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Essential
thrombocythemia is characterized by an increased platelet count,
megakaryocytic hyperplasia, and a hemorrhagic or thrombotic tendency. Symptoms
and signs may include weakness, headaches, paresthesias, bleeding,
splenomegaly, and digital ischemia. Diagnosis is based on a platelet count > 500,000/μL,
normal RBC mass or normal Hct in the presence of adequate iron stores,
and absence of myelofibrosis, the Philadelphia chromosome (or ABL-BCR rearrangement)
and any other disorder that could cause thrombocytosis. Treatment
is controversial but may include aspirin 81 mg/day po. Patients > 60 yr and those with multiple
comorbidities require cytotoxic drugs to lower platelet counts.
Etiology
and Pathophysiology
Essential thrombocythemia (ET) is a typically clonal abnormality of a multipotent hematopoietic stem cell. However, some women who fulfill diagnostic criteria for ET have polyclonal hematopoiesis. ET usually occurs between ages 50 and 70 yr.
Platelet production is increased. Platelet survival is usually normal, although it may decrease due to splenic sequestration. In elderly patients with atherosclerosis, increased platelets may lead to serious bleeding or, more commonly, thrombosis. Bleeding is more likely with extreme thrombocytosis, ie, > 1.5 million platelets/μL, due to an acquired von Willebrand's deficiency.
Symptoms,
Signs, and Diagnosis
The most common symptoms are weakness, hemorrhage, nonspecific headache, and paresthesias of the hands and feet. Bleeding is usually mild and manifests as epistaxis, easy bruisability, or GI bleeding. Digital ischemia may occur, and splenomegaly (usually not extending > 3 cm below the left costal margin) occurs in 60% of patients. Hepatomegaly may also occur. In pregnant patients, thrombosis may cause recurrent spontaneous abortions.
Although symptoms are common, the course of the disease is generally benign. Serious complications are rare but can be life-threatening.
ET should be considered in patients with splenomegaly and in those who have symptoms and signs of a myeloproliferative disorder, elevated platelet counts, or abnormal platelet morphologies. If the disease is suspected, CBC, peripheral smear, bone marrow examination, and cytogenetics, including Philadelphia chromosome or ABL-BCR assay, should be obtained. The platelet count can be > 1,000,000/μL but may be as low as 500,000/μL. Platelet counts often decrease spontaneously during pregnancy. The peripheral smear may show platelet aggregates, giant platelets, and megakaryocyte fragments. The bone marrow shows megakaryocytic hyperplasia, with an abundance of platelets being released. Marrow iron is present. To distinguish from other myeloproliferative disorders that produce thrombocytosis, the diagnosis of ET requires a normal Hct, MCV, and iron studies; absence of the Philadelphia chromosome and ABL-BCR translocation (present in chronic myelocytic leukemia); and absence of teardrop-shaped RBCs and significant increase in bone marrow fibrosis (present in idiopathic myelofibrosis). Diagnosis also requires exclusion of any clinically suspected disorders that can cause secondary thrombocytosis (see Table 2: Myeloproliferative Disorders: Causes of Thrombocytosis ).
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Table 2
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Causes of
Thrombocytosis
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Chronic inflammatory disorders: RA, inflammatory bowel disease, TB, sarcoidosis, Wegener's granulomatosis
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Acute infection
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Hemorrhage
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Iron deficiency
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Hemolysis
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Tumors: Cancer, Hodgkin lymphoma (Hodgkin's disease), non-Hodgkin lymphoma
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Surgery: Splenectomy
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Myeloproliferative and hematologic disorders: Polycythemia vera, chronic myelocytic leukemia, sideroblastic anemia, myelodysplasia (5q- syndrome), idiopathic myelodysplasia
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Prognosis
and Treatment
Life expectancy is near normal. Leukemic transformation occurs in < 2% of patients but may increase after exposure to cytotoxic therapy, especially alkylating agents.
Indications for therapy are controversial. For mild vasomotor symptoms (eg, headache, mild digital ischemia, erythromelalgia) and to decrease the risk of thrombosis in low-risk patients, aspirin 81 mg po once/day may be sufficient. Because the prognosis is often good, potentially toxic therapies that lower the platelet count should be used sparingly. Patients with significant bleeding need therapy to lower the platelet count. Patients > 60 yr with a previous thrombosis or with a comorbid condition that increases the risk of thrombosis should receive platelet-lowering drugs. Whether patients < 60 yr who are asymptomatic need platelet-lowering drugs needs to be studied. Most pregnant patients are given aspirin .
Myelosuppressive therapy to lower the platelet count usually consists of anagrelide , hydroxyurea , or interferon-α. The dosage and monitoring are described in the treatment of polycythemia vera (see below). The aim of therapy is a platelet count < 450,000/μL without significant clinical toxicity or suppression of other marrow elements. Because anagrelide and hydroxyurea cross the placenta, they are not used during pregnancy; interferon can be used in pregnant women.
For immediate reduction in the platelet count, plateletpheresis has been used (eg, in serious hemorrhage or thrombosis; before an emergency operation); this procedure, however, is rarely necessary. Due to the long half-life of platelets (7 days), hydroxyurea and anagrelide do not provide an immediate effect.
Thrombocytosis
(Secondary Thrombocythemia)
Thrombocytosis can develop secondary to chronic inflammatory disorders, acute infection, hemorrhage, iron deficiency, hemolysis, or tumors (see Table 2: Myeloproliferative Disorders: Causes of Thrombocytosis). Platelet function is usually normal. However, in myeloproliferative disorders, abnormalities of platelet aggregation occur in about 50% of patients. Unlike ET, thrombocytosis does not increase the risk of thrombotic or hemorrhagic complications unless patients have severe arterial disease or prolonged immobility. With secondary thrombocytosis, the platelet count is usually < 1,000,000/μL, and the cause may be obvious from the history, physical examination, or radiologic or blood testing. Treatment of the underlying disorder usually returns the platelet count to normal.
Last full review/revision November 2005
Content last modified November 2005
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