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dc.contributor.authorTimp, Jasmijn F.
dc.contributor.authorBrækkan, Sigrid Kufaas
dc.contributor.authorLijfering, Willem M.
dc.contributor.authorvan Hylckama Vlieg, Astrid
dc.contributor.authorHansen, John-Bjarne
dc.contributor.authorRosendaal, Frits Richard
dc.contributor.authorle Cessie, Saskia
dc.contributor.authorCannegieter, Suzanne C.
dc.date.accessioned2020-03-10T12:41:51Z
dc.date.available2020-03-10T12:41:51Z
dc.date.issued2019-10-11
dc.description.abstract<i>Background</i> - Recurrent venous thromboembolism (VTE) is common. Current guidelines suggest that patients with unprovoked VTE should continue anticoagulants unless they have a high bleeding risk, whereas all others can stop. Prediction models may refine this dichotomous distinction, but existing models apply only to patients with unprovoked first thrombosis. We aimed to develop a prediction model for all patients with first VTE, either provoked or unprovoked.<p><p> <i>Methods and findings</i> - Data were used from two population-based cohorts of patients with first VTE from the Netherlands (Multiple Environment and Genetic Assessment of Risk Factors for Venous Thrombosis [MEGA] follow-up study, performed from 1994 to 2009; model derivation; <i>n</i> = 3,750) and from Norway (Tromsø study, performed from 1999 to 2016; model validation; <i>n</i> = 663). Four versions of a VTE prediction model were developed: model A (clinical, laboratory, and genetic variables), model B (clinical variables and fewer laboratory markers), model C (clinical and genetic factors), and model D (clinical variables only). The outcome measure was recurrent VTE. To determine the discriminatory power, Harrell’s C-statistic was calculated. A prognostic score was assessed for each patient. Kaplan-Meier plots for the observed recurrence risks were created in quintiles of the prognostic scores. For each patient, the 2-year predicted recurrence risk was calculated. Models C and D were validated in the Tromsø study.<p><p> During 19,201 person-years of follow-up (median duration 5.7 years) in the MEGA study, 507 recurrences occurred. Model A had the highest predictive capability, with a C-statistic of 0.73 (95% CI 0.71–0.76). The discriminative performance was somewhat lower in the other models, with C-statistics of 0.72 for model B, 0.70 for model C, and 0.69 for model D. Internal validation showed a minimal degree of optimism bias. Models C and D were externally validated, with C-statistics of 0.64 (95% CI 0.62–0.66) and 0.65 (95% CI 0.63–0.66), respectively. According to model C, in 2,592 patients with provoked first events, 367 (15%) patients had a predicted 2-year risk of >10%, whereas in 1,082 patients whose first event was unprovoked, 484 (45%) had a predicted 2-year risk of <10%. A limitation of both cohorts is that laboratory measurements were missing in a substantial proportion of patients, which therefore were imputed.<p><p> <i>Conclusions</i> - The prediction model we propose applies to patients with provoked or unprovoked first VTE—except for patients with (a history of) cancer—allows refined risk stratification, and is easily usable. For optimal individualized treatment, a management study in which bleeding risks are also taken into account is necessary.en_US
dc.identifier.citationTimp JF, Brækkan SK, Lijfering WM, van Hylckama Vlieg A, Hansen JB, Rosendaal FR, le Cessie S, Cannegieter SC. Prediction of recurrent venous thrombosis in all patients with a first venous thrombotic event: The Leiden Thrombosis Recurrence Risk Prediction model (L-TRRiP). Nature Methods. 2019;16:e1002883(10):1-22en_US
dc.identifier.cristinIDFRIDAID 1743446
dc.identifier.doi10.1371/journal.pmed.1002883
dc.identifier.issn1548-7091
dc.identifier.issn1548-7105
dc.identifier.urihttps://hdl.handle.net/10037/17705
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalNature Methods
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titlePrediction of recurrent venous thrombosis in all patients with a first venous thrombotic event: The Leiden Thrombosis Recurrence Risk Prediction model (L-TRRiP)en_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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