should be retained for future comparison.

SPECIALIST

Next-Generation Sequencing (NGS) MPN Panel

Assesses additional mutations (ASXL1, TET2, DNMT3A, SRSF2, IDH1/2, EZH2, RUNX1). Prognostic value — certain mutation combinations confer higher transformation risk. Not yet routine in all Australian centres.

AVAILABLE

Venous Blood Gas (SpO₂ + Carboxyhaemoglobin)

To exclude secondary causes — chronic hypoxaemia (COPD, OSA, cyanotic heart disease) and carboxyhaemoglobinaemia (smoking).

Excluding Reactive (Secondary) Polycythaemia

⚠️

Before diagnosing PV, exclude common causes of reactive erythrocytosis: obstructive sleep apnoea (polysomnography referral), chronic smoking (carboxyhaemoglobin), testosterone therapy, chronic hypoxia (COPD, high-altitude residence), and renal causes (renal artery stenosis, post-renal transplant EPO production). Testosterone replacement is an increasingly common cause of isolated erythrocytosis in Australian men.

Imaging

Abdominal ultrasound: Assess spleen size (normal <13 cm craniocaudal length). Document hepatomegaly. MBS item 55043.
Cross-sectional imaging (CT/MRI): If ultrasound findings equivocal or to assess for thrombotic complications (portal vein, hepatic veins, mesenteric veins).

Risk Stratification

Risk stratification in PV determines treatment intensity. The conventional two-tier model classifies patients as low-risk or high-risk based on age and thrombosis history. More recent models incorporate additional cardiovascular risk factors.

Low Risk

Venesection + Aspirin Only

Age <60 years AND no prior thrombosis (arterial or venous). May include patients without additional cardiovascular risk factors (diabetes, hypertension, smoking, dyslipidaemia).

Setting: Haematologist-led with GP shared care; venesection in hospital or community setting

Intermediate Risk

Consider Cytoreduction

Age <60 with no thrombosis BUT ≥1 cardiovascular risk factor (hypertension, diabetes, smoking, dyslipidaemia). Worsening disease burden (progressive splenomegaly, uncontrolled symptoms, high phlebotomy requirement >3–4 per year).

Setting: Specialist haematology review; individualised decision on cytoreduction

High Risk

Venesection + Aspirin + Cytoreduction

Age ≥60 years OR history of prior thrombosis (arterial or venous). These patients have a significantly elevated thrombotic risk and require cytoreductive therapy regardless of symptom burden.

Setting: Haematologist-managed; cytoreduction with hydroxycarbamide first-line

🚨

High-risk patients who do not receive cytoreduction have a substantially increased risk of major thrombotic events (stroke, MI, PE). Ensure all high-risk patients are commenced on cytoreductive therapy and document the indication.

Management

Management of PV has three pillars: (1) reduction of Hct to <45% via venesection, (2) antiplatelet therapy with low-dose aspirin, and (3) cytoreductive therapy for high-risk and selected intermediate-risk patients.

Pillar 1 — Venesection (Phlebotomy)

Venesection is the cornerstone of PV therapy and is indicated in all patients. The target Hct is <45%, based on the CYTO-PV trial (Marchioli et al., NEJM 2013).

Initial phase: Venesection of 450 mL (or 250 mL for patients <50 kg) every 1–2 weeks until Hct <45%.
Maintenance phase: Venesection every 2–3 months to maintain Hct <45%. Frequency guided by FBC monitoring.
Iron depletion: Repeated venesection inevitably leads to iron deficiency. This is expected and generally well tolerated. Do not supplement iron unless clinically symptomatic.
Logistics: Venesection can be performed in hospital day units, community pathology centres, or via Australian Red Cross Lifeblood (where eligible). MBS item 13700 (therapeutic venesection).

ℹ️

Key point from CYTO-PV: Patients randomised to Hct <45% had a significantly lower rate of cardiovascular death and major thrombosis (HR 0.69; 95% CI 0.53–0.91) compared with those maintained at 45–50%. This target is non-negotiable.

Pillar 2 — Low-Dose Aspirin

Low-dose aspirin (75–100 mg daily) is recommended for all patients with PV unless contraindicated, based on the ECLAP trial (Landolfi et al., NEJM 2004). Aspirin reduces the risk of arterial and venous thrombotic events by approximately 60%.

Dose: 75–100 mg orally once daily (e.g., Aspirin 100 mg, Cartia®).
Contraindications: Active bleeding, history of GI haemorrhage (unless on PPI), severe uncontrolled hypertension, platelet count >1500 × 10⁹/L (risk of acquired vWD bleeding), aspirin allergy.
Acquired von Willebrand syndrome: At very high platelet counts (>1000 × 10⁹/L), acquired vWD may develop. Consider checking vWF antigen/activity before commencing aspirin if platelets >1000 × 10⁹/L.
PBS status: General Benefit (over-the-counter in Australia).

Pillar 3 — Cytoreductive Therapy

Cytoreduction is indicated for high-risk patients (age ≥60 or prior thrombosis) and may be considered for intermediate-risk patients with inadequate disease control on venesection alone.

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Hydroxycarbamide (Hydroxyurea)

Hydrea® · Droxia® · Antimetabolite

Adult dose 15–20 mg/kg/day orally (typically 500 mg BD–TDS or 1 g BD for a 70 kg patient). Titrate to target Hct <45% and platelet <400 × 10⁹/L.

Paediatric dose Not established; specialist management required

Route / frequency Oral, once or twice daily, continuous

Renal adjustment Reduce dose in severe renal impairment (eGFR <30 mL/min). Monitor FBC closely.

Hepatic adjustment Use with caution; no formal dose adjustment but monitor closely

Adverse effects Myelosuppression (neutropenia, anaemia), macrocytosis, leg ulcers, oral ulcers, skin hyperpigmentation, GI disturbance. Teratogenic — effective contraception required.

PBS status ✔ PBS General Benefit

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Ruxolitinib

Jakavi® · JAK1/JAK2 Inhibitor

Adult dose 10 mg orally twice daily. May increase to 25 mg BD if inadequate response after 3 months. Reduce to 5 mg BD if cytopenias develop.

Indication Second-line: hydroxycarbamide-resistant or hydroxycarbamide-intolerant PV (RESPONSE and RESPONSE-2 trials). Significant reduction in spleen size and phlebotomy requirement.

Renal adjustment eGFR 30–59: start 10 mg BD; eGFR 15–29: 5 mg BD (with close monitoring); eGFR <15: avoid use

Hepatic adjustment Child-Pugh A: no adjustment. Child-Pugh B: reduce to 10 mg BD (for starting dose of 15 mg BD); avoid if Child-Pugh C.

Adverse effects Anaemia, thrombocytopenia, neutropenia, increased infection risk (herpes zoster reactivation — consider varicella vaccination prior), weight gain, hyperlipidaemia, dizziness.

PBS status ⚠ PBS Authority Required — Resistant or intolerant to hydroxycarbamide; specialist initiation

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Pegylated Interferon Alfa-2a

Pegasys® · Immunomodulator

Adult dose 45 μg subcutaneously once weekly (reduced from 90 μg to minimise side effects). May increase to 90 μg weekly if tolerated and needed.

Indication Alternative first-line cytoreductor, especially in younger patients (<60), pregnancy planning, or if concerns about leukaemogenic potential of hydroxycarbamide. May achieve molecular responses (JAK2 V617F allele burden reduction).

Adverse effects Flu-like symptoms, fatigue, depression, cytopenias, autoimmune thyroiditis, injection-site reactions. Pre-medicate with paracetamol for flu-like symptoms.

PBS status PBS Restricted Benefit — Authority for PV where hydroxycarbamide unsuitable

Symptomatic Management

Symptom	Management
Aquagenic pruritus	Cetirizine 10 mg OD; paroxetine 20 mg OD (off-label); narrowband UVB phototherapy; aspirin may help; ruxolitinib is particularly effective
Erythromelalgia	Low-dose aspirin is highly effective (often resolves within hours); also control Hct and platelet count
Gout / hyperuricaemia	Allopurinol 100–300 mg OD; colchicine 0.5 mg for acute flares (renal adjustment required)
Fatigue	Optimise Hct; rule out iron deficiency; graded exercise programme; consider ruxolitinib if refractory
Splenomegaly discomfort	Cytoreduction; avoid contact sports; ruxolitinib for refractory splenomegaly

Monitoring

Lifelong monitoring is essential in PV. The frequency and intensity of monitoring depends on disease phase, risk category, and treatment.

Every 1–3 months

FBC with differential: Core monitoring parameter. Target Hct <45%. Monitor for cytopenias if on cytoreduction. Assess platelet trend.

Every 3–6 months

Clinical review: Assess symptoms (pruritus, fatigue, splenic pain, visual symptoms), spleen size on palpation, medication side effects, cardiovascular risk factor review.

Every 6–12 months

Ferritin, LDH, urate: Monitor iron stores (expect falling ferritin with venesection), cell turnover markers.

Annually

Cardiovascular risk assessment: BP, HbA1c, lipids, smoking status. Reinforce thrombosis risk reduction (exercise, weight, alcohol moderation). JAK2 V617F allele burden (trend may indicate disease trajectory).

As clinically indicated

Bone marrow biopsy repeat: Indicated if features of disease transformation — progressive splenomegaly, new cytopenias, increasing LDH, peripheral blood film changes (tear-drop cells, leucoerythroblastosis). Assesses for fibrotic or leukaemic transformation. Also consider NGS panel for emerging high-risk mutations.

⚠️

Red flags requiring urgent reassessment: Rapidly enlarging spleen, falling Hb with rising LDH, increasing constitutional symptoms, new circulating blasts, or unexplained cytopenias — these suggest transformation to post-PV myelofibrosis or AML and require urgent specialist review and bone marrow assessment.

Special Populations

🤰 Pregnancy

Venesection:

Continue to maintain Hct <45%. Avoid aggressive venesection in third trimester — risk of fetal compromise.

Aspirin:

Low-dose aspirin (75–100 mg) generally continued throughout pregnancy unless active bleeding. Aspirin is safe in pregnancy.

Cytoreduction:

Hydroxycarbamide is teratogenic — must be discontinued 3–6 months before conception. Interferon-alpha (peginterferon alfa-2a) is the preferred cytoreductive agent in pregnancy. Specialist haematology-obstetric co-management is essential.

👶 Paediatrics

General:

PV is exceedingly rare in children. JAK2 exon 12 mutations are proportionally more common in paediatric PV. Management is by paediatric haematologist at a tertiary centre.

Venesection:

Volumes adjusted to body weight (typically 5–10 mL/kg). May require sedation or GA for young children.

👴 Elderly (≥75 years)

Aspirin risk:

Higher GI bleeding risk. Consider PPI co-prescription (e.g., pantoprazole 20 mg OD). Reassess aspirin if recurrent bleeding.

Venesection:

Venesection volumes may need to be reduced (250 mL). Monitor for symptomatic anaemia (iron depletion may cause fatigue, dyspnoea).

Cytoreduction:

Hydroxycarbamide preferred. Start at lower dose (500 mg BD) and titrate. Watch for myelosuppression.

🫘 Renal Impairment

Hydroxycarbamide:

Reduce dose if eGFR <30 mL/min. Monitor FBC more frequently.

Ruxolitinib:

eGFR 30–59: start 10 mg BD. eGFR 15–29: start 5 mg BD with close monitoring. Avoid if eGFR <15.

Allopurinol:

Dose adjust for gout treatment: eGFR 10–20: 100 mg every 2–3 days; eGFR <10: 100 mg every 3 days.

🫁 Hepatic Impairment

Ruxolitinib:

Child-Pugh A: no adjustment. Child-Pugh B: reduce dose (start 10 mg BD for 15 mg BD regimen). Avoid in Child-Pugh C.

Hydroxycarbamide:

Use cautiously; monitor liver function tests. No formal dose adjustment.

🛡️ Immunocompromised

Ruxolitinib:

Increased infection risk — particularly herpes zoster. Consider varicella zoster vaccination (Shingrix®) prior to initiation. Screen for latent TB. Monitor for opportunistic infections.

Hydroxycarbamide:

Neutropenia risk — monitor FBC regularly. Consider G-CSF if persistent neutropenia and recurrent infection.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

While PV is not known to be more prevalent in Aboriginal and Torres Strait Islander peoples, the management of PV is significantly influenced by the higher background prevalence of cardiovascular risk factors, limited specialist access in remote communities, and culturally specific health considerations.

Cardiovascular risk

ATSI peoples have a 1.7× age-standardised rate of cardiovascular disease compared with non-Indigenous Australians (AIHW 2023). This compounds PV-related thrombosis risk. Aggressive cardiovascular risk factor management (BP, lipids, diabetes, smoking cessation) is essential.

Remote and regional access

Venesection requires a facility with trained staff. In remote communities, venesection may be performed at the local health clinic, Aboriginal Medical Service (AMS), or via RFDS. Telehealth haematology review can supplement specialist input. Cytoreductive medication monitoring (FBC) can be performed at community health centres.

Culturally safe care

Ensure communication is culturally appropriate. Use Aboriginal Health Workers and liaison officers. Acknowledge the impact of intergenerational trauma and racism on health engagement. Respect kinship obligations and gender-sensitive care practices.

Medication adherence

Hydroxycarbamide is a PBS General Benefit medication and is affordable. Ensure understanding of daily dosing and importance of regular blood tests. Use Blister packs or Webster-paks. Coordinate with AMS pharmacy services.

Smoking and alcohol

Smoking is a major modifiable thrombosis risk factor. Offer Tackling Indigenous Smoking (TIS) programme referral. Alcohol excess may contribute to liver disease, nutritional deficiency, and poor medication adherence. Screen using AUDIT-C.

Follow-up continuity

Mobility between communities may disrupt regular follow-up. Use shared care models between AMS, remote GPs, and regional/rural haematologists. MBS-funded Aboriginal Health Assessments (item 715) can be leveraged for PV monitoring coordination.

📚 References

1. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22–33. doi:10.1056/NEJMoa1208500
2. Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004;350(2):114–124. doi:10.1056/NEJMoa035572
3. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426–435. doi:10.1056/NEJMoa1409002
4. Passamonti F, Griesshammer M, Palandri F, et al. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017;18(1):88–99. doi:10.1016/S1470-2045(16)30558-7
5. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36(7):1703–1719. doi:10.1038/s41375-022-01613-1
6. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2024;99(3):475–494. doi:10.1002/ajh.27189
7. Barbui T, Vannucchi AM, Buxhofer-Ausch V, et al. Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J. 2015;5(11):e369. doi:10.1038/bcj.2015.94
8. Australian Institute of Health and Welfare (AIHW). Cardiovascular disease in Aboriginal and Torres Strait Islander people. Cat. no. CVD 80. Canberra: AIHW; 2023.
9. Geyer HL, Scherber RM, Kosiorek H, et al. Symptomatic profiles of patients with polycythemia vera: implications of inadequately controlled disease. J Clin Oncol. 2016;34(2):151–159. doi:10.1200/JCO.2015.62.9337
10. McMullin MF, Harrison CN, Ali S, et al. A guideline for the diagnosis and management of polycythaemia vera. A British Society for Haematology guideline. Br J Haematol. 2019;184(2):176–191. doi:10.1111/bjh.15648
11. Grunwald MR, Burke JM, Kuter DJ, et al. Real-world risk assessment and treatment patterns in patients with polycythemia vera. Ann Hematol. 2022;101(3):581–590. doi:10.1007/s00277-021-04727-x
12. Spivak JL. Polycythemia vera: myths, mechanisms, and management. Blood. 2002;100(13):4272–4290. doi:10.1182/blood-2001-12-0349