Makindo Medical Notes

🩸 Polycythaemia Vera (PV) is a clonal myeloproliferative neoplasm caused by mutations (usually JAK2 V617F) leading to uncontrolled proliferation of erythrocytes, platelets, and WBCs. EPO levels are typically suppressed. With timely treatment (venesection, cytoreduction, aspirin), survival can approach normal.

📖 About

• Clonal disorder of myeloid progenitor cells.
• Excess production of RBCs, WBCs, and platelets.
• Most cases: JAK2 V617F mutation (activates JAK–STAT signalling).
• Erythropoietin (EPO) levels usually low.
• Mortality reduced significantly by treatment (thrombosis prevention, cytoreduction).

⚙️ Aetiology & Pathogenesis

• JAK2 mutation → constitutive signalling → growth factor hypersensitivity.
• Uncontrolled proliferation of myeloid lineages (erythroid, granulocytic, megakaryocytic).
• Classified as a chronic myeloproliferative neoplasm.

🩺 Clinical Features

• Typically affects middle-aged & older adults.
• Plethora (ruddy complexion, dusky cyanosis).
• Neurological: headache, dizziness, visual disturbance, TIAs, stroke.
• Splenomegaly (~70%) & hepatomegaly (~50%).
• Cardiac: hypertension, angina, ↑ risk of MI.
• Pruritus after hot baths/showers (histamine release).
• Erythromelalgia (burning pain/red extremities from microvascular occlusion).
• Thrombosis: DVT, PE, mesenteric or cerebral clots.
• Bleeding tendency (esp. acquired vWF deficiency with high platelets).
• Hyperuricaemia → gout, renal stones.

🧪 Diagnostic Criteria (WHO 2016)

Diagnosis requires all 3 major criteria, or the first 2 major + the minor criterion.

• Major:
  • Hb >16.5 g/dL (men) or >16.0 g/dL (women), OR Hct >49% (men), >48% (women), OR ↑ red cell mass.
  • Bone marrow: hypercellular, trilineage proliferation (panmyelosis).
  • JAK2 V617F (or exon 12) mutation present.
• Minor:
  • Subnormal serum EPO.

🔍 Investigations

• FBC: ↑ Hb/Hct, WBC >12 ×10⁹/L, platelets >450 ×10⁹/L.
• Blood film: ↑ cells, otherwise bland.
• Bone marrow biopsy: trilineage hyperplasia.
• JAK2 mutation analysis: diagnostic in ~95%.
• EPO: low.
• Urate: often raised (cell turnover).
• B12: often high (↑ binding proteins from neutrophils).
• Abdominal ultrasound/CT: splenomegaly.

🧾 Differentials

• Secondary polycythaemia: hypoxia (lung disease, smoking, altitude), renal tumours (↑ EPO).
• Relative polycythaemia: plasma volume depletion (dehydration, diuretics).

⚠️ Complications

• Thrombosis (arterial/venous).
• Acquired bleeding tendency (vWF deficiency).
• Hyperuricaemia → gout, renal stones.
• Progression → myelofibrosis or AML (rare).

💊 Management

• Venesection (phlebotomy): target Hct <45% (men), <42% (women).
• Low-dose aspirin (75–100 mg OD) unless contraindicated.
• Cytoreductive therapy:
  • Hydroxyurea (hydroxycarbamide) = first-line.
  • Interferon-α (younger pts, pregnancy).
  • Anagrelide for platelet control.
• Allopurinol for hyperuricaemia/gout prevention.
• Pruritus management: antihistamines, SSRIs, interferon-α.
• Avoid iron supplementation unless true deficiency with symptoms.
• Lifestyle: stop smoking, control CV risk factors.

📚 References

• NICE Guideline NG35: Myeloproliferative Neoplasms
• Blood Journal: Polycythaemia Vera
• Cancer Research UK