Polycythaemia/erythrocytosis
Exam Tips
- In OSCE/SAQ, first confirm persistence: repeat FBC after at least 1 week and compare with prior results before labeling chronic erythrocytosis.
- A raised Hb/Hct plus leukocytosis/thrombocytosis, aquagenic pruritus, or splenomegaly strongly points to PV; order JAK2 testing and serum EPO early.
- Use UK threshold memory aid for work-up: persistent Hct >0.52 in men or >0.48 in women.
- Risk-stratify PV for thrombosis (age, prior thrombosis, cardiovascular risk factors) because this determines need for cytoreduction in addition to aspirin and venesection.
- Always screen for secondary causes systematically (hypoxia, smoking/CO, OSA, renal disease, testosterone/EPO use) before concluding idiopathic erythrocytosis.
- See Figure: algorithmic differential of erythrocytosis (relative vs absolute; primary vs secondary) in standard haematology revision texts.
Definition
Polycythaemia/erythrocytosis is a clinical state with persistently raised haemoglobin and haematocrit, reflecting either a true increase in red-cell mass (absolute erythrocytosis) or reduced plasma volume (apparent erythrocytosis). In UK practice, absolute erythrocytosis is subdivided into primary disease (usually polycythaemia vera, a JAK2-driven myeloproliferative neoplasm) and secondary causes mediated by excess erythropoietin, most often from chronic hypoxia or renal pathology.
Pathophysiology
Raised red-cell mass increases whole-blood viscosity, slowing microvascular flow and predisposing to arterial and venous thrombosis; tissue perfusion symptoms (headache, visual disturbance, dizziness) follow from hyperviscosity. In polycythaemia vera (PV), a clonal hematopoietic stem-cell disorder (usually JAK2 V617F, less commonly exon 12) causes erythroid proliferation independent of normal erythropoietin feedback, often with leukocytosis, thrombocytosis, splenomegaly, and inflammatory cytokine-mediated symptoms such as aquagenic pruritus. Secondary erythrocytosis is driven by increased erythropoietin from systemic hypoxia (for example COPD, OSA, smoking/CO exposure, cyanotic heart disease, altitude) or ectopic/renal production (for example renal cell carcinoma, hepatocellular carcinoma). Apparent erythrocytosis reflects contracted plasma volume (for example obesity, alcohol excess, diuretics, smoking) with normal total red-cell mass. See Figure: diagnostic flowchart separating apparent, secondary, and primary erythrocytosis.
Risk Factors
- Age >40 years (PV uncommon before 40; typical diagnosis in later adulthood)
- Previous thrombosis or Budd-Chiari syndrome (including initially normal counts)
- Family history of polycythaemia vera or inherited erythrocytosis syndromes
- Smoking, carbon monoxide exposure, chronic lung disease, cyanotic cardiac disease
- Obstructive sleep apnoea or obesity hypoventilation
- Renal hypoxia states (renal artery stenosis, polycystic kidney disease, hydronephrosis, post-transplant erythrocytosis)
- Erythropoietin-producing tumours (renal, hepatic and selected endocrine/neuro tumours)
- Drugs: testosterone, anabolic steroids, exogenous erythropoietin, diuretics
- Obesity, hypertension, excess alcohol intake (apparent erythrocytosis)
Clinical Features
Symptoms
- Headache/fullness in head or neck, dizziness, sweating
- Fatigue, myalgia, weakness
- Visual disturbance including transient visual loss
- Tinnitus, paraesthesia, cognitive slowing/depersonalisation sensation
- Chest pain or abdominal pain
- Aquagenic pruritus (especially after warm bathing; suggests PV)
- Vasomotor symptoms (flushing, burning pain/redness of digits: erythromelalgia)
- Early satiety/abdominal discomfort from splenomegaly
- Bleeding or bruising episodes
- Symptoms of underlying cause: dyspnoea, snoring/daytime somnolence, cardiorespiratory complaints
Signs
- Plethoric/ruddy complexion
- Conjunctival plethora
- Splenomegaly (supports PV, though not always palpable)
- Hypertension and obesity stigmata
- Low oxygen saturation (<92% on air) or clubbing in hypoxic secondary causes
- Abnormal chest/cardiac examination findings suggesting chronic cardiopulmonary disease
- Palpable abdominal masses (renal/hepatic/uterine lesions causing EPO excess)
Investigations
Management
Lifestyle Modifications
- Stop smoking and avoid carbon monoxide exposure
- Reduce alcohol intake and optimise weight/BMI
- Review and rationalise contributory drugs (for example unnecessary diuretics, androgen misuse)
- Treat underlying hypoxic disease (for example optimise COPD care, manage OSA)
- Maintain hydration and control cardiovascular risk factors (BP, lipids, diabetes)
Pharmacological Treatment
Antiplatelet
- Aspirin 75 mg orally once daily
Used in most PV patients unless contraindicated. Contraindications/cautions: active major bleeding, severe aspirin hypersensitivity, aspirin-exacerbated respiratory disease, active peptic ulceration, significant acquired von Willebrand syndrome from extreme thrombocytosis, concurrent high-bleeding-risk anticoagulation without specialist review.
Cytoreductive therapy (specialist haematology)
- Hydroxycarbamide (hydroxyurea), commonly initiated around 15 mg/kg/day orally then titrated to blood counts
- Interferon alfa preparations (for selected younger patients or pregnancy planning)
- Ruxolitinib (JAK inhibitor) in hydroxycarbamide-intolerant/resistant PV
Indicated for higher thrombotic risk PV or uncontrolled counts/symptoms. Key safety warnings: myelosuppression (monitor FBC closely), infection risk, mucocutaneous ulceration/skin cancer risk with long-term hydroxycarbamide, teratogenicity (avoid in pregnancy; ensure contraception), dose adjustment in renal/hepatic impairment, and urgent review for cytopenias.
Symptom-directed adjuncts
- Non-sedating antihistamines for pruritus (for example cetirizine 10 mg once daily)
Adjunctive only; persistent severe aquagenic pruritus usually requires optimisation of PV control and specialist input.
Surgical / Interventional
- Therapeutic venesection/phlebotomy (typically 350-500 mL per session) to reduce haematocrit, with specialist targets often <0.45 in PV
- Treat underlying structural causes where appropriate (for example tumour-directed surgery in EPO-secreting neoplasms)
Complications
- Arterial thrombosis (especially stroke and myocardial infarction)
- Venous thromboembolism including deep vein thrombosis and splanchnic thrombosis (for example Budd-Chiari)
- Major haemorrhage, particularly with marked thrombocytosis or antithrombotic therapy
- Hyperviscosity-related neurological/visual morbidity
- Progression of PV to post-polycythaemic myelofibrosis
- Transformation to acute myeloid leukaemia
- Treatment-related cytopenias and drug toxicity (notably hydroxycarbamide-associated pancytopenia)
Prognosis
Outcome depends on subtype and cause. In PV, thrombotic risk is significantly above background population but is reduced by antiplatelet therapy, venesection, and risk-adapted cytoreduction; long-term risks include myelofibrotic progression and leukemic transformation. In secondary erythrocytosis, prognosis is mainly determined by the underlying cardiopulmonary, renal, or malignant disorder. Apparent erythrocytosis is associated with increased vascular risk, although the direct benefit of haematocrit reduction alone is less certain than in PV.
Sources & References
🏥BMJ Best Practice(1)
✅NICE Guidelines(1)
- Polycythaemia/erythrocytosis[overview]
📖Textbook References(1)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1351)[context]