Disease Overview for Essential Thrombocythemia (ET)

Sustained platelet count of at least 450 × 109/L.

Bone marrow biopsy showing predominant proliferation of enlarged mature megakaryocytes; no significant increase of granulocytic or erythroid precursors. This finding distinguishes ET from another entity with thrombocytosis, namely prefibrotic primary myelofibrosis (PMF), which is identified by increased granulocytic or erythroid precursors, atypical megakaryocytes, and increased bone marrow cellularity. Patients with prefibrotic PMF have a worse survival than patients with ET because of an increased progression to myelofibrosis or acute myeloid leukemia.[2-4] Patients with prefibrotic PMF may also have a higher tendency to bleed, which can be exacerbated by low-dose aspirin.[5]

Not meeting criteria for polycythemia vera (PV), PMF, chronic myeloid leukemia, myelodysplastic syndrome, or other myeloid neoplasm.

Demonstration of a JAK2 V617F variant or an MPL exon 10 variant.[6] 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 PV range with iron replacement therapy. If a JAK2 variant or an MPL variant is present and other myeloproliferative or myelodysplastic features are excluded, a bone marrow aspirate/biopsy may not be mandatory for diagnosis.[7] About 60% of patients with ET carry a JAK2 variant, and about 5% to 10% of the patients have activating variants in the MPL thrombopoietin receptor gene. About 70% of patients without JAK2 or MPL variants carry a somatic variant in the CALR gene, which is associated with a more indolent clinical course than that seen in patients with JAK2 or MPL variants.[8-12]