Dipartimento di Ematologia, Servizio di Prevenzione e Cura Sindromi Emorragiche e Trombotiche, Ospedale Civile dello Spirito Santo, Pescara, Italy.
Blood Transfus. 2010 Jan;8(1):21-7. doi: 10.2450/2009.0004-09.
JAK2(V617F) mutation has been recognized as a possible thrombotic risk factor in essential thrombocythaemia (ET). It's role is probably due to an increased myeloid proliferation and white blood cells (WBC) activation. Only few data are available about the effect of JAK2(V617F) on hemorrhagic risk. The aim of our study was to evaluate the influence of the mutational status on hemorrhagic complication.
We retrospectively analysed laboratory and clinical findings of 106 consecutive patients with ET to evaluate possible relationships between thrombosis, abnormal bleeding, peripheral blood count, overexpression of PRV1 and JAK2(V617F) mutational status.
ON UNIVARIATE ANALYSIS WE FOUND: an association between JAK2(V617F) mutation and thrombotic events before or at diagnosis (p<0.003, OR=4.44, 95% CI=1.74-12.4); no statistical correlation between the median value of JAK2(V617F) burden and an increased risk of thrombosis (p=0.4, 95% CI= -22.8-10.4); significant relationships between mutated status and higher haematocrit, high WBC count and low platelet count; and a strong correlation between JAK2(V617F) and PRV1 overexpression (p<0.0001). Moreover, the presence of the JAK2(V617F) mutation and a WBC count greater than 8.4 x 10(9)/L were found to be independent factors related to thrombotic complications in multivariable analysis (p<0.006, OR=3.85, 95% CI=1.3-11.9; and p<0.002, OR=2.8, 95% CI=1.08-7.03, respectively). The prognostic impact of JAK2 mutation status and WBC count on thrombosis was evaluated in the whole cohort. Only new cases occurring in patients without previous thrombotic events were recorded for the analysis. The multivariable analysis showed a statistical correlation between the presence of the mutation and a WBC count greater than 8.12 x 10(6)/L and an increased risk of thrombosis if no cytoreductive treatment was started at diagnosis (JAK2(V617F) p=0.02; WBC p=0.02; OR=4.97; 95% CI=1.04-23.8). Finally, wild-type JAK2 was associated with a higher haemorrhagic risk (p=0.02) in univariate analysis but only a platelet count greater than 1,022 x 10(9)/L was associated with an increased risk of bleeding in the multivariable analysis.
Our data confirm the role of both JAK2(V617F) as factor associated with an increased risk of thrombosis at the diagnosis and during follow-up in no treated patients. Moreover a WBC count over 8.4 x 10(9)/L1 was also strictly associated to an increased risk of thrombosis. Regarding bleedings, our statistical analysis allows to exclude the mutation protective role on haemorrhage.
JAK2(V617F) 突变已被认为是原发性血小板增多症 (ET) 中可能的血栓形成危险因素。它的作用可能是由于髓样细胞增殖和白细胞 (WBC) 激活增加。关于 JAK2(V617F) 对出血风险的影响，只有少数数据可用。我们的研究目的是评估突变状态对出血并发症的影响。
我们回顾性分析了 106 例连续 ET 患者的实验室和临床资料，以评估血栓形成、异常出血、外周血计数、PRV1 过表达与 JAK2(V617F) 突变状态之间的可能关系。
在单变量分析中，我们发现：JAK2(V617F) 突变与诊断前或诊断时的血栓形成事件之间存在关联（p<0.003，OR=4.44，95%CI=1.74-12.4）；JAK2(V617F) 突变负荷的中位数与血栓形成风险增加之间无统计学相关性（p=0.4，95%CI=-22.8-10.4）；突变状态与较高的血细胞比容、较高的白细胞计数和较低的血小板计数之间存在显著关系；JAK2(V617F) 与 PRV1 过表达之间存在强相关性（p<0.0001）。此外，多变量分析发现 JAK2(V617F) 突变和白细胞计数大于 8.4 x 10(9)/L 是血栓形成并发症的独立相关因素（p<0.006，OR=3.85，95%CI=1.3-11.9；p<0.002，OR=2.8，95%CI=1.08-7.03）。在整个队列中评估了 JAK2 突变状态和白细胞计数对血栓形成的预后影响。仅记录了在没有先前血栓形成事件的患者中新发生的病例进行分析。多变量分析显示，在未开始细胞减少治疗的情况下，突变的存在和白细胞计数大于 8.12 x 10(6)/L 与血栓形成风险增加之间存在统计学相关性（JAK2(V617F) p=0.02；白细胞计数 p=0.02；OR=4.97；95%CI=1.04-23.8）。最后，野生型 JAK2 在单变量分析中与较高的出血风险相关（p=0.02），但只有血小板计数大于 1022 x 10(9)/L 与出血风险增加相关在多变量分析中。
我们的数据证实了 JAK2(V617F) 既是诊断时和未治疗患者随访期间血栓形成风险增加的相关因素。此外，白细胞计数大于 8.4 x 10(9)/L1 也与血栓形成风险增加密切相关。关于出血，我们的统计分析排除了突变对出血的保护作用。
