Division of Hematology, Oncology, and Blood and Marrow Transplant, Nationwide Children's Hospital/Ohio State University, Columbus, OH; and.
Hemophilia Center, Oregon Health & Science University, Portland, OR.
Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):538-541. doi: 10.1182/hematology.2020000166.
Up to two-thirds of menstruating women experience abnormal uterine bleeding (AUB) when treated with oral anticoagulants. However, the true prevalence of AUB for specific agents remains uncertain, as many of these episodes, while interfering significantly with quality of life and overall health, are not captured by definitions of major bleeding (MB) or clinically relevant nonmajor bleeding (CRNMB) used in clinical trials. A 2017 systematic review determined that women taking rivaroxaban, but not edoxaban or apixaban, had a twofold higher risk of AUB than women taking warfarin. Since then, new data have become available from extension trials, cancer-associated venous thromboembolism trials, pediatric trials, and a few observational studies specifically examining AUB as an outcome. Reported rates of uterine CRNMB were low (around 1%) and similar for rivaroxaban and apixaban in all these studies, and no episodes of uterine bleeding meeting MB criteria were reported. Rates of AUB not meeting MB or CRNMB criteria were much higher, affecting up to 50% of women on rivaroxaban. Only 1 such study included women on apixaban, and no AUB was reported. In pediatric trials, 19% of girls experienced menorrhagia when treated with rivaroxaban. In conclusion, rates of uterine MB and CRNMB were low in all studies, but rates of other types of AUB not meeting these criteria ranged from 15.8% to 50%. We conclude that AUB is underreported due to the limitations of MB/CRNMB criteria despite its substantial impact on quality of life. We urge future investigators to include broader definitions of AUB to better capture the impact of this outcome in menstruating women treated with oral anticoagulants.
多达三分之二的正在接受口服抗凝剂治疗的女性会出现异常子宫出血（AUB）。然而，由于许多此类出血事件虽然显著影响生活质量和整体健康，但并未被临床试验中使用的大出血（MB）或临床相关非大出血（CRNMB）定义所捕获，因此特定药物的 AUB 真实患病率仍不确定。2017 年的一项系统评价确定，服用利伐沙班的女性发生 AUB 的风险是服用华法林的女性的两倍，而服用依度沙班或阿哌沙班的女性则没有这种风险。此后，来自扩展试验、癌症相关静脉血栓栓塞试验、儿科试验和一些专门研究 AUB 作为结局的观察性研究的新数据已经可用。报告的子宫 CRNMB 发生率较低（约为 1%），且在所有这些研究中，利伐沙班和阿哌沙班的发生率相似，且均未报告符合 MB 标准的子宫出血事件。不符合 MB 或 CRNMB 标准的 AUB 发生率要高得多，高达 50%的利伐沙班使用者会出现这种情况。只有 1 项此类研究纳入了接受阿哌沙班治疗的女性，且未报告 AUB。在儿科试验中，19%的女孩在服用利伐沙班时出现月经过多。总之，所有研究中子宫 MB 和 CRNMB 的发生率都较低，但不符合这些标准的其他类型 AUB 的发生率为 15.8%至 50%。我们得出的结论是，尽管 AUB 对生活质量有重大影响，但由于 MB/CRNMB 标准的局限性，导致 AUB 的报告率较低。我们敦促未来的研究人员纳入更广泛的 AUB 定义，以更好地捕捉接受口服抗凝剂治疗的女性的这一结局的影响。
