Polycythaemia vera and MPNs: what your blood count is telling you

What are myeloproliferative neoplasms?

Myeloproliferative neoplasms (MPNs) are a group of bone marrow disorders in which stem cells produce too many of one or more types of blood cell. Unlike leukaemia, the overproduction is usually well-differentiated — the cells look mostly normal — but the sheer volume and functional abnormalities drive the major problems: blood clot formation, enlarged spleen, and over time, a small risk of transformation to acute leukaemia.

Approximately 14,000 Australians have an MPN, according to Leukaemia Foundation Australia. The three main Philadelphia-chromosome-negative MPNs are:

• Polycythaemia vera (PV, ICD-10 D45) — excess red cell production, elevated haemoglobin and haematocrit, driven by JAK2 V617F in ~95% of cases.
• Essential thrombocythaemia (ET, ICD-10 D47.3) — sustained platelet excess above 450 × 10⁹/L, driven by JAK2 V617F (~50%), CALR mutation (~25%), or MPL mutation (~5%).
• Primary myelofibrosis (PMF, ICD-10 D47.4) — progressive marrow fibrosis, splenomegaly, anaemia, and constitutional symptoms; the highest transformation risk of the three.

Chronic myeloid leukaemia (CML) is a separate entity driven by the BCR::ABL1 Philadelphia chromosome fusion, treated with tyrosine kinase inhibitors — it is not covered in depth here.

A. Core clinical — the AU general practice framework

Recognising an MPN from the FBC

The starting point for all MPNs is the full blood count (FBC) and blood film. Key patterns:

Polycythaemia vera: Haemoglobin consistently above 185 g/L in men or 165 g/L in women, raised haematocrit, and commonly elevated white cell count and platelet count (a “triple high” picture). The blood film typically shows red-cell overcrowding without abnormal forms. Aquagenic pruritus — an intense itch triggered by hot water bathing — is a highly characteristic symptom that should immediately prompt MPN consideration.

Essential thrombocythaemia: Sustained platelet count above 450 × 10⁹/L on at least two separate occasions, often discovered incidentally. The blood film should be reviewed to exclude reactive causes (such as iron deficiency, acute illness, or post-surgical thrombocytosis, which are far more common than ET). Reactive thrombocytosis rarely exceeds 1,000 × 10⁹/L and resolves with the trigger.

Myelofibrosis: Anaemia with a leucoerythroblastic blood film — nucleated red cells, immature granulocytes, and characteristic tear-drop-shaped red cells (dacryocytes). Massive splenomegaly producing abdominal fullness and early satiety. Constitutional symptoms including drenching night sweats, unintentional weight loss, and profound fatigue are common.

Initial GP investigations

The following investigations should be ordered before or at the same time as the haematology referral:

• FBC with differential and blood film — MBS item 65070. Request a film review with the clinical question stated.
• Serum erythropoietin (EPO) — the single most useful discriminator of PV from secondary erythrocytosis. EPO is low in PV; it is normal or high in secondary causes (lung disease, OSA, kidney tumour, exogenous EPO use).
• Ferritin and iron studies — PV is commonly iron-deficient after venesection, but also because iron deficiency is a differential for raised platelets (thrombocytosis).
• UEC, LFTs, LDH, uric acid — baseline and for staging.
• Abdominal ultrasound — MBS item 55054 — to assess spleen size, liver, and screen for RCC or HCC as secondary causes of erythrocytosis.
• JAK2 V617F molecular testing — ordered by specialist pathology or haematologist (rebatable through haematology pathway); CALR and MPL mutations are tested simultaneously for ET and MF workup.
• Bone marrow aspirate and trephine — specialist-led; required for WHO 2022 diagnostic criteria in most cases.

Key diagnostic pitfalls

• Never supplement iron in undiagnosed or confirmed PV. Iron deficiency is the deliberate effect of venesection. Iron supplementation drives the haematocrit upward, into the thrombosis danger zone.
• Apparent (spurious) erythrocytosis — in middle-aged, hypertensive, overweight, smoking men on diuretics — reflects plasma-volume contraction, not true excess red-cell mass. Hydrate and repeat.
• Do not send JAK2 testing before excluding reactive thrombocytosis (iron deficiency, infection, inflammation) — JAK2 should be a targeted test once reactive causes are unlikely.

B. Evidence appraisal

Haematocrit target in polycythaemia vera

The CYTO-PV trial (Marchioli et al., NEJM 2013) randomised 365 patients to haematocrit targets of either below 45% or 45–50%. The group maintained below 45% had a rate of major cardiovascular events (death or thrombosis) of 1.1 per 100 patient-years compared with 4.4 per 100 patient-years in the higher group — a hazard ratio of 3.91 (p=0.007). The target of haematocrit below 45% is now universally adopted by the BSH, NCCN, and European LeukemiaNet.

Aspirin in PV

The ECLAP trial (Landolfi et al., NEJM 2004) randomised 518 patients with PV to aspirin 100 mg daily versus placebo. The combined endpoint of non-fatal myocardial infarction, non-fatal stroke, PE, major venous thrombosis, or death from cardiovascular cause was reduced by aspirin (relative risk 0.40; 95% CI 0.18–0.91). Low-dose aspirin is now standard for all PV patients unless contraindicated. The one exception: platelets above 1,500 × 10⁹/L are associated with acquired von Willebrand disease and bleeding risk; aspirin should be withheld until cytoreduction brings platelets down.

Ruxolitinib for HU-resistant PV

The RESPONSE trial (Vannucchi et al., NEJM 2015) demonstrated that ruxolitinib achieved the composite primary endpoint (haematocrit control plus spleen-volume reduction) in 21% of patients versus 1% in the best-available-therapy arm (p < 0.001) in HU-intolerant or HU-resistant PV. Ruxolitinib (Jakavi) is listed on the PBS as a Section 100 Highly Specialised Drug for this indication.

Ruxolitinib and momelotinib in myelofibrosis

The COMFORT-I trial (Verstovsek et al., NEJM 2012) established ruxolitinib as the standard of care for symptomatic intermediate-2 or high-risk myelofibrosis — achieving ≥35% spleen-volume reduction in 41.9% of patients versus 0.7% with placebo, and significant improvements in constitutional symptoms.

For the growing subgroup of myelofibrosis patients with anaemia (haemoglobin below 100 g/L), the MOMENTUM trial (Verstovsek et al., Lancet 2023) showed momelotinib (Omjjara) was superior to danazol for symptom response, splenic response, and transfusion independence. Momelotinib was listed on the PBS in 2024 for this anaemic phenotype.

C. Australian operations

MBS items

• GP standard consults: items 23 / 36 / 44.
• FBC plus blood film: item 65070.
• Abdominal ultrasound: item 55054.
• Therapeutic venesection: items 13757 and 13754. GPs with appropriate facilities can perform venesection in-rooms; alternatively, Lifeblood (Australian Red Cross) operates a therapeutic venesection service for medically referred patients.
• GPCCMP (replaces GPMP/TCA from 1 July 2025): items 965 and 967 — MPN qualifies as a chronic condition.
• MHCP: items 2715 and 2717 — for transformation-related anxiety, fertility distress, and financial toxicity.
• ATSI Health Assessment: item 715.

PBS medications

• Hydroxyurea (Hydrea) — PBS Authority Required Streamlined for high-risk PV and ET.
• Anagrelide (Agrylin) — PBS Authority Streamlined, second-line for ET.
• Ruxolitinib (Jakavi) — PBS Authority Required Section 100 HSD for myelofibrosis (intermediate-2/high-risk, symptomatic) and HU-intolerant/resistant PV.
• Momelotinib (Omjjara) — PBS Authority Required Section 100, listed 2024 for anaemic-phenotype myelofibrosis (haemoglobin below 100 g/L).
• Fedratinib (Inrebic) — PBS Section 100 for second-line myelofibrosis.
• Aspirin — general schedule / over-the-counter.
• Ropeginterferon-α-2b (Besremi) — TGA-registered for PV but not currently PBS-listed; available on compassionate/private supply or through clinical trials.

Vaccinations in MPN

Patients on JAK inhibitors (ruxolitinib, momelotinib, fedratinib) are immunocompromised. Per ATAGI’s Australian Immunisation Handbook, they need:

• Annual influenza vaccine (NIP-funded).
• Pneumococcal vaccine (13-valent + 23-valent schedule).
• Shingrix (recombinant zoster vaccine — non-live) — complete the 2-dose course before starting a JAK inhibitor where possible.
• COVID-19 boosters per current ATAGI recommendations.
• Live vaccines are contraindicated while on JAK inhibitors or high-dose systemic immunosuppression — MMR, varicella, live zoster, and BCG must not be given.

D. Special populations

Pregnancy in PV and ET

Pregnancy in women with PV or ET carries high risks: miscarriage, placental thrombosis, foetal growth restriction, preterm delivery, and maternal thrombotic or haemorrhagic complications. Management requires shared care between haematology and obstetrics.

Key points:

• Hydroxyurea is teratogenic — must be stopped well before conception and strict contraception used while taking it.
• JAK inhibitors are not recommended in pregnancy.
• Peg-interferon-α is the preferred cytoreductive agent for women who need treatment during pregnancy.
• Low-dose aspirin throughout pregnancy plus low-molecular-weight heparin prophylaxis throughout pregnancy and for 6 weeks postpartum in high-risk patients.
• Refer to a haematologist with MPN and obstetric experience before any planned pregnancy.

Adolescents and young adults with ET

Young women are over-represented in ET, often with a CALR mutation. The Budd-Chiari syndrome or splanchnic vein thrombosis may be the sentinel event — a young woman with unexplained hepatic vein thrombosis should have JAK2 V617F tested urgently. Fertility counselling and treatment planning with a haematologist experienced in MPN and pregnancy are essential.

Cardiovascular risk amplification

Every cardiovascular risk factor — hypertension, hyperlipidaemia, smoking, obesity, diabetes, sedentary lifestyle — amplifies MPN-related thrombosis risk multiplicatively, not additively. Aggressive management of all CV risk factors is as important as haematocrit control in PV. Smoking cessation is particularly critical.

When to escalate

Same-day (emergency referral or ambulance):

• Suspected acute thrombosis — stroke, TIA, MI, PE, DVT, or thrombosis at an unusual site (Budd-Chiari, portal, mesenteric, cerebral venous sinus) with known or suspected MPN.
• Haematocrit above 55% with neurological or cardiovascular symptoms — urgent venesection plus haematology.
• Circulating blasts or new pancytopenia — suspected transformation to AML.
• Fever and sepsis in a patient on JAK inhibitor — immunosuppression.

Urgent referral (within 1 week):

• Newly detected MPN-pattern FBC — haematology for bone marrow workup and molecular testing.
• Rapidly enlarging spleen with B-symptoms.
• Platelet count above 1,500 × 10⁹/L with bleeding.

Routine haematology follow-up: Stable PV on venesection and aspirin — 3-monthly GP review with FBC and blood pressure, annual haematology review.

What this article is and is not

This article is designed to help Australian patients understand myeloproliferative neoplasms in an accessible way. It is not a substitute for the individualised assessments, molecular testing, bone marrow examination, and treatment planning provided by a haematologist. MPN management is complex and evolves with new evidence and PBS listings. Please consult your haematologist and GP for advice that is specific to your diagnosis and circumstances.

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Sources cited

• CYTO-PV — Marchioli et al., NEJM 2013
• ECLAP — Landolfi et al., NEJM 2004
• RESPONSE — Vannucchi et al., NEJM 2015
• COMFORT-I — Verstovsek et al., NEJM 2012
• MOMENTUM — Verstovsek et al., Lancet 2023
• BSH Guidelines — PV, ET, PMF (McMullin 2024 update)
• Therapeutic Guidelines (eTG) — Haematological malignancies
• Leukaemia Foundation Australia — MPN
• MPN Australia
• AIHW — Cancer Data in Australia 2024
• ATAGI — Vaccination for immunocompromised people 2024
• Lifeblood — Therapeutic Venesection