Essential thrombocythemia

Essential thrombocythemia (essential thrombocytosis, primary thrombocythemia) is characterized by an increase in the number of platelets, megakaryocytic hyperplasia and a tendency to bleeding or thrombosis. Patients may complain of weakness, headaches, paresthesias, bleeding; splenomegaly and ischemia of the fingers can be detected during the examination. The diagnosis is made when revealing an increased number of platelets (> 500,000 / ml), normal red blood cell count or normal hematocrit with adequate iron stores, absence of myelofibrosis, Philadelphia chromosome (or ABL-BCR rearrangement) and other diseases that can cause thrombocytosis. There is no single recommended approach to therapy; One of the treatment options is aspirin at 81 mg / day. In patients older than 60 years and patients with comorbidities, cytostatic therapy is necessary to reduce the number of platelets.

[1], [2], [3], [4]

Epidemiology

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

[5], [6], [7], [8]

Causes of the essential thrombocythemia

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

[9], [10]

Pathogenesis

Essential thrombocythemia (ET), as a rule, develops as a result of a clonal disorder in a polypotent hematopoietic stem cell. However, polyclonal hematopoiesis is observed in some women who meet the criteria for diagnosis of essential thrombocythemia.

With this pathology, there is an increased formation of platelets. Life expectancy of platelets is within the normal range, although it may 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, to thrombosis. Bleeding is more characteristic of extremely marked thrombocytosis (platelet count> 1.5 million / μl), due to the acquired Willebrand factor deficiency.

[11], [12], [13], [14], [15], [16]

Symptoms of the essential thrombocythemia

The most characteristic manifestations include weakness, bleeding, non-specific headaches, paresthesias in the hands and feet. Bleeding is usually mild and manifested by nosebleeds, mild bruising or gastrointestinal bleeding. Finger ischemia is possible, splenomegaly is detected in 60% of patients (the spleen usually does not protrude more than 3 cm from the edge of the left costal arch). In addition, the development of hepatomegaly is possible. In women, thrombosis can lead to habitual miscarriage.

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

Essential thrombocythemia should be suspected in patients with splenomegaly, as well as in individuals with complaints and symptoms characteristic of myeloproliferative disease, an increase in the number of platelets or impaired morphological structure. If essential thrombocythemia is suspected, a complete blood count, peripheral blood smear, myelogram, and cytogenetic analysis, including the definition of the Philadelphia chromosome or BCR-ABL, should be performed. The number of platelets may exceed 1,000,000 / µl, but may be lower (up to 500,000 / µl). Platelet count often spontaneously decreases during pregnancy. In peripheral blood smears are determined by platelet aggregates, giant Platelets and megakaryocytes fragments. In the bone marrow, megakaryocytic hyperplasia and a variety of newly formed platelets are detected. In the bone marrow reserves of iron remain. Unlike other myeloproliferative diseases, in which thrombocytosis is possible, normal hematocrit, MCV and iron content, as well as the absence of Philadelphia chromosome and translocation of BCR-ABL (present in chronic myelocytic leukemia), the absence of Erythrocyte ritolocyte-free cells, and the absence of Erythrocyte ritolocytes, are absent. (what is observed in idiopathic myelofibrosis). In addition, this diagnosis requires the exclusion of other pathological conditions in which secondary thrombocytosis may occur.

[17], [18], [19],

Differential diagnosis

Secondary thrombocytosis can develop in chronic inflammatory diseases, acute infections, bleeding, iron deficiency, hemolysis, or tumors. Platelet function is usually not impaired. However, in myeloproliferative diseases, platelet aggregation disorders are detected in 50% of patients. Unlike primary thrombocythemia, it does not increase the risk of thrombotic or hemorrhagic complications if patients have no arterial disease or prolonged immobilization. In secondary thrombocytosis, the platelet count is usually <1,000,000 / μl; The cause of this condition can sometimes be determined by taking anamnesis, during a physical examination, by X-ray or blood tests. Treatment of the underlying disease usually returns the platelet count to a normal level.

[20], [21], [22], [23], [24], [25],

Treatment of the essential thrombocythemia

There is no consensus when to begin therapy. In case of mild vasomotor symptoms (for example, headache, mild finger ischemia, erythromelalgia) and in order to reduce the risk of thrombosis in patients from the low-risk group, aspirin dosage in a dose of 81 mg x 1 time per day is enough. Since the prognosis of the disease is usually favorable, the use of potentially toxic therapy that reduces platelet levels should be limited. Patients with severe bleeding need therapy to reduce the number of platelets. Patients older than 60 years with a history of thrombosis or having a comorbidity that increases the risk of thrombosis should receive drugs that reduce the level of platelets. The question of the appointment of drugs that reduce the level of platelets in patients younger than 60 years without symptoms of the disease requires further study. Most pregnant women are prescribed aspirin.

Myelosuppressive platelet-lowering therapy usually includes anagrelide, hydroxyurea, or interferon a. The goal of therapy is to reduce the number of platelets <450 000 / µl without significant clinical toxicity or suppression of the remaining hemopoiesis sprouts. Since anagrelide and hydroxyurea penetrate the placenta, they are not used during pregnancy; interferon can be used in pregnant women.

Thrombocytophoresis can be used to quickly reduce the number of platelets (for example, in the case of severe bleeding or thrombosis; before 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 quick 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.

[26]