Thromb Haemost 2016; 115(04): 817-826
DOI: 10.1160/TH15-09-0758
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Hypercoagulabilty, venous thromboembolism, and death in patients with cancer

A Multi-State Model
Florian Posch
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
,
Julia Riedl
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
,
Eva-Maria Reitter
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
,
Alexandra Kaider
2   Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Clinical Biometrics, Medical University of Vienna, Vienna, Austria
,
Christoph Zielinski
3   Clinical Division of Oncology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
,
Ingrid Pabinger
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
,
Cihan Ay
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
› Author Affiliations
Financial support: This study was funded by the Austrian National Bank Memorial Fund (project number 14744); Austrian Science Fund (FWF-SFB-54).
Further Information

Publication History

Received: 27 September 2015

Accepted after major revision: 30 January 2015

Publication Date:
28 November 2017 (online)

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Summary

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.

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