Essential Thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by the clonal proliferation of megakaryocytes, leading to persistent thrombocytosis (elevated platelet counts) and an increased risk of thrombosis and hemorrhage. The disorder is driven by mutations in the JAK2, CALR, or MPL genes, with JAK2 V617F being the most common. ET is typically diagnosed in middle-aged and older adults, though it can occur at any age. The clinical course of ET is variable, with many patients remaining asymptomatic for years, while others may experience thrombotic events, hemorrhagic complications, or disease progression to myelofibrosis or, rarely, acute myeloid leukemia (AML).

The diagnosis of Essential Thrombocythemia is established through a combination of clinical evaluation, laboratory tests, and bone marrow examination, following the World Health Organization (WHO) criteria. Key diagnostic criteria include a sustained platelet count ≥450 × 10^9/L, the presence of clonal mutations (JAK2, CALR, or MPL), and exclusion of other causes of reactive thrombocytosis, such as iron deficiency or inflammation. Bone marrow biopsy typically shows hyperplasia of megakaryocytes with enlarged, mature forms and minimal to no increase in reticulin fibrosis. In the absence of a clonal marker, diagnosis is more challenging and requires careful exclusion of reactive causes and other MPNs. Additional tests include serum erythropoietin levels, which are usually normal or slightly elevated in ET, and screening for secondary causes of thrombocytosis, including iron studies, inflammatory markers, and splenic imaging.

The prognosis of ET is generally favorable, with many patients living for decades without significant morbidity. However, the risk of thrombotic and hemorrhagic events, as well as progression to myelofibrosis or AML, necessitates careful risk stratification. Age >60 years, history of thrombosis, and JAK2 V617F mutation are the primary risk factors for thrombosis and guide the intensity of treatment. Other factors, such as leukocytosis, cardiovascular risk factors, and mutation allele burden, may also influence risk. Prognostic models, such as the International Prognostic Score for Thrombosis in ET (IPSET-Thrombosis), are used to stratify patients into low, intermediate, and high-risk categories, guiding therapeutic decisions. The risk of progression to myelofibrosis or AML is relatively low, with transformation rates of approximately 5-10% over 20 years.

Ongoing assessment in ET involves regular monitoring of hematologic parameters and symptom burden. Complete blood counts (CBC) are performed routinely to track platelet, leukocyte, and hemoglobin levels, with a focus on maintaining platelet counts within target ranges. Bone marrow biopsy may be repeated in cases of suspected disease progression or to assess the degree of fibrosis if myelofibrosis is suspected. Molecular monitoring, including JAK2 V617F, CALR, and MPL mutation analysis, provides additional insights into disease activity and can guide treatment decisions. Symptom assessment tools, such as the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), are useful for evaluating patient-reported outcomes, including symptoms such as headaches, dizziness, and erythromelalgia (burning pain and redness in the extremities). Periodic imaging studies, such as spleen ultrasound or MRI, may be indicated in cases of splenomegaly or if there is concern for extramedullary hematopoiesis.

The treatment of Essential Thrombocythemia focuses on reducing thrombotic risk and managing symptoms while minimizing treatment-related complications. Low-risk patients, particularly those under 60 years of age without a history of thrombosis, may be managed with low-dose aspirin (81-100 mg daily) alone. For high-risk patients (age >60 years, history of thrombosis, or JAK2 V617F mutation), cytoreductive therapy is recommended to lower platelet counts. Hydroxyurea is the first-line cytoreductive agent, with anagrelide as an alternative for those intolerant to hydroxyurea or in whom hydroxyurea is contraindicated. Interferon-alpha, including its pegylated form, is increasingly used, especially in younger patients or during pregnancy, due to its ability to control platelet counts and potential for disease modification. Ruxolitinib, a JAK1/2 inhibitor, may be considered in selected cases, particularly those with significant splenomegaly or severe symptoms unresponsive to standard therapies. In rare cases of ET progressing to myelofibrosis or AML, more aggressive treatments, including allogeneic stem cell transplantation, may be indicated. Regular monitoring and adjustment of therapy based on hematologic response, symptom control, and risk stratification are essential to optimizing long-term outcomes.