title: Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status.
abstract: Leukocytes contribute to the pathogenesis of thrombosis in essential thrombocythemia (ET) through recently discovered mechanisms of activation and interaction with platelets and endothelial cells. To evaluate whether an increased leukocyte count was associated with thrombosis and whether this effect can be modulated by therapy, we analyzed the clinical course of 439 patients with ET followed at the Ospedali Riuniti di Bergamo. The strength of the association was measured at diagnosis or before thrombotic events by multivariable analyses carried out using data at baseline as well as time-varying covariates. The results showed that (1) an increased leukocyte count at diagnosis was associated with thrombosis during follow-up ("baseline analysis," relative risk [RR] 2.3, 95% confidence interval [CI] 1.4-3.9, P = .001); (2) hydroxyurea (HU) lowered leukocytosis and reduced the strength of the association between leukocytosis and thrombosis ("time-dependent analysis," RR 1.6, 95% CI 0.9-2.0, not significant [NS]); (3) the association of leukocytosis and thrombosis was more evident in untreated low-risk patients (RR 2.7, 95% CI 1.2-6.4, P = .01) compared with HU-treated high-risk patients (RR 1.6, 95% CI 0.8-3.2, NS); and (4) the presence of JAK2 V617F was not identified as a risk factor for thrombosis during follow-up despite a significant association between the mutation and leukocytosis. We suggest validation of these findings in prospective clinical studies.
authors.affiliation: Divisione di Ematologia, Ospedali Riuniti di Bergamo, Bergamo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carobbio
authors.forename: Guido
authors.initials: G
authors.lastname: Finazzi
authors.forename: Vittoria
authors.initials: V
authors.lastname: Guerini
authors.forename: Orietta
authors.initials: O
authors.lastname: Spinelli
authors.forename: Federica
authors.initials: F
authors.lastname: Delaini
authors.forename: Roberto
authors.initials: R
authors.lastname: Marchioli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Borrelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D007964:Leukocytosis / Q000150:complications / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000150:complications* / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D013927:Thrombosis / Q000150:complications* / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics
chemical_list: D053614:Janus Kinase 2