(Essential thrombocytosis, primary thrombocythemia)
The essential thrombocythemia (ET) is characterized by increased platelet counts, hyperplastic megakaryocytes and a tendency to bleeding or thrombosis. Her symptoms and clinical signs include performance weakness, headache, paresthesia, bleeding, splenomegaly and erythromelalgia with digital ischemia. Diagnosis is based on platelet count> 450,000 / ul normal erythrocyte, hematocrit and iron stores values. In addition, myelofibrosis, Philadelphia chromosome (or translocation of BCR-ABL) or others must be excluded thrombocytosis causing diseases. The therapy is not unified, but may include the administration of acetylsalicylic acid. In patients> 60 years old and those with previous thrombosis and transient ischemic attacks should be given to the reduction of platelet count cytostatics. The available data suggests that the risk of thrombosis does not correlate with the platelet count but the number of leukocytes.
The essential thrombocythemia (ET) is characterized by increased platelet counts, hyperplastic megakaryocytes and a tendency to bleeding or thrombosis. Her symptoms and clinical signs include performance weakness, headache, paresthesia, bleeding, splenomegaly and erythromelalgia with digital ischemia. Diagnosis is based on platelet count> 450,000 / ul normal erythrocyte, hematocrit and iron stores values. In addition, myelofibrosis, Philadelphia chromosome (or translocation of BCR-ABL) or others must be excluded thrombocytosis causing diseases. The therapy is not unified, but may include the administration of acetylsalicylic acid. In patients> 60 years old and those with previous thrombosis and transient ischemic attacks should be given to the reduction of platelet count cytostatics. The available data suggests that the risk of thrombosis does not correlate with the platelet count but the number of leukocytes. Pathophysiology The essential thrombocythemia is a clonal variation of a multipotent hematopoietic stem cell. Nevertheless, some women in whom the diagnostic criteria for essential thrombocythemia are met polyclonal hematopoiesis. The essential thrombocythemia occurs usually with a peak incidence between the ages of 50 and 70 years of age and a second in young women. The platelet production is increased. The life of platelets is usually normal, but may be shortened by increased splenic sequestration, or in patients with digital erythromelalgia ischemia. Thrombocytosis can result in severe bleeding or even more frequently to thrombosis. Thrombosis is the ultimate cause of increased morbidity and mortality. Recent studies show that increased white blood cell count is an important independent risk factor for the development of thrombosis. Although it is reported in isolated cases (and intuitively assumed) that increased platelet count can increase the risk of thrombosis, but found an inverse relationship between absolute platelet count and the risk of thrombosis in a study. Bleeding occurs in extreme thrombocytosis (> 1,500,000 platelets / ul) due to an acquired deficiency of von Willebrand factor in common. Symptoms and complaints Common symptoms include weakness hematoma and bleeding gout Ocular migraines paresthesias of the hands and feet thrombosis and thromboembolic events clots can cause symptoms in the affected area (eg. As neurological deficits with stroke or transient ischemic attack, pain and / or swelling in the leg thrombosis of the lower extremity, chest pain and shortness of breath with pulmonary embolism). Most is light bleeding in the form of nosebleeds, easy bruising or gastrointestinal bleeding. A erythromelalgia (burning pain in hands and feet with heat sensation, redness and sometimes digital ischemia) may occur. Splenomegaly (usually not palpable> 3 cm below the left costal margin) occurs in <50% of patients. In rare cases, hepatomegaly may occur. Thrombosis can lead to repeated spontaneous abortions. Diagnostic blood count and peripheral blood smear exclusion of the causes of secondary Thrombocythemie Cytogenetic and molecular genetic studies. Mutationsalanalyse of JAK2, CALR and MPL. Mutation of JAK2 by KCV Maybe bone marrow examination ET is a diagnosis of exclusion, and for patients who have frequent reactive causes (Reactive thrombocytosis (secondary thrombocythemia)) were excluded, should be considered. On suspicion of this disease should have a complete blood count, peripheral blood smear and cytogenetic studies, including Philadelphia chromosome or BCR-ABL test and mutation analysis of JAK2, CALR and MPL are performed. Some experts recommend a bone marrow examination, particularly in patients with anemia, macrocytosis, leukopenia or evidence of extramedullary hematopoiesis (z. B. enlarged liver and / or spleen, or other soft tissue infiltration). However, although the classic essential thrombocythemia morphological abnormalities have been described, the diagnostic value of a bone marrow examination is not assured. Most are platelet counts> 1000000 / ul, but there are also present values ??of only up to 450,000 / ul. During pregnancy, the platelet count may decrease spontaneously. In peripheral blood smear is platelet aggregates, giant platelets and Megakaryozytenfragmente find. The bone marrow is a proliferation of megakaryocytes, which form a large amount of platelets. The iron stain in the bone marrow falls mostly positive. To make a distinction from other myeloproliferative diseases that also cause thrombocytosis, a normal hematocrit, MCV and normal iron levels are necessary for the diagnosis of thrombocythemia essential. Undetectable are Philadelphia chromosome, BCR-ABL translocation and teardrop-erythrocytes (Dakryozyten); it may, however, a significant increase in bone marrow fibrosis is present (present in the primary myelofibrosis). The JAK2V617F mutation occurs in approximately 50% of patients; provided that it is present, it helps to distinguish the essential thrombocythemia from other causes of Thrombocythemie. A small minority of patients with essential thrombocythemia have acquired somatic thrombopoietin receptor gene mutations (c-mpl). Some other patients have mutations in exon 9 of calreticulin gene. Prognosis Life expectancy is almost normal. Although often symptoms occur, the disease often takes a benign course. Severe arterial and venous thrombotic complications are rare but can be life threatening. A leukemic transformation occurs at <2% of patients, but this rate can after treatment with cytostatic agents, in particular alkylating agents, increase. Therapy acetylsalicylic acid medicines that reduce platelet count (z. B. hydroxyurea, anagrelide) Rare plateletpheresis rare cytostatics rare interferon rare stem cell transplantation In mild vasomotor symptoms (eg. As headaches, lightweight digital ischaemia, erythromelalgia) and to reduce the risk of thrombosis at low risk patients can acetylsalicylic acid (100 mg orally once daily) are sufficient. Also received the most pregnant patients aspirin. The gift in low-risk patients is acceptable, but not backed by studies. Since the prognosis is usually good, potentially toxic drugs should be used sparingly to reduce platelet count. Approved Indications for such therapy are Past thrombosis or transient ischemic attack aged> 60 years Further indications are controversial. Patients with severe bleeding or extreme thrombocytosis (high risk patients) may require therapy to lower the platelet count. It is unclear whether asymptomatic patients should take <60 years Arzeimittel to reduce platelet count. To the myelosuppressive, the platelet count lowering drugs include hydroxyurea, interferon alpha-2b and anagrelide (sometimes in combination with low-dose acetylsalicylic acid). Hydroxyurea is considered the drug of choice, especially if elevated white blood cell counts should be normalized. However, some doctors prefer with isolated thrombocytosis anagrelide. Interferon alpha-2b can be used if necessary for the treatment of pregnant women. Since anagrelide and hydroxyurea cross the placental barrier, it should not be used during pregnancy. Dosage and monitoring of Hydroxurea are described in the section for the treatment of polycythemia vera (polycythemia vera). The goal of therapy is to achieve a platelet count <450,000 / ul without significant clinical toxicity or myelosuppression. Some experts recommend a lower platelet count. The distance from platelets (Plateletpherese) was used in rare cases of severe bleeding, recurrent thrombosis or before emergency surgery as therapeutic measure for the rapid reduction of platelet counts. Due to the long average life of platelets (7 days) have Hydroxyurea and anagrelide no direct effect. Allogeneic stem cell transplantation (hematopoietic stem cell transplantation) is rarely used in essential thrombocythemia but can be effective in younger patients when other treatments fail and there is a good donor available. Key points The essential thrombocythemia is usually the clonal variation of a multipotent hematopoietic stem cell, which results in increased platelet count. The patients have an increased risk of thrombosis, and to a lesser extent of bleeding. The essential thrombocythemia is a diagnosis of exclusion; in particular, other myeloproliferative disorders and a reactive (secondary) thrombocytosis must be excluded. The treatment of most patients is done with aspirin. Other treatments are controversial, but high-risk patients (eg. As those> 60 years, with significant bleeding, recurrent thrombosis, extreme thrombocytosis) can benefit from a more aggressive treatment with myelosuppressive drugs, interferon alfa-2b and Plateletpherese benefit.