ET is a myeloproliferative disorder (also includes polycythemia vera, idiopathic myelofibrosis, and chronic myelogenous leukemia) that manifests as an increased platelet count (usually greater than 1,000,000 cells/mL), megakaryocytic hyperplasia (noted on bone marrow biopsy) and a thrombotic or hemorrhagic predisposition. Patients who have suffered a previous thrombotic episode or have an age greater than 60 years are considered higher risk for thrombotic complications; whereas, patients with extreme thrombocytosis are at an increased risk for hemorrhagic complications. Young patients with platelet counts less than 1.5 million are generally free from hemorrhage or thrombosis and require no therapy only close follow-up. This disease usually manifests during the fifth or sixth decade of life with an equal occurrence in male or female patients. One criterion for the diagnosis of ET established by the Polycythemia Vera Study Group is a platelet count greater than 600,000 cells/microL. However, a platelet count elevation of this degree does not establish the diagnosis of ET because several disorders associated with thrombocytosis may yield similar platelet counts. Disorders associated with significant secondary thrombocytosis include iron deficiency anemia, chronic inflammatory disorders, chronic infections, postsplenectomy, carcinomas, hemolytic states, and acute blood loss. Also, other myeloproliferative disorders such as polycythemia vera (PCV), chronic myelogenous leukemia (CML), or myelofibrosis may provoke similar platelet counts.

Symptoms include weakness, hemorrhaging, headache, dizziness, or paresthesias. Usually, bleeding is mild and manifests as epistaxis, gastrointestinal bleeding, or ecchymosis. Splenomegaly is noted on physical exam in approximately 60% of patients with this disorder. Thrombotic complications may include digital ischemia with or without erythromelalgia (intense asymmetric erythema with burning or throbbing pain randomly distributed in the plantar and palmar areas of the feet and hands) or pulmonary embolism or deep vein thrombosis to include Budd-Chiari syndrome and portal-vein thrombosis. Laboratory abnormalities include platelet counts greater than 600,000 cells/mL with associated platelet aggregates, giant platelets, and megakaryocyte fragments discovered on bone marrow examination. Bone marrow studies in these patients also show normal iron stores and an increased reticulin content or megakaryocyte clusters and lack evidence of marrow fibrosis. There is often, in approximately 50% of patients, an associated leukocytosis but this rarely exceeds 40,000 cells/microL. Elevations in the serum B12, uric acid and leukocyte alkaline phosphatase (LAP) levels are commonly associated with this disorder, and pseudohyperkalemia may result from the excessive platelet levels. PCV and CML may be eliminated from the differential diagnosis by a normal RBC mass and the absence of the Philadelphia chromosome, respectively. Approximately 50% of patients display the Janus Kinase 2 (JAK-2) mutation, and a positive peripheral blood sample for this mutation eliminates the need for bone marrow biopsy to establish the diagnosis.

Criteria for the diagnosis of essential thrombocythemia include a persistent platelet elevation above 600,000 cells/microL but often greater than 1,000,000 cells/microL, megakaryocytic hyperplasia noted on bone marrow examination, an absence of other myeloproliferative diseases, and an absence of any underlying conditions known to cause secondary reactive thrombocytosis (chronic infections, chronic inflammatory disorders, iron deficiency, malignancy, or prior splenectomy). As stated above the presence of the JAK-2 mutation is indicative of the diagnosis.

Patients with this disorder can usually expect a normal life span; however, they do experience a higher risk of thrombotic or hemorrhagic complications. Therapy must be individualized to each specific patient. Patients with a history of thrombosis warrant treatment as do patients with cardiac risk factors and those with platelet counts in excess of 600,000 cells/microL. Patients with platelet counts lower than 600,000 cells/microL and no risk factors or thrombotic history may be observed, as thrombotic complications are rare when platelets are not in excess of 600,000 cells/microL. Therapy is generally instituted with hydroxyurea (plus low dose aspirin when thrombotic complications are anticipated) when treatment is deemed necessary. If hydroxyurea is ineffective, treatment with alpha interferon may be a consideration. Once therapy with hydroxyurea is instituted, monitor patients closely for progression to myelofibrosis or acute myelogenous leukemia.