Essential Thrombocythaemia
BSH Investigation and management of thrombocytosis without JAK2, CALR or MPL mutations Guideline. Date: Dec 2025.
BSH Investigation and Management of Adults and Children Presenting with Thrombocytosis. Date: Apr 2010.
Definition
Essential thrombocythaemia is a MPN characterised by clonal proliferation of megakaryocytes in the bone marrow, resulting in:
- Increased platelet production → persistent thrombocytosis (platelet count >450 x 109/L)
- ↑ Risk of thrombosis and bleeding
MPNs are a group of clonal haematopoietic stem cell disorders characterised by overproduction of mature myeloid lineage cells. The 4 classical myeloproliferative neoplasms are:
- Primary myelofibrosis
- Polycythaemia vera
- Essential thrombocythaemia
- Chronic myeloid leukaemia
share several features:
- Mutations affecting the JAK-STAT signalling pathway (most commonly JAK2, but also CALR or MPL mutations)
- CML is distinct, driven by the Philadelphia chromosome (BCR-ABL fusion gene)
- Bone marrow hypercellularity
- ↑ Risk of thrombosis (particularly in polycythaemia vera and essential thrombocythaemia)
- Risk of transformation to AML
Aetiology
Most cases are caused by mutations in 3 specific genes:
- JAK2 (present in ~50-60% cases)
- CALR (present in 25-35% caes)
- MPL (present in 5-10% cases)
Thrombocytosis may occur in other MPNs, including polycythaemia vera, primary myelofibrosis and CML.
Thrombocytosis may also occur secondary to other conditions, known as reactive thrombocytosis. These causes must be excluded before diagnosing essential thrombocythaemia.
Common causes include:
- Iron deficiency – one of the most common causes
- Acute phase reactions
- Infection
- Inflammation
- Malignancy
- Post-surgery or trauma
- Hyposplenism or splenectomy
- Acute blood loss or haemolysis
Reactive thrombocytosis is more common (~80%) than essential thrombocythaemia.
Clinical Features
Many patients are asymptomatic and diagnosed incidentally on routine blood tests.
Symptoms mainly arise from vascular complications / microvascular disturbances
| Thrombotic complications | Most common complication of essential thrombocythaemia
|
| Microvascular disturbances | Caused by platelet-mediated microvascular occlusion
|
| Other features |
|
Investigation and Diagnosis
To diagnose essential thrombocythaemia, it is important to exclude 1) reactive thrombocytosis and 2) other MPNs
- To exclude reactive thrombocytosis: iron status, CRP / ESR, blood film
- To exclude other MPNs: bone marrow assessment, haematocrit and red cell mass testing (to exclude polycythaemia vera) and BCR-ABL1 testing (to exclude CML)
Key investigation findings:
| Investigation | Key findings |
|---|---|
| FBC | Persistent isolated thrombocytosis (>450 ×10⁹/L) |
| Blood film | May show large / giant platelets |
| Molecular testing | Detection of driver mutation:
This is NOT mandatory for diagnosis, ~10-15% cases of essential thrombocythaemia are ‘triple negative’ – which lack the 3 main driver mutations |
| Bone marrow biopsy – gold standard | Key findings:
|
Management
Management focuses on reducing the risk of thrombotic complications, based on risk:
| Risk group | Description | Management |
|---|---|---|
| Low / intermediate risk |
|
|
| High-risk |
|
Cytoreductive therapy to reduce platelet count
|
All patients should also undergo strict management of cardiovascular risk factors, including treatment of hypertension, diabetes, hyperlipidaemia, and smoking cessation.