Essential thrombocythemia.

Essential thrombocythemia (essential thrombocytosis, primary thrombocythemia) is characterized by an increased platelet count, megakaryocytic hyperplasia, and a tendency to bleed or thromboses. Patients may present with weakness, headache, paresthesia, and bleeding; examination may reveal splenomegaly and digital ischemia. The diagnosis is made based on elevated platelet counts (>500,000/mL), normal red blood cell counts, or normal hematocrit with adequate iron stores and the absence of myelofibrosis, Philadelphia chromosome (or ABL-BCR rearrangement), and other disorders that can cause thrombocytosis. There is no single recommended treatment approach; one option is aspirin 81 mg/day orally. In patients over 60 years of age and in patients with comorbidities, cytostatic therapy is needed to reduce the platelet count.

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Epidemiology

Essential thrombocythemia usually occurs between the ages of 50 and 70.

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Causes essential thrombocythemia

• Chronic inflammatory diseases: RA, inflammatory bowel disease, tuberculosis, sarcoidosis, Wegener's granulomatosis.
• Acute infections.
• Bleeding.
• Iron deficiency.
• Hemolysis.
• Tumors: cancer, Hodgkin's lymphoma (Hodgkin's disease), non-Hodgkin's lymphomas.
• Surgical interventions (splenectomy).
• Myeloproliferative and hematological disorders: polycythemia vera, chronic myelogenous leukemia, sideroblastic anemia, myelodysplastic syndrome (5q-CNH-drome), idiopathic myelodysplasia.

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Pathogenesis

Essential thrombocythemia (ET) usually results from a clonal disorder in a pluripotent hematopoietic stem cell. However, some women who meet the criteria for ET have polyclonal hematopoiesis.

In this pathology, there is increased formation of platelets. The lifespan of platelets is within the normal range, although it can decrease due to sequestration in the spleen. In elderly patients with atherosclerosis, an increase in the number of platelets can lead to severe bleeding or, more often, thrombosis. Bleeding is more typical for extremely pronounced thrombocytosis (platelet level> 1.5 million/μl), which is due to acquired deficiency of the von Willebrand factor.

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Symptoms essential thrombocythemia

The most typical manifestations include weakness, bleeding, non-specific headaches, paresthesia in the hands and feet. Bleeding is usually mild and manifests itself as nosebleeds, mild bruising, or gastrointestinal bleeding. Finger ischemia is possible, and 60% of patients have splenomegaly (the spleen usually does not protrude more than 3 cm from under the edge of the left costal arch). In addition, hepatomegaly may develop. In women, thrombosis may lead to habitual miscarriage.

Although the disease is usually symptomatic, its course is generally benign. Severe complications are rare but can sometimes be life-threatening.

Essential thrombocythemia should be suspected in patients with splenomegaly, as well as in individuals with complaints and symptoms typical of myeloproliferative disease, an increase in the number of platelets or abnormalities in their morphological structure. If essential thrombocythemia is suspected, it is necessary to do a complete blood count, a peripheral blood smear, a myelogram, and a cytogenetic analysis, including determination of the Philadelphia chromosome or BCR-ABL. The platelet count may exceed 1,000,000/μl, but may also be lower (up to 500,000/μl). The platelet count often decreases spontaneously during pregnancy. A peripheral blood smear may reveal platelet aggregates, giant platelets, and megakaryocyte fragments. Megakaryocytic hyperplasia and numerous newly formed platelets are determined in the bone marrow. Iron reserves are preserved in the bone marrow. Unlike other myeloproliferative disorders that may cause thrombocytosis, essential thrombocythemia is characterized by normal hematocrit, MCV, and iron levels, the absence of the Philadelphia chromosome and BCR-ABL translocation (found in chronic myelogenous leukemia), the absence of teardrop-shaped red blood cells, and the absence of significant bone marrow fibrosis (found in idiopathic myelofibrosis). In addition, the diagnosis requires exclusion of other pathological conditions that may cause secondary thrombocytosis.

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Differential diagnosis

Secondary thrombocytosis may develop in chronic inflammatory diseases, acute infection, bleeding, iron deficiency, hemolysis, or tumors. Platelet function is usually normal. However, in myeloproliferative diseases, platelet aggregation disorders are found in 50% of patients. In contrast to primary thrombocythemia, it does not increase the risk of thrombotic or hemorrhagic complications unless patients have arterial disease or prolonged immobilization. In secondary thrombocytosis, the platelet count is usually <1,000,000/μL; the cause can sometimes be determined by history taking, physical examination, radiography, or blood tests. Treatment of the underlying disorder usually returns the platelet count to normal.

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Treatment essential thrombocythemia

There is no consensus on when to initiate therapy. For mild vasomotor symptoms (eg, headache, mild digital ischemia, erythromelalgia) and to reduce the risk of thrombosis in low-risk patients, aspirin 81 mg orally once daily is sufficient. Because the prognosis is generally good, the use of potentially toxic platelet-lowering therapies should be limited. Patients with significant bleeding require platelet-lowering therapy. Patients over 60 years of age with a history of thrombosis or with comorbidities that increase the risk of thrombosis should receive platelet-lowering agents. The use of platelet-lowering agents in asymptomatic patients under 60 years of age requires further study. Most pregnant women are prescribed aspirin.

Myelosuppressive therapy, which reduces platelet levels, typically includes anagrelide, hydroxyurea, or interferon a. The goal of therapy is to reduce platelet counts to <450,000/μL without significant clinical toxicity or suppression of other hematopoietic lineages. Because anagrelide and hydroxyurea cross the placenta, they are not used in pregnancy; interferon can be used in pregnant women.

Plateletpheresis may be used to rapidly reduce platelet counts (e.g., in cases of severe bleeding or thrombosis; prior to emergency surgery), but this procedure is rarely necessary. Because of the long half-life of platelets (7 days), hydroxyurea and anagrelide do not provide a rapid effect.

Forecast

The life expectancy of patients is almost not reduced. Transformation into acute leukemia occurs in less than 2% of patients, but its frequency may increase after cytostatic therapy, especially with the use of alkylating agents.

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