Caramazza Domenica, Caracciolo Clementina, Barone Rita, Malato Alessandra, Saccullo Giorgia, Cigna Valeria, Berretta Salvatore, Schinocca Luciana, Quintini Gerlando, Abbadessa Vincenzo, Di Raimondo Francesco, Siragusa Sergio
Cattedra ed U.O. di Ematologia, Azienda Ospedaliera Universitaria Policlinico di Palermo, Via del Vespro 127, I-90127, Palermo, Italy.
Ann Hematol. 2009 Oct;88(10):967-71. doi: 10.1007/s00277-009-0706-x. Epub 2009 Feb 13.
The evidence that leukocytes may contribute to the pathogenesis of thrombosis in Chronic Myeloproliferative Neoplasms is increasing but not definitive. To further enforces whether an increased leukocyte count is associated with thrombosis and whether this effect can be modulated by cytoreductive therapy, we analyzed the clinical course of 187 patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) followed at two Italian Institutions over a period of 7 years. The association was measured at diagnosis or before thrombotic events: a multivariable analysis was carried out using data at baseline and time-dependent covariates. We found that white blood cells (WBC) count above 9.5 x 10(9)/L at diagnosis (baseline analysis) was associated with thrombosis during the follow-up (Hazard Ratio [HR] of 1.8, p 0.03). At the time-dependent analysis, therapy with hydroxyurea (HU), lowering by 35% the baseline WBC level, reduced such strength of association giving a HR of 1.3 (p value non significant). We found a trend between WBC level and thrombosis in untreated low-risk patients (RR of 1.9, 95% CI 0.9 to 3.1); in high-risk patients treated with HU this correlation was clearly lost (RR 1.1, 95% CI 0.2 to 2.7). Finally, we could not identify the presence of JAK2 (V617F) as a risk factor for thrombosis. Properly designed prospective studies should corroborate such results.
白细胞可能在慢性骨髓增殖性肿瘤的血栓形成发病机制中发挥作用，这方面的证据越来越多，但尚未明确。为了进一步证实白细胞计数升高是否与血栓形成有关，以及这种影响是否可通过细胞减灭治疗进行调节，我们分析了意大利两家机构随访7年的187例真性红细胞增多症（PV）和原发性血小板增多症（ET）患者的临床病程。在诊断时或血栓形成事件之前测量这种关联：使用基线数据和时间依赖性协变量进行多变量分析。我们发现，诊断时（基线分析）白细胞（WBC）计数高于9.5×10⁹/L与随访期间的血栓形成相关（风险比[HR]为1.8，p = 0.03）。在时间依赖性分析中，羟基脲（HU）治疗使基线WBC水平降低35%，降低了这种关联强度，HR为1.3（p值无统计学意义）。我们在未治疗的低风险患者中发现WBC水平与血栓形成之间存在趋势（相对风险[RR]为1.9，95%可信区间为0.9至3.1）；在接受HU治疗的高风险患者中，这种相关性明显消失（RR为1.1，95%可信区间为0.2至2.7）。最后，我们未能确定JAK2（V617F）的存在是血栓形成的危险因素。设计合理的前瞻性研究应证实这些结果。
