Low-Risk Essential Thrombocythemia: A Comprehensive Review

Abstract

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by a persistently elevated platelet count in the absence of a secondary cause. The clinical consequences of uncontrolled thrombocytosis can include both thrombosis and hemorrhage. Patients with features conferring a "high risk" of vascular events benefit from reduction of the platelet count through cytoreductive therapy. The management of patients who lack such high-risk features has until recently been less well defined, but it is now apparent that many require minimal or even no intervention. In this review, we discuss the diagnostic pathway for younger patients with unexplained thrombocytosis, including screening molecular investigations, the role of bone marrow biopsy, and investigations in those patients negative for the classic myeloproliferative neoplasm driver mutations (JAK2, CALR, MPL). We discuss conventional and novel risk stratification methods in essential thrombocythemia and how these can be best applied in clinical practice, particularly in the era of more comprehensive genomic testing. The treatment approach for "low risk" patients is discussed including antiplatelets and the options for cytoreductive therapy, if indicated, together with areas of clinical need for future study.

Figure 1.

Diagnostic pathway for essential thrombocythemia. BM = bone marrow; BMAT = bone marrow aspirate and trephine; CML = chronic myeloid leukemia; ET = essential thrombocythemia; MPN = myeloproliferative neoplasm.

Figure 2.

Bone marrow histology in triple-negative essential thrombocythemia and reactive thrombocytosis. A and B: A bone marrow trephine biopsy from a 30-y-old woman with an isolated thrombocytosis of 1300-1400 × 10⁹/L, no apparent secondary cause and no JAK2, CALR, or MPL mutation on standard screening assays. Histology shows a mildly hypercellular marrow, increased megakaryocytes with large, atypical forms and some clusters, in keeping with triple-negative essential thrombocythemia. C and D: A biopsy from a 35-y-old woman with an isolated thrombocytosis of 800-900 × 10⁹/L on a background of Crohn’s disease and rheumatoid arthritis, with negative molecular screening. Histology shows a mildly hypercellular marrow with minimal megakaryocyte hyperplasia and without proliferative morphology, in keeping with a reactive thrombocytosis.