We applied a parametric Markov five-state model, on a well-characterized international cohort of 1,545 patients with polycythemia vera (PV; median age 61 years; females 51%), in order to examine the impact of incident thrombosis on the trajectory of death or disease progression. At a median follow-up of 6.9 years, 347 (23%) deaths, 50 (3%) blast phase (BP), and 138 (9%) fibrotic (post-PV MF) transformations were recorded. Incident thrombosis occurred at a rate of 2.62% pt/yr (arterial 1.59% and venous 1.05%). The probability of death, in the first 10 years, for 280 (18%) patients who developed thrombosis during follow-up was 40%, which was two-fold higher than that seen in the absence of thrombosis or any other transition state (20%; p < 0.01); the adverse impact from thrombosis was more apparent for arterial (HR 1.74; p < 0.01) vs venous thrombosis (p=NS) and was independent of other fixed (i.e., age, prior venous thrombosis, leukocytosis) or time-dependent (i.e., progression to BP or MF) risk variables. The transition probability to post-PV MF increased over time, in a linear fashion, with a rate of 5% capped at 5 and 10 years, in patients with or without incident thrombosis, respectively. The impact of thrombosis on transition probability to death or post-PV MF tapered off beyond 10 years and appeared to reverse direction of impact on MF evolution at the 12-year time point. These observations suggest thrombosis in PV to be a marker of aggressive disease biology or a disease-associated inflammatory state that is consequential to both thrombosis and disease progression.
我们采用参数化马尔可夫五状态模型，对一个包含1,545例特征明确的真性红细胞增多症患者（中位年龄61岁；女性占51%）的国际队列进行分析，旨在探究新发血栓事件对死亡或疾病进展轨迹的影响。在中位随访6.9年期间，共记录到347例（23%）死亡、50例（3%）急变期转化及138例（9%）纤维化（真性红细胞增多症后骨髓纤维化）转化。新发血栓事件发生率为2.62%患者/年（动脉血栓1.59%，静脉血栓1.05%）。在随访期间发生血栓的280例（18%）患者中，前10年的死亡概率为40%，较未发生血栓或其他过渡状态的患者（20%；p < 0.01）升高两倍；动脉血栓（风险比1.74；p < 0.01）的不良影响相较于静脉血栓（p=无统计学意义）更为显著，且独立于其他固定风险因素（如年龄、既往静脉血栓史、白细胞增多）或时间依赖性风险变量（如进展至急变期或骨髓纤维化）。无论是否发生血栓事件，患者进展至真性红细胞增多症后骨髓纤维化的转移概率均随时间呈线性增长，第5年和第10年的上限增长率分别为5%。血栓对死亡或进展至真性红细胞增多症后骨髓纤维化转移概率的影响在10年后逐渐减弱，并在第12年时间点对骨髓纤维化进展的影响呈现反向趋势。这些观察结果表明，真性红细胞增多症中的血栓事件可能是侵袭性疾病生物学特征或疾病相关炎症状态的标志，这种状态同时影响血栓形成和疾病进展。
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