📋 Key Information Summary
- Confirm true erythrocytosis by repeating FBC on two occasions; use sex-specific thresholds — haemoglobin >170 g/L or haematocrit >0.54 in men, haemoglobin >155 g/L or haematocrit >0.47 in women (WHO 2016 criteria).
- Secondary causes are far more common than polycythaemia vera (PV); always exclude chronic hypoxia (COPD, OSA, obstructive sleep apnoea), high altitude, smoking, testosterone/androgen therapy, and erythropoietin-secreting tumours before considering a primary marrow disorder.
- Measure serum erythropoietin (EPO) as the pivotal discriminator — a low or inappropriately normal EPO in the setting of erythrocytosis suggests a primary marrow process (PV), whereas an elevated EPO points to a secondary cause.
- Test for JAK2 V617F mutation in all patients with suspected primary erythrocytosis; it is present in ~95–97% of PV cases. If negative but PV still suspected, order JAK2 exon 12 mutation analysis (~3% of PV cases).
- WHO 2016 diagnostic criteria for PV require: (1) elevated Hb/Hct (major criterion 1), (2) bone marrow biopsy showing hypercellularity with trilineage growth (major criterion 2), and (3) JAK2 V617F or exon 12 mutation (major criterion 3); plus a minor criterion (subnormal serum EPO level) if only one major criterion is met.
- Thrombotic risk is the primary concern in PV — arterial thrombosis (stroke, MI, TIA) and venous thromboembolism (DVT, PE, splanchnic vein thrombosis, Budd-Chiari syndrome) account for most morbidity and mortality.
- First-line PV management includes low-dose aspirin (100 mg daily) and target haematocrit <0.45 via regular venesection; high-risk patients (age ≥60 or prior thrombosis) require cytoreductive therapy with hydroxycarbamide (hydroxyurea).
- Splenomegaly, aquagenic pruritus (itching triggered by hot water), erythromelalgia, and hyperviscosity symptoms (headache, visual disturbance, tinnitus) are characteristic clinical features that should prompt urgent workup.
- Refer to haematology for confirmed JAK2-positive erythrocytosis, unexplained persistent erythrocytosis, suspected hyperviscosity syndrome, splanchnic vein thrombosis with elevated Hct, or need for bone marrow biopsy.
- Aboriginal and Torres Strait Islander Australians may present with higher disease burden due to delayed diagnosis, limited specialist access in remote regions, and higher prevalence of comorbid conditions (e.g. smoking, COPD) contributing to secondary erythrocytosis.
- Testosterone and androgen therapy is an increasingly recognised iatrogenic cause of erythrocytosis — monitor FBC regularly in men receiving testosterone replacement therapy (TRT).
- Avoid therapeutic phlebotomy targets above 0.45 — the landmark CYTO-PV trial demonstrated that maintaining Hct <0.45 significantly reduces cardiovascular death and major thrombosis in PV patients.
Introduction & Australian Epidemiology
Polycythaemia (erythrocytosis) refers to an abnormally elevated red blood cell mass, defined by haemoglobin concentration or haematocrit exceeding sex-specific reference ranges. It encompasses a spectrum of disorders ranging from benign reactive (secondary) causes to clonal myeloproliferative neoplasms, principally polycythaemia vera (PV). Accurate classification is critical because management strategies, prognosis, and thrombotic risk differ substantially between primary and secondary aetiologies.
In Australia, PV is the most common Philadelphia chromosome-negative myeloproliferative neoplasm, with an estimated annual incidence of 2–3 per 100,000 population. The median age at diagnosis is 60–70 years, with a slight male predominance (male-to-female ratio approximately 1.2:1). However, secondary erythrocytosis is considerably more prevalent and is driven by chronic lung disease (COPD affects ~7.5% of Australian adults), obstructive sleep apnoea (prevalence ~10–15%), cigarette smoking, exogenous testosterone use, and high-altitude residence.
The Australian Institute of Health and Welfare (AIHW) data indicate that myeloproliferative neoplasms account for approximately 1,500–2,000 new registrations annually, with PV comprising a significant proportion. Notably, Aboriginal and Torres Strait Islander Australians have higher rates of smoking-related and chronic lung disease-associated secondary erythrocytosis, while access to haematology specialist services remains limited in remote and very remote areas of the Northern Territory, Western Australia, and Queensland.
Clinical pearl: An isolated elevated haemoglobin or haematocrit on a single FBC is insufficient for diagnosis. Pseudopolycythaemia (stress erythrocytosis / Gaisböck syndrome) — where plasma volume is reduced but red cell mass is normal — must be distinguished from true erythrocytosis by repeat testing and, where uncertain, red cell mass studies.
Confirm True Elevation
An elevated haemoglobin or haematocrit on a routine full blood count (FBC) is a common incidental finding. Before initiating an extensive workup, it is essential to confirm true erythrocytosis and exclude pre-analytical and physiological confounders.
Sex-Specific Diagnostic Thresholds
The 2016 World Health Organization (WHO) diagnostic criteria for polycythaemia vera incorporate the following haemoglobin and haematocrit thresholds, which should be applied when evaluating any patient with suspected erythrocytosis:
| Parameter | Men | Women |
|---|---|---|
| Haemoglobin (WHO 2016 PV criterion) | >165 g/L (>16.5 g/dL) | >160 g/L (>16.0 g/dL) |
| Haemoglobin (alternative PV criterion) | >170 g/L (>17.0 g/dL) | >150 g/L (>15.0 g/dL) |
| Haematocrit (high threshold) | >0.54 (54%) | >0.47 (47%) |
| Elevated red cell mass (RCM) by Cr-51 study | >36 mL/kg | >32 mL/kg |
Steps to Confirm True Erythrocytosis
1
Repeat FBC
Obtain a second FBC within 1–2 weeks under standardised conditions (patient seated for ≥5 minutes, non-fasting). Dehydration, stress, and venous stasis during collection can transiently elevate haemoglobin and haematocrit.
2
Assess Hydration Status
Correct dehydration and repeat. Consider concurrent urea, creatinine, and electrolytes to assess volume status. Pseudopolycythaemia secondary to dehydration is common in elderly patients and those on diuretics.
3
Consider Red Cell Mass Study
If the repeat FBC confirms erythrocytosis but clinical suspicion of pseudopolycythaemia remains, a chromium-51 red cell mass (RCM) study can distinguish true erythrocytosis from relative (apparent) polycythaemia. Available at select major tertiary centres (e.g. Royal Melbourne Hospital, Westmead Hospital). Not routinely required if the cause is clinically apparent.
4
Evaluate Spurious Results
Be aware that automated haematology analysers calculate haematocrit from red cell count and mean corpuscular volume (MCV); high MCV may overestimate Hct. In patients with concurrent folate or B12 deficiency, MCV may mask true erythrocytosis.
Urgent presentation: If the patient presents with symptoms of hyperviscosity (severe headache, blurred vision, focal neurological deficit, priapism) or acute thrombosis (stroke, DVT, PE, Budd-Chiari syndrome) alongside markedly elevated Hct (>0.55), initiate urgent haematology referral and consider emergency venesection while the workup proceeds.
Initial Workup
Once true erythrocytosis is confirmed, a systematic initial evaluation is required to identify potentially reversible secondary causes before considering a primary myeloproliferative neoplasm.
History — Key Areas to Explore
- Smoking history: Pack-years, current status. Chronic carbon monoxide exposure from smoking causes a compensatory erythrocytosis (carboxyhaemoglobin levels of 5–15% in active smokers).
- Obstructive sleep apnoea (OSA): Snoring, witnessed apnoeas, excessive daytime somnolence, Epworth Sleepiness Scale score ≥10. Nocturnal hypoxaemia drives erythropoietin production.
- Chronic lung disease: COPD, pulmonary fibrosis, bronchiectasis — all common in Australia, particularly in ex-smokers and Aboriginal communities. Resting oxygen saturation <92% is a red flag.
- Altitude: Residence or prolonged stay at altitude (>2,000 m). Notable for Australians who have lived in highland regions of Papua New Guinea, Andean countries, or the Ethiopian highlands.
- Exogenous testosterone / androgen use: Testosterone replacement therapy (TRT) for hypogonadism is increasingly prescribed in Australia. Erythrocytosis occurs in 5–20% of men on TRT and is the most common adverse effect requiring dose modification. Also consider anabolic-androgenic steroid (AAS) use in athletes or bodybuilders.
- Performance-enhancing substances: Recombinant erythropoietin (EPO) or darbepoetin misuse in athletes (cycling, endurance sports); blood doping.
- Renal disease: Autosomal dominant polycystic kidney disease (ADPKD), renal cell carcinoma, post-renal transplant erythrocytosis (occurs in ~10–15% of renal transplant recipients).
- High-altitude occupation: Aviation (unpressurised aircraft), mining in elevated regions.
- Cardiac disease: Right-to-left cardiac shunts (Eisenmenger syndrome, cyanotic congenital heart disease).
- Family history: Hereditary erythrocytosis (e.g. high-oxygen-affinity haemoglobin variants, VHL mutations, EGLN1/PHD2 mutations, EPOR mutations) — rare but important to consider in younger patients.
- Thrombotic history: Prior DVT, PE, stroke, TIA, splanchnic vein thrombosis (portal vein, hepatic vein, mesenteric vein) — splanchnic vein thrombosis may be the presenting feature of occult PV.
- Symptoms suggestive of PV: Aquagenic pruritus (itching after hot shower/bath — pathognomonic, occurs in ~40% of PV), erythromelalgia (burning pain and erythema of extremities), early satiety (splenomegaly), gout, peptic ulcer disease.
Physical Examination
- Ruddy plethora: Plethoric facies, injected conjunctivae, redness of palms and mucous membranes due to expanded red cell mass.
- Splenomegaly: Present in ~75% of PV at diagnosis; palpable spleen below the left costal margin is a key finding. Also assess for hepatomegaly (~30% of PV).
- Oxygen saturation: Pulse oximetry (SpO₂) at rest and during exertion. SpO₂ <92% at rest suggests significant cardiopulmonary disease; consider arterial blood gas (ABG) if SpO₂ borderline.
- BMI and neck circumference: Obesity (BMI >30) and neck circumference >43 cm in men (>41 cm in women) increase OSA risk.
- Signs of chronic lung disease: Barrel chest, wheeze, reduced air entry, clubbing.
- Cardiovascular examination: Murmurs (right-to-left shunt), elevated JVP, peripheral oedema.
- Skin: Erythromelalgia (erythema, warmth, pain in digits), excoriations from pruritus, ecchymoses (if concurrent thrombocytosis with aspirin use).
- Neurological examination: Focal deficits suggestive of prior thrombotic stroke; visual field assessment.
Initial Laboratory Investigations
Essential
Full Blood Count (FBC) with differential
Confirms erythrocytosis; assess platelet count (may be elevated in PV), WCC (may be elevated in PV). Repeat on two occasions.
Essential
Peripheral blood film
Assess for leucoerythroblastic features, tear-drop cells, giant platelets; may suggest myelofibrosis or marrow infiltration.
Essential
Iron studies (ferritin, transferrin saturation)
Iron deficiency may mask true Hb elevation (microcytic erythrocytosis); also assess for concurrent iron deficiency from occult GI blood loss.
Essential
Serum erythropoietin (EPO) level
Pivotal discriminator: low/inappropriately normal EPO suggests PV; elevated EPO suggests secondary cause. Available on Medicare (MBS item 66709).
Essential
JAK2 V617F mutation (molecular)
Screen in all patients with suspected primary erythrocytosis. Sensitivity ~95–97% for PV. Available at major Australian pathology laboratories (Sullivan Nicolaides, Douglass Hanly Moir, Melbourne Pathology). MBS-funded when criteria met.
Available
JAK2 exon 12 mutation analysis
Order if JAK2 V617F negative but PV still clinically suspected (~3% of PV carry exon 12 mutations). Available at reference laboratories (e.g. SA Pathology, PathWest).
Essential
Pulse oximetry / arterial blood gas
Screen for hypoxaemic secondary erythrocytosis. ABG provides PaO₂ and carboxyhaemoglobin (COHb) — elevated COHb confirms smoking-related erythrocytosis.
Available
Urea, creatinine, electrolytes; LFTs
Renal impairment and hepatocellular carcinoma should be excluded as secondary causes.
Available
Uric acid
Often elevated in PV due to increased cell turnover; may identify concurrent gout.
Available
B12 and folate levels
Elevated B12 may suggest hepatic disease or myeloproliferative neoplasm; folate/B12 deficiency may mask erythrocytosis via macrocytosis.
Available
Coagulation studies (INR, APTT, fibrinogen)
Acquired von Willebrand disease may occur with extreme thrombocytosis; baseline coagulation before initiating aspirin.
Referral
Chest X-ray / CT chest
Assess for COPD, pulmonary fibrosis, mass lesions (renal cell carcinoma, hepatocellular carcinoma, cerebellar haemangioblastoma — VHL syndrome).
Referral
Polysomnography (sleep study)
If clinical features of OSA present — readily accessible through public and private sleep medicine services across Australia.
Specialist
Bone marrow biopsy with cytogenetics
WHO 2016 major criterion for PV diagnosis. Shows hypercellularity for age with trilineage growth (panmyelosis). Performed by haematologist. Also provides karyotype and BCR-ABL1 to exclude CML.
Specialist
Red cell mass (Cr-51) study
Gold standard for confirming true vs apparent erythrocytosis when diagnosis uncertain. Available at limited tertiary centres.
Differentiating Primary vs Secondary Erythrocytosis
The distinction between primary (clonal) and secondary (reactive) erythrocytosis is the central diagnostic challenge. Serum erythropoietin (EPO) level is the single most informative initial test after true erythrocytosis is confirmed.
Diagnostic Algorithm
Key discriminator — Serum Erythropoietin: In the setting of confirmed erythrocytosis, a low or inappropriately normal EPO level has a high positive predictive value for polycythaemia vera. An elevated EPO level indicates a secondary cause or, rarely, a familial erythrocytosis due to an EPO receptor mutation (where EPO may be low/normal despite elevated EPO sensitivity).
| Feature | Primary (Polycythaemia Vera) | Secondary Erythrocytosis |
|---|---|---|
| Serum EPO | Low or inappropriately normal | Elevated (physiological response) |
| JAK2 V617F / exon 12 | Positive (~98% of PV) | Negative |
| Splenomegaly | Common (~75%) | Uncommon (unless hepatorenal cause) |
| Leucocytosis / thrombocytosis | Often present (panmyelosis) | Typically absent |
| Pruritus (aquagenic) | Characteristic (~40%) | Absent |
| Bone marrow biopsy | Panmyelosis, pleomorphic megakaryocytes | Normal or erythroid-predominant |
| SpO₂ / PaO₂ | Normal (unless concurrent lung disease) | Often reduced (hypoxic cause) |
| Common aetiologies | Clonal JAK2-mutant stem cell disorder | COPD, OSA, smoking, testosterone, altitude, renal disease, EPO-secreting tumour |
Secondary Causes — Comprehensive Screening
Hypoxia-Driven
- COPD / chronic bronchiectasis
- Obstructive sleep apnoea
- Obesity hypoventilation syndrome (BMI >30)
- High altitude residence (>2,000 m)
- Right-to-left cardiac shunt (cyanotic CHD, Eisenmenger)
- Chronic carbon monoxide exposure (smoking, occupational)
- Hypoventilation syndromes (neuromuscular, chest wall)
Non-Hypoxia-Driven
- Exogenous testosterone / androgen therapy
- Exogenous EPO / darbepoetin (sport doping, CKD treatment)
- Renal: ADPKD, renal artery stenosis, post-renal transplant
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cerebellar haemangioblastoma (VHL syndrome)
- Uterine leiomyoma (rare)
- Hereditary: high-affinity Hb variants, VHL/EGLN1/EPOR mutations
- Meningioma, phaeochromocytoma, paraganglioma (rare)
Splanchnic vein thrombosis alert: Budd-Chiari syndrome (hepatic vein thrombosis) and portal vein thrombosis may be the presenting manifestation of occult PV. In any patient with unexplained splanchnic vein thrombosis, test for JAK2 V617F — even if haemoglobin is normal, as concurrent iron deficiency or hepatocellular disease may mask erythrocytosis.
WHO 2016 Diagnostic Criteria for Polycythaemia Vera
PV is diagnosed when all three major criteria are met, or when the first two major criteria plus the minor criterion are fulfilled:
| Criterion | Type | Detail |
|---|---|---|
| Major 1 | Haemoglobin / Haematocrit | Hb >165 g/L (men) / >160 g/L (women); or Hct >0.49 (men) / >0.48 (women); or elevated red cell mass (>25% above predicted) |
| Major 2 | Bone marrow biopsy | Hypercellularity for age with trilineage growth (panmyelosis) including pleomorphic, mature megakaryocytes |
| Major 3 | Molecular | JAK2 V617F or JAK2 exon 12 mutation |
| Minor | Biochemical | Subnormal serum erythropoietin level |
Risk Stratification & Thrombotic Risk Assessment
Thrombotic events are the leading cause of morbidity and mortality in polycythaemia vera. Risk stratification determines the intensity of therapy and guides decisions regarding venesection alone versus addition of cytoreductive agents.
Low Risk
PV — Low Thrombotic Risk
Age <60 years AND no prior thrombosis. JAK2 V617F positive but meeting low-risk criteria.
Management: Low-dose aspirin + venesection to target Hct <0.45. Monitor FBC every 1–3 months initially, then every 3–6 months.
High Risk
PV — High Thrombotic Risk
Age ≥60 years OR prior thrombotic event (arterial or venous). Includes patients with splanchnic vein thrombosis as presenting feature.
Management: Low-dose aspirin + venesection (Hct <0.45) + cytoreductive therapy (first-line: hydroxycarbamide). Consider ruxolitinib if hydroxycarbamide intolerant/resistant.
Very High Risk
Extreme Thrombocytosis or Hyperviscosity
Platelet count >1,500 × 10⁹/L (risk of acquired von Willebrand disease); Hct >0.55 (markedly increased viscosity); symptoms of hyperviscosity; progressive splenomegaly; constitutional symptoms (fever, night sweats, weight loss).
Urgent haematology referral. Emergency venesection if hyperviscosity symptoms. Cytoreduction with hydroxycarbamide ± ruxolitinib. Consider pegylated interferon in younger patients.
Additional Thrombotic Risk Factors in PV
- JAK2 V617F allele burden — higher burden associated with increased thrombotic risk
- Cardiovascular risk factors: hypertension, diabetes mellitus, hyperlipidaemia, obesity, smoking
- Concurrent thrombocytosis (>400 × 10⁹/L) or leucocytosis (>11 × 10⁹/L)
- Prior venous thromboembolism (especially splanchnic, cerebral)
- Female sex (higher risk of splanchnic vein thrombosis, particularly with oral contraceptive use)
Management of Polycythaemia Vera
Management of PV is tailored to thrombotic risk category. All patients with PV require treatment aimed at maintaining haematocrit below 0.45, as demonstrated by the CYTO-PV trial (Marchioli et al., NEJM 2013).
First-Line Therapy: Venesection + Low-Dose Aspirin
CYTO-PV Trial (NEJM 2013): Maintaining haematocrit <0.45 (stricter target) vs <0.50 (less strict) in PV patients reduced the composite endpoint of cardiovascular death and major thrombotic events by approximately 4-fold (HR 4.31 for less strict target). This is the standard of care in Australia.
Venesection (Therapeutic Phlebotomy)
- Target: Haematocrit <0.45 (all risk groups)
- Volume: 250–500 mL per session (one unit of whole blood equivalent)
- Frequency: Initially every 1–2 weeks until target Hct achieved; then every 4–12 weeks for maintenance (individually tailored based on rate of Hct rise)
- Setting: Performed at hospital day centres, Australian Red Cross Lifeblood donor centres (in some states, by arrangement), or haematology outpatient clinics
- Iron monitoring: Serial venesection depletes iron stores — ferritin will fall. Do not supplement iron unless symptomatic anaemia develops, as iron repletion may accelerate erythropoiesis and counteract venesection benefit
- MBS item: Therapeutic venesection is claimable under MBS items when performed for diagnosed PV (haematology outpatient attendance item also applicable)
Aspirin (low-dose)
Cartia® · Astrix® · Generic · Antiplatelet
Adult dose
75–100 mg PO once daily
Paediatric dose
Not routinely indicated in paediatric PV (specialist guidance required)
Renal adjustment
No dose adjustment; use with caution if eGFR <30 mL/min (bleeding risk)
Hepatic adjustment
Avoid in severe hepatic impairment (coagulopathy risk)
PBS status
✔ PBS General Benefit
Notes
Contraindicated if platelet count >1,500 × 10⁹/L (acquired von Willebrand disease risk — assess with ristocetin cofactor assay first). Reduces thrombotic events in low-risk PV by ~60% (ECLAP trial).
Cytoreductive Therapy (High-Risk PV)
Cytoreductive agents are indicated for high-risk and very-high-risk PV patients, or those who cannot achieve Hct <0.45 with venesection alone (e.g. intolerance, high venesection frequency requirement, symptomatic splenomegaly, progressive thrombocytosis).
Hydroxycarbamide (Hydroxyurea)
Hydrea® · Generic · Antimetabolite / Cytoreductive
Adult dose
500–1,000 mg PO once daily, titrated to maintain Hct <0.45, platelet count <400 × 10⁹/L, WCC <10 × 10⁹/L
Paediatric dose
20–30 mg/kg/day PO (specialist supervision only)
Renal adjustment
Reduce dose if eGFR <30 mL/min; monitor FBC more frequently
Hepatic adjustment
No specific recommendation; monitor closely
PBS status
✔ PBS Authority Required
Monitoring
FBC every 2–4 weeks during titration, then every 1–3 months. Monitor renal function and LFTs. Monitor skin for non-melanoma skin cancer (chronic use risk).
Key cautions
Teratogenic — effective contraception required in women of childbearing potential. May increase leukaemia transformation risk (debated in PV). Avoid in young patients (<40) if possible — consider pegylated interferon.
Ruxolitinib
Jakafi® / Jakavi® · JAK1/JAK2 Inhibitor
Adult dose
10–25 mg PO BD, based on platelet count. Starting dose: 10 mg BD if platelets 100–125 × 10⁹/L; 15 mg BD if 125–175 × 10⁹/L; 20 mg BD if 175–400 × 10⁹/L; 25 mg BD if >400 × 10⁹/L
Indication
PV patients intolerant of or resistant to hydroxycarbamide. TGA/PBS approved for this indication.
Renal adjustment
eGFR 15–29: reduce to 10 mg BD initially. eGFR <15 or dialysis: avoid or use with extreme caution.
Hepatic adjustment
Child-Pugh A: no adjustment. Child-Pugh B/C: reduce dose by ~50%; avoid if possible.
PBS status
✔ PBS Authority Required (Specialist only)
Monitoring
FBC every 2–4 weeks for first 3 months, then as clinically indicated. Monitor for herpes zoster reactivation (consider antiviral prophylaxis). Screen for infections including tuberculosis before initiation.
Pegylated Interferon Alfa-2a
Pegasys® · Cytokine / Immunomodulator
Adult dose
45–90 µg SC once weekly (or PEG-IFN alfa-2b 50 µg SC weekly), titrated to response over 3–6 months
Indication
Second-line or preferred cytoreductive in younger patients (<40–50 years) due to potential for molecular remission (JAK2 allele burden reduction) and absence of leukaemogenic risk. Also used in pregnancy (under specialist guidance).
Renal adjustment
No specific adjustment; use with caution if eGFR <30
Hepatic adjustment
Contraindicated in decompensated hepatic disease
PBS status
✔ PBS Authority Required (Specialist only)
Key side effects
Flu-like symptoms, fatigue, depression, cytopenias, autoimmune thyroiditis, hepatotoxicity. Pre-medication with paracetamol 1 g PO recommended.
Management of Secondary Erythrocytosis
Treatment of secondary erythrocytosis is directed at the underlying cause. Venesection is not routinely recommended for secondary erythrocytosis unless haematocrit exceeds 0.56 and there are symptoms attributable to hyperviscosity, as aggressive venesection may worsen tissue oxygen delivery in hypoxic patients.
- Smoking-related: Smoking cessation counselling and support (Quitline 13 7848, nicotine replacement therapy or varenicline)
- OSA: CPAP therapy, weight management, sleep physician referral
- COPD: Optimise bronchodilator therapy, long-term oxygen therapy (LTOT) if criteria met (PaO₂ ≤55 mmHg or ≤59 mmHg with cor pulmonale), pulmonary rehabilitation
- Testosterone / androgen therapy: Dose reduction, increased monitoring frequency, consider discontinuation if Hct rises above 0.54. TGA recommends regular FBC monitoring in all men on TRT.
- High-altitude: Acclimatisation advice; relocation if medically indicated
- Renal / endocrine causes: Nephrology / endocrine referral; management of underlying renal tumour or ADPKD
Monitoring
Long-term monitoring of PV and erythrocytosis requires regular assessment of haematological parameters, thrombotic risk, treatment side effects, and disease progression. The following framework applies to managed patients with confirmed PV:
| Parameter | Frequency | Target / Notes |
|---|---|---|
| FBC (Hct, Hb, WCC, platelets) | Every 1–3 months (stable); every 2–4 weeks (titration phase) | Hct <0.45; platelets <400 × 10⁹/L; WCC <10 × 10⁹/L |
| Serum ferritin | Every 3–6 months | Declining levels expected with serial venesection; avoid supplementation unless symptomatic iron deficiency |
| Uric acid | Every 6–12 months | Monitor for hyperuricaemia / gout (increased cell turnover); treat with allopurinol if recurrent |
| Renal function (eGFR) | Every 6–12 months | Required for medication dosing adjustments |
| LFTs | Every 6–12 months | Hepatomegaly, Budd-Chiari surveillance, hepatotoxicity from cytoreductives |
| JAK2 V617F allele burden | Every 6–12 months (specialist setting) | Declining burden suggests treatment response; molecular remission possible with interferon |
| Skin examination | Annually (more frequently on hydroxycarbamide) | Hydroxycarbamide increases non-melanoma skin cancer risk |
| Cardiovascular risk factors | Every 3–6 months | BP, lipids, HbA1c, smoking status, BMI — aggressive CV risk management is essential |
| Spleen size (clinical ± ultrasound) | Every 6–12 months | Progressive splenomegaly may indicate disease progression or myelofibrotic transformation |
| Bone marrow biopsy | If disease progression suspected (progressive fibrosis, resistance to therapy) | Assess for transformation to myelofibrosis (~10–20% over 15–20 years) or acute myeloid leukaemia (~1–3%) |
Iron deficiency monitoring: Serial venesection will inevitably deplete iron stores. Iron-deficient patients may develop microcytosis, fatigue, restless legs syndrome, and pica. However, do not supplement iron in PV patients unless symptomatic iron deficiency is severe (ferritin <15 µg/L with transferrin saturation <10%) and haematocrit remains controlled, as iron repletion stimulates erythropoiesis and may worsen erythrocytosis.
Special Populations
Pregnancy
Hydroxycarbamide
Teratogenic — must be ceased at least 3–6 months before conception. Category D (TGA). Effective contraception required during treatment and for 6 months after last dose.
Ruxolitinib
Category D — teratogenic in animal studies. Discontinue before conception. Insufficient human data in pregnancy.
Pegylated interferon alfa-2a
Category B3 — only cytoreductive agent considered relatively safe in pregnancy for PV when required. Specialist supervision essential. Can be continued through pregnancy in high-risk PV if benefits outweigh risks.
Aspirin
Low-dose aspirin (100 mg/day) can generally be continued in pregnancy for PV. Also has benefit in preventing pre-eclampsia. Discuss with haematologist and obstetrician.
Venesection
Can be continued during pregnancy with close monitoring. Frequency may need adjustment. Haematocrit target remains <0.45. Coordinate with obstetric haematology.
General: PV in pregnancy increases risk of miscarriage (up to 25–30%), pre-eclampsia, fetal growth restriction, and maternal thrombosis. All pregnant PV patients should be managed jointly by haematology and high-risk obstetrics. Antenatal thromboprophylaxis with LMWH should be considered.
Paediatric
PV in children
Extremely rare in paediatric populations. Diagnostic criteria adapted from adult WHO criteria. JAK2 V617F positive in ~50–70% of childhood PV (lower than adults). Hereditary erythrocytosis is relatively more common in children — consider genetic testing (VHL, EGLN1, EPOR, HIF2A, high-affinity haemoglobin variants).
Management
Paediatric haematology referral mandatory. Venesection first-line where feasible. Hydroxycarbamide used under specialist guidance if cytoreduction needed. Aspirin use in children requires careful risk-benefit assessment.
Key point: Always exclude congenital cyanotic heart disease and hereditary causes before considering a myeloproliferative neoplasm in a child.
Elderly (≥65 years)
Increased thrombotic risk
Age ≥60 is itself a major risk factor for thrombosis in PV. Aggressive Hct control (<0.45) and cytoreduction are indicated. Higher prevalence of comorbidities (AF, diabetes, CKD) complicates management.
Hydroxycarbamide
First-line cytoreductive agent in the elderly. More frequent monitoring for myelosuppression. Renal function often reduced — start at lower dose (500 mg/day). Skin cancer surveillance important.
Venesection tolerance
Elderly patients may poorly tolerate large-volume or frequent venesection due to cardiovascular comorbidities, anaemia risk, and iron depletion. Consider smaller volume (250 mL) venesections and earlier transition to cytoreductive therapy.
Monitoring: Falls risk assessment (aspirin-related bleeding), anticoagulant interactions (AF + aspirin), polypharmacy review, bone health assessment.
Renal Impairment
Renal erythrocytosis
ADPKD, renal artery stenosis, and post-renal transplant erythrocytosis (occurs in ~10–15% of transplant recipients) are important secondary causes. ACE inhibitors (e.g. enalapril) or ARBs (e.g. losartan) are effective in treating post-transplant erythrocytosis.
Hydroxycarbamide
Reduce dose if eGFR <30 mL/min. Increase FBC monitoring frequency. Active metabolites renally cleared.
Ruxolitinib
eGFR 15–29: start at 10 mg BD. eGFR <15: avoid or use with extreme caution under specialist guidance.
Key point: Always exclude renal cell carcinoma and ADPKD as secondary causes of erythrocytosis — renal ultrasound or CT abdomen may be indicated.
Hepatic Impairment
Hepatocellular carcinoma (HCC)
EPO-secreting HCC should be considered in any patient with hepatic disease and unexplained erythrocytosis. AFP and hepatic imaging (ultrasound/CT) are warranted.
Budd-Chiari syndrome
Hepatic vein thrombosis is a classic presenting feature of occult PV. Test for JAK2 in all patients with unexplained hepatic vein or portal vein thrombosis.
Ruxolitinib
Child-Pugh A: no adjustment. Child-Pugh B: reduce dose. Child-Pugh C: avoid if possible.
Aspirin: Use with caution in patients with significant hepatic impairment (coagulopathy, varices, portal hypertensive gastropathy).
Immunocompromised
Ruxolitinib
JAK inhibition impairs immune function. Screen for latent TB (QuantiFERON-TB Gold) before initiation. Increased risk of herpes zoster recombination — consider antiviral prophylaxis (valaciclovir 500 mg PO daily). Risk of hepatitis B reactivation — screen HBsAg/anti-HBc before starting.
Pegylated interferon
May exacerbate autoimmune conditions. Monitor thyroid function (TSH, anti-TPO). Contraindicated in severe psychiatric illness. Screen for depression before and during treatment.
Hydroxycarbamide
Myelosuppressive — increases infection risk. Monitor FBC closely. Avoid live vaccines during treatment. Consider Pneumococcal and influenza vaccination.
When to Refer
Timely haematology referral is essential for appropriate diagnosis and management of polycythaemia vera and for evaluation of unexplained or refractory erythrocytosis. The following scenarios mandate specialist referral:
1
Confirmed JAK2-Positive Erythrocytosis
All patients with a positive JAK2 V617F or exon 12 mutation require haematology assessment for bone marrow biopsy (WHO diagnostic criteria), risk stratification, initiation of therapy, and long-term surveillance. Referral should be urgent if concurrent thrombosis or hyperviscosity symptoms are present.
2
High Haematocrit with Thrombosis Risk
Haematocrit persistently >0.50 in men or >0.48 in women, particularly with additional thrombotic risk factors (age ≥60, prior VTE, cardiovascular disease, thrombocytosis), warrants urgent haematology review. Do not delay referral while awaiting JAK2 results if Hct is markedly elevated.
3
Unexplained Erythrocytosis
Persistent true erythrocytosis after exclusion of common secondary causes (smoking, OSA, COPD, testosterone, altitude) and with a low or normal serum EPO level requires specialist evaluation for occult myeloproliferative neoplasm, rare hereditary causes, or EPO-secreting tumours.
4
Symptoms of Hyperviscosity or Splenomegaly
Severe headache, visual disturbance, tinnitus, digital ischaemia (erythromelalgia), priapism, or clinically significant splenomegaly in the context of erythrocytosis constitutes a medical emergency. Refer urgently (same-day or next-day) to haematology. Initiate emergency venesection if the patient is symptomatic with Hct >0.55 while awaiting specialist review.
5
Splanchnic Vein Thrombosis
Budd-Chiari syndrome, portal vein thrombosis, or mesenteric vein thrombosis — particularly in young women or in the absence of cirrhosis — should prompt JAK2 testing and urgent haematology referral, as these are presenting features of occult PV in ~20–40% of cases.
6
Refractory or Intolerant to First-Line Cytoreduction
Patients who cannot tolerate hydroxycarbamide, who have inadequate haematological response despite maximum dose, or who develop resistance (rising Hct/platelets/WCC despite therapy) require specialist review for second-line options including ruxolitinib or pegylated interferon.
Emergency referral criteria: Present to ED and contact on-call haematology for: (1) symptomatic hyperviscosity (severe headache, confusion, visual changes, focal neurological deficit); (2) acute thrombosis (stroke, PE, DVT, MI) with concurrent erythrocytosis; (3) Budd-Chiari syndrome; (4) Hct >0.60 — risk of spontaneous thrombosis is extreme. Initiate emergency venesection (remove 250–500 mL) and IV crystalloid resuscitation while awaiting haematology review.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
Aboriginal and Torres Strait Islander Australians experience a disproportionate burden of conditions causing secondary erythrocytosis, particularly chronic lung disease, smoking-related illness, and rheumatic heart disease with associated cyanotic cardiac complications. The intersection of these comorbidities with limited specialist access in remote communities creates a significant health equity challenge in the diagnosis and management of erythrocytosis.
Key Considerations
Recommended approach: Coordinate erythrocytosis workup through Aboriginal Community Controlled Health Organisations (ACCHOs) where possible. Utilise specialist outreach and telehealth services. Ensure JAK2 testing is ordered early when erythrocytosis is identified, to minimise diagnostic delays. Support remote health practitioners with clear referral pathways and decision support tools for erythrocytosis evaluation.
📚 References
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