Thrombocytosis and Essential Thrombocythaemia
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Direct answer
Essential thrombocythaemia is a clonal myeloproliferative neoplasm with a sustained platelet count above 450 × 10^9/L, usually driven by JAK2, CALR or MPL mutations, and it is separated from reactive thrombocytosis by these markers and by the marrow pattern. Management is risk-adapted: low-dose aspirin for low-risk patients, and cytoreduction with hydroxyurea for those over 60 or with previous thrombosis.
What you must remember
- Threshold: a platelet count above 450 × 10^9/L is the usual cut-off for thrombocytosis, and it must persist before a diagnosis is considered.
- Reactive causes: iron deficiency is the commonest, followed by infection, inflammation, haemorrhage, malignancy and splenectomy; these rarely exceed about 1000 × 10^9/L.
- Driver mutations: JAK2 V617F is found in about half of patients, CALR in about a fifth and MPL in a small minority; triple-negative cases lack all three.
- Marrow findings: clustered, large, mature megakaryocytes with hyperlobulated nuclei, without the dysplasia seen in myelodysplasia.
- Thrombosis: arterial and venous events occur, including splanchnic thrombosis such as Budd-Chiari syndrome, with JAK2 positivity as a risk factor.
- Risk stratification: age over 60 and previous thrombosis mark high risk, and cytoreduction is reserved for these patients.
- Cytoreduction: hydroxyurea is first line for high-risk disease, while anagrelide is an alternative and pegylated interferon is preferred in pregnancy.
- Bleeding: very high platelet counts can cause acquired von Willebrand syndrome, so antiplatelet therapy needs caution in extreme thrombocytosis.
Reactive versus clonal thrombocytosis
The first task is separating a reactive rise from a clonal disorder, because the management differs entirely. The table sets out the key contrasts.
| Feature | Reactive thrombocytosis | Essential thrombocythaemia |
|---|---|---|
| Typical platelet count | Usually below 1000 × 10^9/L | Often above 450 × 10^9/L, sometimes higher |
| Underlying cause | Iron deficiency, infection, inflammation, haemorrhage | Clonal myeloproliferation |
| Driver mutation | Absent | JAK2, CALR or MPL in most |
| Marrow | Reactive megakaryocytes | Clustered, large, mature megakaryocytes |
| Management | Treat the cause | Risk-adapted aspirin and cytoreduction |
Work-up begins with iron studies and CRP, since iron deficiency is the commonest reactive cause and the count normalises once it is corrected. A count that persists after the reactive cause is treated, together with a driver mutation or a characteristic marrow pattern, establishes the diagnosis.
Thrombotic risk is the main determinant of treatment. Patients over 60 and those with previous thrombosis are assessed for cytoreduction, while the remainder receive low-dose aspirin, with decisions made according to current guidance and specialist review.
Where the exam tries to catch you
Thrombocytosis questions usually test reactive versus clonal causes and the choice of drug in special groups.
- Trap: diagnosing essential thrombocythaemia without checking iron status Correct: iron deficiency is the commonest reactive cause, and correcting it normalises the platelet count.
- Trap: using aspirin alone in a high-risk patient Correct: patients over 60 or with prior thrombosis need cytoreduction, usually with hydroxyurea, in addition to aspirin.
- Trap: starting antiplatelet therapy without considering bleeding in extreme thrombocytosis Correct: very high counts cause acquired von Willebrand syndrome, so bleeding risk must be weighed.
- Trap: choosing hydroxyurea for a pregnant woman with essential thrombocythaemia Correct: hydroxyurea is teratogenic, so pegylated interferon is preferred during pregnancy.
Frequently asked questions
What platelet count defines thrombocytosis?
A platelet count above 450 × 10^9/L is the usual threshold for thrombocytosis. Counts this high need evaluation for reactive causes such as iron deficiency and infection, and for clonal disease if these are excluded.
What mutations drive essential thrombocythaemia?
Essential thrombocythaemia is usually driven by JAK2 V617F, CALR or MPL mutations, with JAK2 the most common. Patients lacking all three are called triple-negative, and they need careful exclusion of other myeloid neoplasms.
Which drug is first line for cytoreduction in essential thrombocythaemia?
Hydroxyurea is the first-line cytoreductive drug for high-risk essential thrombocythaemia, commonly given with low-dose aspirin. Anagrelide is an alternative for patients who cannot tolerate hydroxyurea, though it can cause headache and palpitations.
How is essential thrombocythaemia managed in pregnancy?
Pegylated interferon alpha is preferred for women with essential thrombocythaemia who are pregnant or planning pregnancy, because hydroxyurea is teratogenic. Low-dose aspirin is commonly continued during pregnancy under specialist supervision.
What is the role of aspirin in essential thrombocythaemia?
Low-dose aspirin reduces thrombotic risk in low-risk patients and often relieves erythromelalgia, the burning pain in the hands and feet typical of the disorder. It is used with caution when platelet counts are very high, because of bleeding risk from acquired von Willebrand syndrome.