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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Persistently raised platelet count (>450 × 10⁹/L) from clonal myeloproliferation — a diagnosis of exclusion after ruling out reactive causes
- Driver mutations: JAK2 V617F (~55%), CALR (~25%), MPL (~5%). ~15% are "triple-negative"
- Risk of thrombosis (arterial > venous) and paradoxical bleeding with extreme thrombocytosis (acquired von Willebrand disease)
- Low-risk (age <60, no thrombosis history): observation or aspirin 75 mg daily
- High-risk (age ≥60 OR prior thrombosis): hydroxycarbamide + aspirin. Target platelets <400 × 10⁹/L
Overview
Essential thrombocythaemia (ET) is a chronic myeloproliferative neoplasm characterised by sustained megakaryocyte proliferation leading to persistent thrombocytosis. It is a diagnosis of exclusion — reactive thrombocytosis (infection, inflammation, iron deficiency, post-splenectomy) is far more common and must be ruled out. ET has the most favourable prognosis of the myeloproliferative neoplasms, with near-normal life expectancy in many patients, but carries a risk of thrombosis and a small long-term risk of transformation to myelofibrosis or AML.
Epidemiology
ET has an incidence of approximately 1-2 per 100,000 per year. The median age at diagnosis is 55-60 years, with a second smaller peak in younger adults (30-40 years). It is slightly more common in women. ET is the most common MPN to present in pregnancy. Life expectancy is near-normal for most patients, particularly those with CALR mutations.
Clinical Features
Symptoms
Often asymptomatic — incidental finding of raised platelets on routine FBC
Headache, dizziness, visual disturbance (microvascular symptoms)
Erythromelalgia — burning pain and redness in hands and feet (responds to aspirin)
Thrombosis — arterial (stroke, TIA, MI) or venous (DVT, PE, unusual site thrombosis)
Bleeding — particularly with very high platelet counts (>1000-1500 × 10⁹/L) due to acquired VWD
Signs
Often no abnormal findings on examination
Mild splenomegaly (40%)
Digital ischaemia or gangrene (rare)
Investigations
First-line
FBCPersistently raised platelets >450 × 10⁹/L (often 600-1000+). Hb and WCC usually normal (unlike PV)
Blood filmLarge platelets, platelet clumps. No red cell abnormalities (unlike myelofibrosis — no tear-drop cells)
JAK2 V617F, CALR, MPL mutationsTest sequentially: JAK2 first → if negative, CALR → if negative, MPL. ~85% will have one mutation. Triple-negative = higher suspicion for reactive cause
Second-line
Iron studies, CRP, ESRExclude reactive thrombocytosis (iron deficiency, infection, inflammation are the commonest causes of raised platelets)
Bone marrow biopsyShows increased megakaryocytes — large, hyperlobated, in clusters. Helps distinguish ET from pre-fibrotic myelofibrosis
Von Willebrand factor studiesIf platelets >1000 × 10⁹/L — check for acquired VWD (low VWF activity) before giving aspirin
Specialist
CytogeneticsUsually normal in ET. Abnormalities suggest alternative diagnosis (MDS, CML)
BCR-ABL1 PCRExclude CML — can present with isolated thrombocytosis. Must be checked in all cases
1
Risk stratification
- Low risk: age <60 AND no history of thrombosis AND JAK2 negative
- Intermediate risk: age <60, no thrombosis, JAK2 positive
- High risk: age ≥60 OR previous thrombosis
2
Low-risk ET
- Observation or aspirin 75 mg daily (if JAK2 positive or cardiovascular risk factors)
- AVOID aspirin if platelets >1500 × 10⁹/L — risk of acquired VWD and bleeding
3
High-risk ET
- Hydroxycarbamide (first-line cytoreductive) — target platelets <400 × 10⁹/L
- Plus aspirin 75 mg daily (if no acquired VWD)
- Alternative: anagrelide (second-line — specifically reduces platelets via megakaryocyte inhibition)
- Interferon-alpha: preferred in young patients and pregnancy (hydroxycarbamide is teratogenic)
4
ET in pregnancy
- Aspirin 75 mg daily (from confirmation of pregnancy to 36 weeks)
- High-risk: add LMWH prophylaxis
- Interferon-alpha if cytoreduction needed (hydroxycarbamide and anagrelide are contraindicated)
Complications
- Thrombosis: Arterial > venous. Stroke, MI, DVT/PE, unusual sites. The major clinical risk
- Haemorrhage: Paradoxical with very high platelets (>1000-1500) — acquired VWD. Check VWF activity before aspirin
- Transformation to myelofibrosis: ~5-10% at 15 years — progressive splenomegaly, cytopenias, tear-drop cells
- Transformation to AML: ~1-2% at 15 years — lower risk than PV
UKMLA Exam Tips
- 1Reactive thrombocytosis is FAR more common than ET — always exclude iron deficiency, infection, inflammation, malignancy, and post-splenectomy first
- 2Must test BCR-ABL to exclude CML — CML can present with isolated thrombocytosis
- 3Very high platelets (>1000-1500) = risk of BLEEDING (not thrombosis) due to acquired VWD — do NOT give aspirin
- 4JAK2 positive = higher thrombotic risk, behaves more like PV. CALR positive = lower thrombotic risk, better prognosis
- 5Hydroxycarbamide is TERATOGENIC — use interferon-alpha in pregnancy
- 6Erythromelalgia (burning hands/feet) = responds dramatically to low-dose aspirin
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