Essential thrombocythemia (ET) is a chronic blood cancer in which the bone marrow makes too many platelets, the cell fragments that help blood clot. It is usually caused by an acquired mutation in the JAK2, CALR, or MPL gene. Many people have no symptoms, but ET raises the risk of blood clots and, less often, bleeding. With appropriate risk-based treatment, most patients live a normal or near-normal lifespan.
In my practice, ET is most often discovered by chance on a routine blood test. Below I explain what drives it, how we confirm it, and how treatment is tailored to each person’s risk. It is one of the core conditions in haematology clinics.
What Is Essential Thrombocythemia?
ET belongs to a group of hematologic conditions called myeloproliferative neoplasms (MPNs). In these, a blood stem cell acquires a mutation that makes it overproduce one or more types of blood cell. In ET, the overproduction is mainly of megakaryocytes, the large marrow cells that shed platelets.
A normal platelet count is about 150 to 450 x 10^9 per liter. In ET the count is persistently above 450 and can climb above 1,000. The related MPNs are polycythemia vera, where red cells are mainly increased, and primary myelofibrosis, where the marrow becomes scarred.
ET is usually diagnosed in people in their 50s and 60s, though it also occurs in younger adults, and it is somewhat more common in women.
Causes and Genetic Mutations
ET is not inherited in the usual sense. The mutations are acquired during life in a single marrow stem cell. Three driver genes account for most cases:
| Mutation | Approximate share of ET cases | Typical features |
|---|---|---|
| JAK2 V617F | About 50 to 60% | Older age, higher hemoglobin and white count, higher clot risk |
| CALR | About 20 to 25% | Younger age, higher platelet count, lower clot risk |
| MPL | About 3 to 5% | Similar to CALR in behavior |
| None detected (“triple-negative”) | About 10 to 20% | Often an indolent course; diagnosis relies on marrow findings |
All three mutations switch on the JAK-STAT signaling pathway, which tells megakaryocytes to grow and produce platelets even without the normal hormonal signal. Rarely, ET clusters in families, suggesting an inherited tendency, but this is uncommon.
Signs and Symptoms
Many people with ET feel entirely well. When symptoms occur, they usually come from sluggish blood flow in small vessels or from clots. Elevated platelet counts in ET can cause:
- Headaches, dizziness, or light-headedness
- Visual disturbances such as flashing lights or blurring
- Erythromelalgia: burning pain and redness in the hands and feet, often eased by aspirin
- Tingling in the fingers or toes
- Fatigue and, in some cases, a mildly enlarged spleen
The most serious complications are thrombosis (clots in arteries or veins, including heart attack, stroke, or deep vein thrombosis) and, when counts are very high, bleeding. Over many years, a small minority of patients progress to myelofibrosis or, rarely, acute leukemia.
How Essential Thrombocythemia Is Diagnosed
ET is a diagnosis of exclusion. A high platelet count is far more often reactive, caused by something else, so the first step is to rule out secondary causes of thrombocytosis such as iron deficiency, infection, inflammation, cancer, or a removed spleen.
Key tests
- Repeat platelet count and full blood count with a blood film
- Iron studies and inflammatory markers such as CRP
- Molecular testing for JAK2, CALR, and MPL mutations
- Bone marrow biopsy to show increased, enlarged megakaryocytes and exclude other MPNs
WHO diagnostic criteria in brief
The major criteria are a sustained platelet count of 450 x 10^9/L or more, a bone marrow biopsy typical of ET, exclusion of other myeloid cancers, and a driver mutation. If no mutation is found, another clonal marker or the absence of a reactive cause is required instead.
Treatment Options and Risk Stratification
Treatment aims to prevent clots and bleeding, not simply to normalize numbers. Doctors group patients by risk, classically using age over 60 and a past history of thrombosis, with JAK2 status and cardiovascular risk factors refining the picture.
| Risk group | Typical profile | Usual approach |
|---|---|---|
| Very low / low | Age 60 or under, no prior clot | Observation, with or without low-dose aspirin |
| Intermediate | Over 60, no prior clot, no JAK2 mutation | Low-dose aspirin; cytoreduction considered individually |
| High | Prior clot, or over 60 with JAK2 mutation | Low-dose aspirin plus cytoreductive therapy |
Aspirin
Low-dose aspirin reduces the risk of clotting and relieves small-vessel symptoms. It is used with caution when platelets are extremely high, because this can cause acquired von Willebrand syndrome, a bleeding tendency.
Cytoreductive therapy
These drugs lower platelet production. Hydroxyurea is the usual first choice. Interferon preparations are preferred for younger patients and during pregnancy, and anagrelide is an alternative when others are not tolerated.
Monitoring and lifestyle
Regular blood tests track platelet levels and side effects. Controlling blood pressure, cholesterol, and diabetes, and stopping smoking, matter as much as any drug. Our guide to PLT levels explains the numbers on your report, and our platelets guide covers related conditions.
When to See a Doctor
Ask your doctor about a platelet count that stays above the normal range on repeat testing. Seek emergency care for chest pain, sudden weakness, facial drooping, trouble speaking, a painful swollen leg, or sudden breathlessness, as these may signal a clot. Unusual bleeding or large bruises also need prompt review.
Frequently Asked Questions
Is essential thrombocythemia a cancer?
Yes, it is classed as a chronic blood cancer because it arises from a mutated stem cell. However, it usually behaves very differently from aggressive cancers, and most people live a long life with it.
What platelet count is dangerous in ET?
No single number predicts a clot; age and past thrombosis matter more. Very high counts, above about 1,000 to 1,500 x 10^9/L, raise the risk of bleeding.
Can essential thrombocythemia go away?
ET does not usually resolve on its own. Treatment keeps counts and risks under control, but it is a lifelong condition.
Can I get pregnant with ET?
Many women with ET have successful pregnancies with specialist care. Aspirin and, when needed, interferon are used, while hydroxyurea is avoided.
Key Takeaways
- Essential thrombocythemia is a myeloproliferative neoplasm causing a persistently high platelet count.
- Most cases carry a JAK2, CALR, or MPL mutation.
- Diagnosis requires excluding reactive causes and often a marrow biopsy.
- Treatment is based on clot risk, using aspirin and cytoreductive drugs.
