Polycythaemia Vera

• A myeloproliferative neoplasm characterised by autonomous red blood cell overproduction

• Associated with elevated haematocrit (HCT), often >0.45 in men and women

• Involves risk of thrombotic events (arterial or venous) and progression to myelofibrosis or acute leukaemia

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Symptoms & Clinical Features

• Increased RBC Mass

  • Headache, dizziness, tinnitus

  • Visual disturbances (blurred vision or scotomas)

  • Erythromelalgia (burning pain in extremities with redness)

• Splenomegaly (~70%), possible hepatomegaly (~30%)

• Pruritus (often severe after a hot shower or bath due to histamine release from basophils)

• Thrombosis

  • High risk of both arterial (stroke, MI) and venous events (DVT, PE, hepatic/portal vein thrombosis)

  • Thrombotic complications are a major cause of morbidity and mortality

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Causes

• Primary (True PV)

  • JAK2 mutation in >95% of cases (JAK2 V617F or exon 12)

  • Elevated RBC mass, suppressed EPO level

  • Often elevated WBC and platelets, reflecting panmyelosis

• Secondary

  • Chronic hypoxia (COPD, obstructive sleep apnoea, high altitude)

  • Smoking (↑carboxyhaemoglobin)

  • EPO-secreting tumours (renal cell carcinoma, hepatocellular carcinoma, haemangioblastoma)

  • Inappropriate exogenous EPO use (athletes, doping)

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Investigations

1. Initial Labs

   • FBC: Elevated Hb/HCT, often elevated platelets/WBC

   • EPO level: Low in primary PV, elevated or normal in secondary causes

   • Serum ferritin/iron studies: Identify coexisting iron deficiency or confirm functional iron deficiency (due to repeated venesections)

   • JAK2 mutation testing: Confirmatory for PV if positive

2. Imaging and Further Workup

   • CXR, abdominal ultrasound, or CT if suspicion of an underlying tumour or chronic hypoxia

   • Sleep study if clinically suspect OSA

   • Bone marrow biopsy in uncertain cases or if additional cytopenias suggest other myeloproliferative disorders

3. Monitoring

   • Regular haematocrit checks (target <0.45 to reduce thrombosis risk)

   • Periodic iron studies to monitor for depletion from phlebotomy

   • Assess for new symptoms (e.g. splenomegaly, thrombosis)

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Management

• Phlebotomy (Venesection)

  • First-line to maintain HCT <0.45

  • Decreases blood viscosity, reducing thrombotic complications

  • Long-term venesection may induce functional iron deficiency, which can reduce RBC production

• Cytoreductive Therapy (in high-risk patients)

  • Hydroxyurea

    • Considered if age >60, history of thrombosis, or significant cardiovascular risk factors

    • Monitor FBC regularly for cytopenias

  • Interferon-α

    • Used in pregnancy or younger patients desiring to avoid potential mutagenicity

  • Ruxolitinib

    • JAK1/JAK2 inhibitor for hydroxyurea-intolerant or resistant PV

    • Improves splenomegaly, controls haematocrit, reduces symptoms

• Low-Dose Aspirin

  • Indicated for most PV patients (unless contraindicated) to reduce thrombotic risk

  • Monitor for GI bleeding risk, especially if combined with venesection-induced iron deficiency

• Lifestyle & Supportive Measures

  • Smoking cessation (reduces secondary elevation of carboxyhaemoglobin)

  • Manage OSA if present

  • Encourage hydration to reduce blood viscosity

  • Advise against high-altitude travel if feasible

• Other Considerations

  • Avoid iron supplementation unless clear evidence of symptomatic iron deficiency

  • VTE prophylaxis in high-risk scenarios (long-haul flights, perioperative)

  • Monitor for transformation to myelofibrosis or acute leukaemia

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Notes:

• PV is a chronic condition requiring lifelong monitoring of haematocrit and risk factors for thrombosis

• Exclude secondary causes (chronic hypoxia, EPO-secreting tumours) before diagnosing true PV

• JAK2 positivity >95% in primary PV, typically with suppressed EPO

• Mainstay therapy: phlebotomy + aspirin, cytoreductive therapy for high-risk patients

• Control modifiable cardiovascular risk factors (smoking, hypertension) to mitigate clot risk

• Regular follow-up is crucial: watch for pruritus, splenomegaly changes, or new thrombotic events