Polycythaemia Vera (Primary Polycythaemia) ✅

Related Subjects: |Leukaemias in General |Acute Promyelocytic Leukaemia |Acute Myeloblastic Leukaemia (AML) |Acute Lymphoblastic Leukaemia (ALL) |Chronic Lymphocytic leukaemia (CLL) |Chronic Myeloid Leukaemia (CML) |Hairy Cell Leukaemia |Differentiation syndrome |Tretinoin (All-trans-retinoic acid (ATRA) ) |Haemolytic anaemia |Immune(Idiopathic) Thrombocytopenic Purpura (ITP) |Polycythaemia Vera (Primary Polycythaemia)

🩸 Polycythaemia Vera (PV) is a clonal myeloproliferative neoplasm in which the bone marrow overproduces red cells, and often also white cells and platelets. 🧬 In most people it is driven by a JAK2 mutation, most commonly JAK2 V617F; a smaller proportion have JAK2 exon 12 mutations. 📉 Serum erythropoietin (EPO) is usually low or suppressed. ⚠️ The major clinical danger is thrombosis, so treatment is focused on reducing vascular risk with venesection, low-dose aspirin, and cytoreduction when indicated.

📖 About

• PV is a chronic myeloproliferative neoplasm arising from a clonal stem-cell disorder.
• It causes overproduction of red blood cells, and often also platelets and white cells.
• The excess red-cell mass raises blood viscosity, which contributes to arterial and venous thrombosis.
• With appropriate treatment, thrombotic risk and long-term outcomes improve substantially.

⚙️ Aetiology & Pathogenesis

• 🧬 JAK2 mutation causes constitutive activation of the JAK–STAT pathway.
• This makes myeloid progenitors hypersensitive to growth signals and leads to trilineage proliferation (erythroid, granulocytic, and megakaryocytic).
• 📉 Because red-cell production becomes relatively autonomous, EPO levels are usually suppressed.

🩺 Clinical Features

• Typically presents in middle age or later life, though younger adults can be affected.
• Plethora — ruddy complexion, facial redness, or dusky appearance.
• 🧠 Headache, dizziness, tinnitus, visual disturbance, TIAs, or stroke-like symptoms.
• 🫀 Hypertension, angina, and increased risk of arterial events such as MI.
• 🖐️ Erythromelalgia — burning pain and redness of hands or feet due to microvascular disturbance.
• 🚿 Aquagenic pruritus — itching after a hot bath or shower is highly characteristic.
• 🫃 Splenomegaly is common and may cause abdominal fullness or early satiety.
• 🩸 Thrombosis can occur in typical sites (DVT/PE) or unusual sites such as splanchnic or cerebral veins.
• 🩹 Bleeding can also occur, especially if the platelet count is very high and causes acquired von Willebrand syndrome.
• 🧪 Hyperuricaemia may lead to gout or renal stones.

🧪 Diagnostic Criteria (WHO 2016)

Diagnosis requires all 3 major criteria, or the first 2 major criteria plus the minor criterion. This section is labelled specifically as WHO 2016 criteria.

• Major criteria:
  • Hb >16.5 g/dL in men or >16.0 g/dL in women, or Hct >49% in men or >48% in women, or increased red-cell mass.
  • Bone marrow biopsy showing hypercellularity with panmyelosis.
  • Presence of a JAK2 V617F or JAK2 exon 12 mutation.
• Minor criterion:
  • Subnormal serum EPO.

🔍 Investigations

• FBC: raised Hb / haematocrit; often raised white cells and platelets as well.
• Blood film: may show erythrocytosis and thrombocytosis but is often otherwise non-specific.
• JAK2 mutation testing: essential in diagnosis; the great majority of patients have a JAK2 mutation.
• Serum EPO: usually low.
• Bone marrow biopsy: shows trilineage hyperplasia / panmyelosis and helps confirm the diagnosis.
• Urate: often raised.
• Abdominal examination / imaging: assess for splenomegaly if clinically relevant.

🧾 Differentials

• Secondary erythrocytosis: chronic hypoxia, smoking, sleep apnoea, lung disease, cyanotic heart disease, testosterone excess, renal disease or EPO-producing tumours.
• Relative erythrocytosis: reduced plasma volume, for example dehydration or diuretic use.

⚠️ Complications

• 🩸 Arterial and venous thrombosis — the major cause of morbidity.
• 🩹 Bleeding, especially when platelet counts are very high.
• 🧪 Hyperuricaemia with gout or renal stones.
• 🫀 Symptom burden from pruritus, microvascular disturbance, and splenomegaly.
• 🔁 Progression to myelofibrosis.
• 🧬 Rare transformation to acute myeloid leukaemia.

💊 Management

• Venesection (phlebotomy): target haematocrit <45%.
• Low-dose aspirin unless contraindicated.
• Cytoreductive therapy for patients at higher thrombotic risk, with uncontrolled counts/symptoms, or where venesection alone is insufficient:
  • Hydroxycarbamide (hydroxyurea) is a common first-line option.
  • Interferon-α is particularly useful in younger patients and in pregnancy.
  • Ruxolitinib may be used in selected cases when standard cytoreduction is not suitable or inadequate.
• Manage complications: pruritus, thrombosis, gout, bleeding risk, and symptom burden.
• Cardiovascular risk reduction: stop smoking, manage BP, diabetes, and lipids.
• Iron: avoid routine iron replacement unless there is a clear indication and haematology agrees, because replacing iron can drive erythropoiesis.

🧠 Clinical Pearls

• PV is not just “high Hb” — it is a clonal stem-cell disease.
• The most important management goal is preventing thrombosis.
• Aquagenic pruritus + erythrocytosis + low EPO is a classic exam combination.
• Always think about secondary erythrocytosis before assuming PV.
• Very high platelets can paradoxically increase bleeding risk because of acquired von Willebrand syndrome.

🩺 Case 1 – Classic PV Presentation

A 67-year-old man presents with headache, facial plethora, pruritus after hot showers, and a haematocrit of 0.56. His JAK2 V617F test is positive and serum EPO is suppressed. Management: 🩸 Venesection to bring the haematocrit below 45%, start low-dose aspirin if not contraindicated, and refer to haematology for formal risk stratification and discussion of cytoreduction. Avoid: ❌ Missing the thrombotic risk by treating this as “just dehydration” or “high haemoglobin”.

🩺 Case 2 – Thrombotic Complication

A 58-year-old woman presents with abdominal pain and is found to have splanchnic vein thrombosis. Blood tests show raised haematocrit and thrombocytosis. Management: 🧬 Investigate for an underlying myeloproliferative neoplasm including JAK2 mutation testing, start thrombosis treatment, and involve haematology early because unusual-site thrombosis is a classic clue to PV or related MPNs. Avoid: ❌ Stopping at anticoagulation alone without looking for the underlying marrow disorder.

🩺 Case 3 – Younger Patient Requiring Cytoreduction

A 34-year-old woman with confirmed PV has recurrent venesection requirements, troublesome aquagenic pruritus, and rising platelets. Management: 💊 Continue haematocrit control, optimise aspirin if appropriate, and discuss interferon-α with haematology because she is young and may wish to preserve pregnancy options. Avoid: ❌ Assuming hydroxycarbamide is automatically the best first choice in every younger patient.

📚 References

• British Society for Haematology. Diagnosis and management of polycythaemia vera.
• NICE CKS. Polycythaemia / erythrocytosis.
• Cancer Research UK. Polycythaemia vera.
• WHO 2016 myeloid neoplasm diagnostic criteria / classification reviews.