Essential Thrombocythaemia

Essential thrombocythaemia (ET), also known as essential thrombocytosis or primary thrombocytosis, is a rare chronic blood cancer classified under myeloproliferative neoplasms. It is characterised by the overproduction of platelets by megakaryocytes in the bone marrow. This condition may rarely progress to acute myeloid leukaemia or myelofibrosis.

Signs and Symptoms

Most individuals with ET are asymptomatic at diagnosis, which is often incidentally discovered through elevated platelet levels on a routine complete blood count (CBC). Common symptoms include fatigue, headache, nausea, vomiting, abdominal pain, visual disturbances, dizziness, fainting, and numbness in the extremities. Furthermore, increased white blood cell count, reduced red blood cell count, and an enlarged spleen are typical signs. Bleeding and blood clots, such as deep vein thrombosis or pulmonary embolism, are also prevalent due to dysfunctional platelets.

Cause

In ET, megakaryocytes are unusually sensitive to growth factors, leading to activated platelets and an elevated platelet count, which increases the risk of forming blood clots. A significant genetic component is involved in ET. Approximately 40-50% of ET cases are associated with a JAK2 mutation (V617F), a member of the Janus kinase family. Mutations in the CALR gene, which encodes calreticulin, are also common, particularly in JAK2-negative patients. These mutations affect the last exon, causing a reading frame shift that generates a novel terminal peptide and a loss of the endoplasmic reticulum KDEL retention signal. Lastly, MPL mutations, though less common, play a role in ET by constantly activating the thrombopoietin receptor, leading to continuous cell proliferation.

Diagnosis

The diagnosis of ET requires specific criteria. The platelet count must exceed 400 × 10^3/μL for at least two months, and the presence of the acquired V617F JAK2 mutation is also a significant factor. It is very important to rule out other causes of reactive thrombocytosis, iron deficiency, polycythaemia vera, chronic myeloid leukaemia, myelofibrosis, and myelodysplastic syndromes to confirm ET.

Treatment

Indications

Not all patients with ET require immediate treatment. Treatment decisions are based on the patient's risk of bleeding or thrombotic events, which are determined by age, medical history, and lifestyle. Low-risk individuals may only require aspirin, whereas high-risk patients are treated with cytoreductive therapies such as hydroxycarbamide, interferon-α, or anagrelide.

Agents

Hydroxycarbamide, interferon-α, and anagrelide help lower the platelet count. Low-dose aspirin is used to prevent blood clots unless the platelet count is excessively high, which could increase bleeding risk. The PT1 study indicated that hydroxyurea plus aspirin is more effective in reducing arterial thrombosis and severe bleeding compared to anagrelide plus aspirin. However, hydroxycarbamide showed a higher risk of venous thrombosis. In cases with extremely high platelet counts exceeding 1 million, plateletpheresis may be employed to rapidly reduce platelet levels and lower thrombosis risk.

Prognosis

Essential thrombocythaemia is typically a slowly progressive disorder with long asymptomatic periods interrupted by thrombotic or hemorrhagic events. Proper medical management can control platelet counts and reduce the risk of these events, leading to a normal lifespan for well-controlled ET patients. ET is the myeloproliferative neoplasm least likely to progress to acute myeloid leukaemia.

Epidemiology

The incidence of ET ranges from 0.6 to 2.5 per 100,000 individuals per year, with a median age at onset of 65-70 years. It is more common in females than males, and the incidence in children is notably lower at 0.09 per 100,000 per year.

Pregnancy

Hydroxycarbamide and anagrelide are contraindicated during pregnancy and nursing due to potential risks. ET can increase the risk of miscarriage threefold. Close monitoring of the mother and foetus is essential throughout pregnancy. Low-dose low molecular weight heparin, such as enoxaparin, may be used. In life-threatening situations, plateletpheresis can be employed to rapidly reduce platelet counts.

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Self-assessment MCQs (single best answer)

What is the primary characteristic of essential thrombocythaemia (ET)?

Which gene mutation is associated with approximately 40-50% of ET cases?

What is a common symptom of ET?

What is the typical platelet count required for the diagnosis of ET?

Which treatment is indicated for low-risk ET patients to prevent blood clots?

Which therapy is contraindicated during pregnancy for ET patients?

What is the potential progression of ET in rare cases?

Which study indicated that hydroxyurea plus aspirin is more effective in reducing arterial thrombosis?

What is the median age at onset for ET?

ET is classified under which group of disorders?