Clonal hemapoiesis and risk of thrombosis in young female patients with essential thrombocythemia

Objective. Several studies demonstrated a high prevalence of nonrandom X-ch romosome inactivation pattern (X-CIP) in essential thrombocythemia (ET), Th is study explored the incidence of clonal hemopoiesis in myeloid precursors and endogenous erythroid colonies (EECs) in ET patients and its correlatio n with thrombotic manifestations. Materials and Methods. Clonal analysis of hemopoiesis using X-CIP was perfo rmed in 40 female patients with ET. Median age was 40.5 years (range 20-64) , and median platelet count at testing time was 700 x 10(9)/L (range 220-13 00 x 10(9)/L). Patients older than 65 years were excluded to reduce age-rel ated skewing. Clonality was assessed on neutrophils, platelets, EECs, and b one marrow CD34(+) cells. Results, Eight (20%) of 40 patients developed thrombosis mainly at diagnosi s, Clonal hemopoiesis was found in 17 (42.5%) patients, 15 (37.5%) had poly clonal hemopoiesis, and g (20%) were considered uninterpretable due to cons titutive skewing, Clonality was confirmed on purified CD34(+) subpopulation s from bone marrow, documenting that clonality does not appear lineage-rest ricted. There were no statistical differences in age at diagnosis, median p latelet count at testing time, and length of follow-up, Thrombotic episodes were significantly more frequent in the monoclonal group (p = 0.04, Fisher exact test). Conclusions. Young female patients with ET exhibiting a clonal pattern of h emopoiesis by X-CIP analysis are at higher risk for thrombosis. X-CIP analy sis may contribute to defining the individual risk leading to appropriate t reatment, X-CTP will allow a correct diagnosis in patients with latent myel oproliferative disorders and thrombosis in unusual sites, Clonal hemopoiesi s is easily recognized by X-CLP, but its applicability is limited to the fe male sex and is hampered by the presence of age-related or constitutive ske wing. (C) 2001 International Society for Experimental Hematology, Published by Elsevier Science Inc.