About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Myeloproliferative neoplasm with JAK2 V617F mutation in >95% of cases — this is essentially the diagnostic test
- Raised haematocrit (Hct >0.52 in males, >0.48 in females), often with raised WCC and platelets (panmyelosis)
- Major risk is THROMBOSIS (arterial and venous) — Budd-Chiari syndrome (hepatic vein thrombosis) is a classic association
- First-line treatment: venesection to target Hct <0.45 + low-dose aspirin 75 mg daily
- High-risk patients (>60 years or prior thrombosis): add hydroxycarbamide (cytoreductive therapy)
Overview
Polycythaemia vera (PV) is a clonal myeloproliferative neoplasm characterised by uncontrolled proliferation of red blood cells, often accompanied by raised white cells and platelets (panmyelosis). The JAK2 V617F mutation (or rarely JAK2 exon 12 mutation) is the driver — present in >95% of PV cases. The mutation leads to constitutive activation of the JAK-STAT signalling pathway, making erythroid precursors hypersensitive to erythropoietin. The major clinical consequence is hyperviscosity and thrombotic risk.
Epidemiology
PV has an incidence of approximately 2-3 per 100,000 per year. The median age at diagnosis is 60-65 years, though it can occur at any adult age. Males are slightly more commonly affected. PV may transform to myelofibrosis (post-PV MF, ~10-20% at 20 years) or rarely to AML (~5% at 20 years). Life expectancy is near-normal with appropriate treatment and monitoring.
Clinical Features
Symptoms
Headache, dizziness, visual disturbance (hyperviscosity)
Pruritus — especially aquagenic pruritus (itching after hot bath/shower) — very characteristic
Facial plethora (ruddy complexion)
Fatigue
Erythromelalgia — burning pain and redness in hands and feet (microvascular thrombosis)
Gout (hyperuricaemia from high cell turnover)
Thrombosis — DVT, PE, stroke, MI, or unusual site thrombosis (portal, hepatic, mesenteric veins)
Signs
Facial plethora (congested red face)
Splenomegaly (70% at diagnosis)
Hepatomegaly
Hypertension
Conjunctival suffusion (engorged red conjunctival vessels)
Investigations
First-line
FBCRaised haematocrit (Hct >0.52 males, >0.48 females), raised Hb. Often raised WCC and platelets (panmyelosis)
JAK2 V617F mutationPOSITIVE in >95% of PV — this is the key diagnostic test. If negative, check JAK2 exon 12 mutation
Serum erythropoietin (EPO)LOW or undetectable in PV (suppressed by autonomous RBC production). This distinguishes PV from secondary polycythaemia where EPO is raised
Second-line
FerritinOften low (iron consumed by erythropoiesis, especially after venesection)
UrateRaised (high cell turnover)
LDHMildly raised
Specialist
Bone marrow biopsyPanmyelosis (trilineage hypercellularity) — not always required if JAK2 positive with classic presentation. Useful to assess fibrosis grade
Abdominal ultrasoundSplenomegaly assessment; hepatic/portal vein thrombosis screening (Budd-Chiari)
1
All patients
- Venesection: target Hct <0.45 (reduces thrombotic risk). Initially 1-2 sessions per week (450 mL each), then as needed
- Low-dose aspirin 75 mg daily (unless contraindicated) — reduces thrombotic events
- Cardiovascular risk factor management: smoking cessation, BP control, lipid management
2
High-risk patients (age >60 OR prior thrombosis)
- Add hydroxycarbamide (cytoreductive) — first-line cytoreductive agent
- Starting dose typically 500 mg BD, titrate to maintain Hct <0.45 and normalise counts
- Alternatives: interferon-alpha (preferred in younger patients and pregnancy), ruxolitinib (JAK inhibitor — for hydroxycarbamide-resistant/intolerant PV)
3
Low-risk patients (age <60, no prior thrombosis)
- Venesection + aspirin alone — no cytoreduction needed
- Consider hydroxycarbamide if poorly tolerated venesection, progressive splenomegaly, or progressive thrombocytosis
4
Monitoring
- Regular FBC: target Hct <0.45 (this is well evidenced as the threshold for reduced thrombotic risk)
- Annual review: assess for disease transformation (progressive splenomegaly, new cytopenias, increasing fibrosis = post-PV myelofibrosis)
Complications
- Thrombosis: The major cause of morbidity and mortality — both arterial (stroke, MI) and venous (DVT, PE, Budd-Chiari, portal vein thrombosis). Risk reduced by maintaining Hct <0.45
- Haemorrhage: Paradoxical bleeding with extreme thrombocytosis (acquired von Willebrand disease)
- Post-PV myelofibrosis: Progressive marrow fibrosis, worsening cytopenias, massive splenomegaly — 10-20% at 20 years
- Transformation to AML: ~5% at 20 years — higher risk with hydroxycarbamide or prior alkylating agent exposure
- Gout: Hyperuricaemia from high cell turnover
UKMLA Exam Tips
- 1JAK2 V617F positive + low EPO = polycythaemia vera. JAK2 negative + raised EPO = secondary polycythaemia (look for hypoxia, renal tumour, etc.)
- 2Target Hct <0.45 with venesection — this specific threshold is well-evidenced (CYTO-PV trial)
- 3Aquagenic pruritus (itching after hot bath) is a CLASSIC exam clue for PV
- 4Budd-Chiari syndrome (hepatic vein thrombosis) in a young person — always test for JAK2 (PV is a common cause)
- 5Low-dose aspirin for ALL PV patients unless contraindicated
- 6PV vs secondary polycythaemia: PV = low EPO, JAK2+, panmyelosis, splenomegaly. Secondary = raised EPO, no splenomegaly
Put your reading into practice
Topic-specific question practice is not linked for this article yet.
Choose UKMLA questions from the existing bank. General exam practice covers your selected topics; it is not filtered to this article. Your usual question-bank access applies.
Choose UKMLA practiceAfter your session, return to this section to revisit the reading and choose your next review.
Verified Sources & References
related resources
Save your place and choose what comes next
Haematology & Oncology · Article 17 of 28