title: Hypercoagulabilty, venous thromboembolism, and death in patients with cancer. A Multi-State Model.
abstract: 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.
authors.forename: Florian
authors.initials: F
authors.lastname: Posch
authors.forename: Julia
authors.initials: J
authors.lastname: Riedl
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Reitter
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.forename: Christoph
authors.initials: C
authors.lastname: Zielinski
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: 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: cihan.ay@meduniwien.ac.at.
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D016019:Survival Analysis; D019851:Thrombophilia / Q000453:epidemiology* / Q000401:mortality; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000453:epidemiology* / Q000401:mortality; D055815:Young Adult
keywords: Venous thrombosis; cancer; epidemiological studies