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Essential Thrombocytosis (ET) Diagnosis

The World Health Organization (WHO) has established these criteria for the diagnosis of ET.* These criteria help to differentiate ET from other myeloproliferative disorders:
  1. Sustained platelet count of at least 450 x 109/L.
  2. Bone marrow biopsy showing predominant proliferation of enlarged mature megakaryocytes; no significant increase of granulocytic or erythroid precursors. This finding distinguishes essential thrombocythemia from another entity with thrombocytosis, namely prefibrotic primary myelofibrosis, which is identified by increased granulocytic or erythroid precursors, atypical megakaryocytes, and increased bone marrow cellularity. Patients with prefibrotic primary myelofibrosis have a worse survival than patients with essential thrombocythemia because of an increased progression to myelofibrosis and increased progression to acute myelogenous leukemia. Patients with prefibrotic primary myelofibrosis may also have a higher tendency to bleed, which can be exacerbated by low-dose aspirin.
  3. Not meeting criteria for polycythemia vera (p. vera), primary myelofibrosis, chronic myelogenous leukemia, myelodysplastic syndrome, or other myeloid neoplasm.
  4. Demonstration of JAK2(V617F) mutation or myeloproliferative leukemia (MPL) exon 10 mutation. In the absence of a clonal marker, there must be no evidence for reactive thrombocytosis. In particular, with a decreased serum ferritin, there must be no increase in hemoglobin level to p. vera range with iron replacement therapy. In the presence of a JAK2(V617F) or MPL mutation and exclusion of other myeloproliferative or myelodysplastic features, a bone marrow aspirate/biopsy may not be mandatory for a diagnosis. About 60% of patients with essential thrombocythemia carry a JAK2(V617F) mutation, and about 5% to 10% of the patients have activating mutations in the thrombopoietin receptor gene, MPL. About 70% of the patients without JAK2(V617F) or MPL carry a somatic mutation of the calreticulin gene, which is associated with a more indolent clinical course than is seen with JAK2(V617F) or MPL mutations.

*Reference: Essential thrombocythemia. National Cancer Institute website. Available at: Accessed October 23, 2014.