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Several bleeding prediction scores have been described: HAS-BLED, ATRIA, HEMORR<jats:sub>2<\/jats:sub>HAGES and ORBIT. Of these, only HAS-BLED considers quality of anticoagulation control amongst vitamin K antagonist (VKA) users. We hypothesised that predictive value of bleeding risk scores other than HAS-BLED could be improved incorporating time in therapeutic range (TTR) in warfarin-treated patients. Of the 127 adjudicated major bleeding events, 21.3% of events occurred in \u2018low-risk\u2019 HAS-BLED category (1.8 per 100 patient-years), compared to higher proportions (\u226550% of events; ~2.5 per 100 patient-years) in \u2018low-risk\u2019 categories for other scores. Only the \u2018low-risk\u2019 HAS-BLED category was associated with the absence of investigator-defined major bleeding events (OR: 1.46;95% CI: 1.00\u20132.15). \u2018High\u2019 or \u2018medium\/high\u2019 risk categories for the HAS-BLED (p\u2009=\u20090.023) or ORBIT (p\u2009=\u20090.022) scores, respectively, conferred significant risk for adjudicated major bleeding events. On Cox regression analysis, adjudicated major bleeding was associated only with HAS-BLED (HR: 1.62;95% CI: 1.06\u20132.48) and ORBIT (HR: 1.83;95% CI: 1.08\u20133.09) \u2018high-risk\u2019 categories. Adding \u2018labile INR\u2019 (TTR\u2009&lt;\u200965%) to ORBIT, ATRIA and HEMORR<jats:sub>2<\/jats:sub>HAGES significantly improved their reclassification and discriminatory performances. <jats:italic>In conclusion,<\/jats:italic> HAS-BLED categorised adjudicated major bleeding events in low-risk and high-risk patients appropriately, whilst ORBIT and ATRIA categorised most major bleeds into their \u2018low-risk\u2019 patient categories. Adding TTR to ORBIT, ATRIA and HEMORR<jats:sub>2<\/jats:sub>HAGES led to improved predictive performance for major bleeding.<\/jats:p>","DOI":"10.1038\/srep24376","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T10:30:07Z","timestamp":1460457007000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Major Bleeding in Patients with Non-Valvular Atrial Fibrillation: Impact of Time in Therapeutic Range on Contemporary Bleeding Risk Scores"],"prefix":"10.1038","volume":"6","author":[{"given":"Marco","family":"Proietti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keitaro","family":"Senoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre A.","family":"Lane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. 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Speaker for Bayer, BMS\/ Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo. DAL reports Investigatorinitiated educational grants from Bayer Healthcare and Boehringer Ingelheim. Speaker\u2019s bureau for Boehringer Ingelheim, Bristol-Myers-Squibb and Bayer for lectures at educational meetings. Dr Lane is also on the Steering Committee of a Phase IV clinical trial sponsored by Bristol-Myers-Squibb. No other disclosures for other authors.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24376"}}