Xu Yan, Gomes Tara, Wells Philip S, Pequeno Priscila, Johnson Ana, Sholzberg Michelle
Department of Medicine, University of Ottawa, Ottawa, Canada.
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada; Institute for Clinical Evaluative Sciences, Toronto, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.
Thromb Res. 2022 May;213:57-64. doi: 10.1016/j.thromres.2022.02.018. Epub 2022 Feb 24.
Major bleeding is the most serious complication of oral anticoagulants (OACs). While consensus criteria to define major bleeding have been established by the International Society for Thrombosis and Haemostasis (ISTH), Bleeding Academic Research Consortium (BARC) and Thrombolysis in Myocardial Infarction (TIMI), significant variability exists across these definitions. We sought to evaluate the agreement of cases identified by the three definitions and to assess their effect on mortality and OAC resumption.
We used a dataset of individuals ≥66 years in Ontario, Canada presenting with OAC-related bleeding from 2010 to 2015. For case agreement, we calculated Cohen's κ between the three major bleeding definitions. We used multivariate regression to determine differences in mortality and OAC resumption among ISTH, BARC and TIMI-defined major bleeds.
Among 2002 cases of OAC-related bleeding, agreement in case identification between ISTH and BARC was substantial (Cohen's κ = 0.69); however, agreement between TIMI and other definitions were poor. Using 30-day mortality of clinically relevant non-major bleeds as comparator, ISTH-, BARC- and TIMI-defined major bleeds conferred 3.3-, 3.2- and 5.9-fold increased risk. Among survivors, 50% with ISTH- and BARC-defined major bleeds resumed OACs at 180 days, compared to 31% of TIMI-associated cases.
Major bleeds identified by ISTH and BARC criteria showed good agreement and similar prognostic utility, whereas TIMI criteria identified patients at greater clinical risk. Our results highlight the need to revise major bleeding definitions based on criteria that are independently predictive of clinically relevant morbidity and mortality to more effectively reflect the risk associated with major bleeding and appropriately influence anticoagulant therapy decisions.
大出血是口服抗凝剂（OACs）最严重的并发症。虽然国际血栓与止血学会（ISTH）、出血学术研究联盟（BARC）和心肌梗死溶栓（TIMI）已制定了定义大出血的共识标准，但这些定义之间存在显著差异。我们旨在评估这三种定义所识别病例的一致性，并评估它们对死亡率和OAC恢复使用的影响。
我们使用了加拿大安大略省2010年至2015年≥66岁出现OAC相关出血的个体数据集。对于病例一致性，我们计算了三种大出血定义之间的Cohen's κ值。我们使用多变量回归来确定ISTH、BARC和TIMI定义的大出血在死亡率和OAC恢复使用方面的差异。
在2002例OAC相关出血病例中，ISTH和BARC在病例识别上的一致性较高（Cohen's κ = 0.69）；然而，TIMI与其他定义之间的一致性较差。以临床相关非大出血的30天死亡率作为对照，ISTH、BARC和TIMI定义的大出血使风险分别增加了3.3倍、3.2倍和5.9倍。在幸存者中，ISTH和BARC定义的大出血患者中有50%在180天时恢复使用OAC，而TIMI相关病例为31%。
ISTH和BARC标准所识别的大出血显示出良好的一致性和相似的预后效用，而TIMI标准所识别的患者临床风险更高。我们的结果强调需要根据能够独立预测临床相关发病率和死亡率的标准来修订大出血定义，以更有效地反映大出血相关风险并适当影响抗凝治疗决策。
