Makindo Medical Notes

Related Subjects: |Iron deficiency Anaemia |Haemolytic anaemia |Macrocytic anaemia |Megaloblastic anaemia |Microcytic anaemia |Myelodysplasia |Myelofibrosis

The most important first step in the management of Essential Thrombocythaemia (ET) 🩸 is to confirm the diagnosis and exclude other myeloid neoplasms which may mimic ET (e.g. prefibrotic primary myelofibrosis, masked polycythaemia vera, chronic myeloid leukaemia, refractory anaemia with ring sideroblasts and thrombocytosis).

📖 About

• 📈 Uncontrolled increase in platelet production.
• 🧬 Classified as a myeloproliferative neoplasm (MPN).
• 🤝 Shares features with polycythaemia vera and other MPNs.
• ⚖️ Median survival is >20 years, though risk of complications increases with age.

🧬 Aetiology

• Mutations: JAK2V617F (≈50–60%), CALR (≈20–25%), MPL (≈5–10%).
• Triple-negative ET exists but is rarer and more difficult to diagnose.

📏 Definition / Diagnostic Criteria

• Platelet count ≥450 × 10⁹/L (sustained).
• Presence of JAK2, CALR or MPL mutation.
• If no mutation → must exclude secondary/reactive thrombocytosis.
• Bone marrow: increased mature megakaryocytes in clusters.

🩺 Clinical Features

• 🤕 Microvascular symptoms: headaches, erythromelalgia, visual changes.
• ❤️ Palpitations, dizziness, constitutional symptoms.
• 🩸 Thrombosis → ischaemic stroke, DVT/PE, Budd–Chiari syndrome.
• ⚠️ Paradoxical bleeding (due to acquired vWF defect when platelets >1500 × 10⁹/L).

⚠️ Complications

• Progression to myelofibrosis (10–20% lifetime risk).
• Transformation to acute myeloid leukaemia (AML) (~1–5%).
• Haemorrhage (especially if extreme thrombocytosis).

🧪 Investigations

• Normal CRP and ferritin help exclude reactive causes.
• Platelets often >1000 × 10⁹/L; abnormal giant platelets seen on film.
• Haematinics may be low if chronic bleeding.
• Bone marrow biopsy: increased megakaryocytes, hyperlobulated nuclei.

🔍 Differential of High Platelets

• Acute bleeding or inflammation.
• Iron deficiency anaemia.
• Malignancy, trauma.
• Post-splenectomy reactive thrombocytosis.

💊 Management (per 2018 Algorithm)

• 🧓 Risk stratification: based on age, history of thrombosis, mutation status.
• 🩺 Low risk → aspirin (unless platelets >1500 × 10⁹/L, when bleeding risk ↑).
• 💉 Cytoreduction (hydroxycarbamide 1st line in UK; interferon for young/pregnant; busulfan rarely for older pts).
• 📊 Target platelet count <400–600 × 10⁹/L in high-risk groups.
• 🚫 Avoid aspirin if acquired vWF deficiency present.

📚 References

• Essential thrombocythaemia treatment algorithm (2018)

Cases — Essential Thrombocythaemia (ET)

• Case 1 — Incidental Thrombocytosis: A 62-year-old woman has a routine FBC for hypertension follow-up. Platelets are 720 ×10⁹/L (persistently elevated), Hb and WCC are normal. She is asymptomatic, no splenomegaly. JAK2 mutation positive. Diagnosis: Essential Thrombocythaemia (low-risk, asymptomatic).
• Case 2 — Thrombotic Complication: A 55-year-old man presents with sudden onset left-sided weakness. CT confirms an ischaemic stroke. Bloods show platelets 980 ×10⁹/L, Hb 13 g/dL, WCC 9 ×10⁹/L. He has a history of erythromelalgia (burning pain in hands/feet). JAK2 V617F mutation positive. Diagnosis: ET complicated by arterial thrombosis.
• Case 3 — Bleeding in Extreme Thrombocytosis: A 70-year-old woman presents with recurrent epistaxis and easy bruising. Platelets are 1,600 ×10⁹/L, Hb 12.5 g/dL, WCC 11 ×10⁹/L. Paradoxically, she has an acquired von Willebrand factor deficiency due to very high platelet count. Diagnosis: ET with bleeding complication from acquired vWF deficiency.

Teaching Commentary 🧪

Essential Thrombocythaemia is a myeloproliferative neoplasm characterised by sustained thrombocytosis (>450 ×10⁹/L) due to clonal stem cell proliferation. Most cases are associated with JAK2, CALR, or MPL mutations. Patients may be asymptomatic, or present with arterial/venous thrombosis, microvascular symptoms (erythromelalgia, headaches), or bleeding at very high platelet counts. Management is risk-stratified: low-dose aspirin for most, cytoreduction (e.g., hydroxycarbamide) in high-risk patients (age ≥60, prior thrombosis, platelets >1,500 ×10⁹/L). ET has an indolent course but can transform to myelofibrosis or acute leukaemia.