Posch Florian, Riedl Julia, Reitter Eva-Maria, Kaider Alexandra, Zielinski Christoph, Pabinger Ingrid, Ay Cihan
Dr. Cihan Ay, Medical University of Vienna, Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Währinger Gürtel 18-20, 1090 Vienna, Austria, Tel.: +43 1 40400 4410, Fax: +43 1 40400 4030, E-mail:
Thromb Haemost. 2016 Apr;115(4):817-26. doi: 10.1160/TH15-09-0758. Epub 2016 Jan 7.
Venous thromboembolism (VTE) is a frequent complication of malignancy. The aim of this study was to investigate whether multi-state modelling may be a useful quantitative approach to dissect the complex epidemiological relationship between hypercoagulability, VTE, and death in cancer patients. We implemented a three-state/three-transition unidirectional illness-death model of cancer-associated VTE in data of 1,685 cancer patients included in a prospective cohort study, the Vienna Cancer and Thrombosis Study (CATS). During the two-year follow-up period, 145 (8.6 %) patients developed VTE, 79 (54.5 %) died after developing VTE, and 647 (38.4 %) died without developing VTE, respectively. VTE events during follow-up were associated with a three-fold increase in the risk of death (Transition Hazard ratio (HR)=2.98, 95 % confidence interval [CI]: 2.36-3.77, p< 0.001). This observation was independent of cancer stage. VTE events that occurred later during follow-up exerted a stronger impact on the risk of death than VTE events that occurred at earlier time points (HR for VTE occurrence one year after baseline vs at baseline=2.30, 95 % CI: 1.28-4.15, p=0.005). Elevated baseline D-dimer levels emerged as a VTE-independent risk factor for mortality (HR=1.07, 95 % CI: 1.05-1.08, p< 0.001), and also predicted mortality risk in patients who developed VTE. A higher Khorana Score predicted both the risk for VTE and death, but did not predict mortality after cancer-associated VTE. In conclusion, multi-state modeling represents a very potent approach to time-to-VTE cohort data in the cancer population, and should be used for both observational and interventional studies on cancer-associated VTE.
静脉血栓栓塞症（VTE）是恶性肿瘤常见的并发症。本研究旨在探讨多状态建模是否可能是一种有用的定量方法，以剖析癌症患者高凝状态、VTE和死亡之间复杂的流行病学关系。我们在一项前瞻性队列研究——维也纳癌症与血栓形成研究（CATS）纳入的1685例癌症患者的数据中，实施了癌症相关VTE的三状态/三转变单向疾病-死亡模型。在两年的随访期内，分别有145例（8.6%）患者发生VTE，79例（54.5%）在发生VTE后死亡，647例（38.4%）未发生VTE而死亡。随访期间的VTE事件与死亡风险增加三倍相关（转变风险比（HR）=2.98，95%置信区间[CI]：2.36-3.77，p<0.001）。这一观察结果与癌症分期无关。随访后期发生的VTE事件对死亡风险的影响比早期发生的VTE事件更强（基线后一年发生VTE与基线时发生VTE的HR=2.30，95%CI：1.28-4.15，p=0.005）。基线D-二聚体水平升高是与VTE无关的死亡风险因素（HR=1.07，95%CI：1.05-1.08，p<0.001），并且也预测了发生VTE患者的死亡风险。较高的科纳纳评分既预测了VTE风险也预测了死亡风险，但未预测癌症相关VTE后的死亡情况。总之，多状态建模是分析癌症人群VTE发生时间队列数据的一种非常有效的方法，应用于癌症相关VTE的观察性研究和干预性研究。
