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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2310-2313.
Prepublished online as a Blood First Edition Paper on November 16, 2006; DOI 10.1182/blood-2006-09-046342.
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Submitted September 8, 2006
Accepted October 30, 2006
Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors and Jak2 mutation status
Alessandra Carobbio, Guido Finazzi, Vittoria Guerini, Orietta Spinelli, Federica Delaini, Roberto Marchioli, Giovanna Borrelli, Alessandro Rambaldi, and Tiziano Barbui*
Divisione di Ematologia, Ospedali Riuniti Bergamo, Bergamo, Italy
Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
* Corresponding author; email: tbarbui{at}ospedaliriuniti.bergamo.it.
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 our Institution. 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: a) increased leukocyte count at diagnosis was associated with thrombosis during follow-up ("baseline analysis", RR 2.3, 95% CI 1.4-3.9, p=0.001); b) Hydroxyurea 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, n.s.), c) the association of leukocytosis and thrombosis was more evident in untreated low-risk patients (RR 2.7, 95% CI 1.2-6.4, p=0.01) as compared to HU-treated high-risk patients (RR 1.6, 95% CI 0.8-3.2, n.s.); d) 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 to validate these findings in prospective clinical studies.
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