From the Guidelines
Essential thrombocythemia is a rare chronic blood disorder characterized by the overproduction of platelets in the bone marrow, requiring management to reduce the risk of thrombosis and bleeding complications, with treatment approaches including low-dose aspirin and cytoreductive therapies like hydroxyurea, as recommended by the most recent guidelines 1.
Definition and Pathophysiology
Essential thrombocythemia (ET) is a myeloproliferative neoplasm that involves the overproduction of platelets due to mutations in genes such as JAK2, CALR, or MPL, leading to abnormally high platelet counts, typically above 450,000 platelets per microliter of blood.
Clinical Presentation
Patients with ET may experience symptoms such as headaches, dizziness, burning pain in hands and feet, and visual disturbances, though some remain asymptomatic. The primary concern with ET is the increased risk of blood clots (thrombosis) or, less commonly, bleeding complications.
Risk Assessment and Treatment
Risk assessment considers factors like age, previous clotting events, and cardiovascular risk factors to determine appropriate treatment intensity.
- For low-risk patients, low-dose aspirin (81–100 mg/d) is recommended for vascular symptoms 1.
- For high-risk patients, hydroxyurea or interferons are recommended as first-line cytoreductive therapy 1.
- Cytoreductive therapy is not recommended as initial treatment for low-risk patients, but may be considered for those with symptomatic thrombocytosis or progressive disease-related symptoms.
Management and Prognosis
While ET is a chronic condition requiring ongoing management, many patients have a near-normal life expectancy with proper treatment. It is essential to manage cardiovascular risk factors and monitor for new thrombosis, acquired von Willebrand disease, and disease-related major bleeding.
- All patients with ET should be managed with low-dose aspirin if microvascular disturbances are present 1.
- Cytoreduction is indicated in high-risk patients, with hydroxyurea being the first-line cytoreductive therapy at any age 1.
From the Research
Definition and Characteristics of Essential Thrombocythemia
- Essential thrombocythemia (ET) is a chronic myeloproliferative syndrome characterized by thrombocythemia and increased megakaryocytes in bone marrow, thrombosis and/or hemorrhagic manifestations 2.
- It is a clonal myeloproliferative neoplasm with excessive platelet production, associated with an increased risk of thrombosis and bleeding 3.
- Patients with ET have a persistent platelet count of 450 × 109/L or greater 3.
Clinical Manifestations and Complications
- ET is associated with an increased risk of arterial thrombosis, venous thrombosis, and hemorrhagic complications 3.
- Thrombosis risk is increased among those with a history of thrombosis, age older than 60 years, a JAK2 gene variant, and cardiovascular risk factors 3.
- Approximately 10% of patients with ET develop myelofibrosis and about 3% develop acute myeloid leukemia 3.
- Clinical manifestations in young adults can include potentially life-threatening complications such as myocardial infarctions and stroke 4.
Diagnosis and Risk Stratification
- Formal diagnosis requires the exclusion of other myeloid neoplasms, including prefibrotic MF, polycythemia vera, chronic myeloid leukemia, and myelodysplastic syndromes with ring sideroblasts and thrombocytosis 5.
- Bone marrow morphology typically shows increased number of mature-appearing megakaryocytes distributed in loose clusters 5.
- Approximately 80% of patients express myeloproliferative neoplasm driver mutations (JAK2, CALR, MPL), in a mutually exclusive manner 5.
Treatment and Management
- The main goal of therapy is to prevent thrombosis 5.
- Once-daily low-dose aspirin is advised for all patients and twice daily for low-risk disease 5.
- Cytoreductive therapy is advised for high-risk and optional for intermediate-risk disease 5.
- First-line cytoreductive drugs of choice are hydroxyurea and pegylated interferon-α and second-line busulfan 5.