Arterial (AT) and venous (VT) thrombotic events are the most common complications in patients with polycythemia vera (PV) and are the leading causes of morbidity and mortality. In this regard, the impact of JAK2V617F variant allele frequency (VAF) is still debated. The purpose of the current study was to analyze the impact of JAK2V617F VAF in the context of other established risk factors for thrombosis in a total of 865 2016 WHO-defined PV patients utilizing two independent cohorts: University of Florence (n = 576) as a training cohort and Policlinico Gemelli, Catholic University, Rome (n = 289) as a validation cohort. In the training cohort VT free-survival was significantly shorter in the presence of a JAK2V617F VAF > 50% (HR 4; p < 0.0001), whereas no difference was found for AT (HR 0.9; p = 0.8). Multivariable analysis identified JAK2V617F VAF > 50% (HR 3.8, p = 0.001) and previous VT (HR 2.2; p = 0.04) as independent risk factors for future VT whereas diabetes (HR 2.4; p = 0.02), hyperlipidemia (HR 2.3; p = 0.01) and previous AT (HR 2; p = 0.04) were independent risk factors for future AT. Similarly, JAK2V617F VAF > 50% (HR 2.4; p = 0.01) and previous VT (HR 2.8; p = 0.005) were confirmed as independent predictors of future VT in the validation cohort. Impact of JAK2V617F VAF > 50% on VT was particularly significant in conventional low-risk patients, both in Florence (HR 10.6, p = 0.005) and Rome cohort (HR 4; p = 0.02). In conclusion, we identified JAK2V617F VAF > 50% as an independent strong predictor of VT, supporting that AT and VT are different entities which might require distinct management.

动脉 (AT) 和静脉 (VT) 血栓事件是真性红细胞增多症 (PV) 患者最常见的并发症，并且是发病率和死亡率的主要原因。在这方面，JAK2 V617F变异等位基因频率（VAF）的影响仍然存在争议。本研究的目的是分析JAK2 V617F VAF 在其他已确定的血栓形成危险因素背景下的影响，共有 865 名 2016 年 WHO 定义的 PV 患者使用两个独立队列：佛罗伦萨大学 ( n  = 576) 作为一个训练队列和罗马天主教大学的 Policlinico Gemelli ( n  = 289) 作为验证队列。在训练队列中，在存在JAK2的情况下，VT 自由生存时间明显缩短V617F VAF > 50% (HR 4; p  < 0.0001)，而 AT 没有发现差异 (HR 0.9; p  = 0.8)。多变量分析确定JAK2 V617F VAF > 50% (HR 3.8, p  = 0.001) 和既往 VT (HR 2.2; p  = 0.04) 是未来 VT 的独立危险因素，而糖尿病 (HR 2.4; p  = 0.02)、高脂血症 (HR 2.3 ; p  = 0.01) 和以前的 AT (HR 2; p  = 0.04) 是未来 AT 的独立危险因素。同样，JAK2 V617F VAF > 50% (HR 2.4; p  = 0.01) 和之前的 VT (HR 2.8; p = 0.005）在验证队列中被确认为未来 VT 的独立预测因子。JAK2 V617F VAF > 50% 对 VT 的影响在佛罗伦萨（HR 10.6， p  = 0.005）和罗马队列（HR 4；p  = 0.02）的传统低风险患者中尤为显着。总之，我们将JAK2 V617F VAF > 50% 确定为 VT 的独立强预测因子，支持 AT 和 VT 是可能需要不同管理的不同实体。