Department of Obstetrics, Gynecology and Reproductive Sciences, Yale New Haven Hospital, New Haven, CT.
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO.
Am J Obstet Gynecol. 2023 Sep;229(3):318.e1-318.e14. doi: 10.1016/j.ajog.2023.05.006. Epub 2023 May 16.
Although abnormal uterine bleeding is a known adverse effect of anticoagulant drugs, true rates have not been widely studied. Society-backed recommendations and guidelines do not yet exist for prevention and management of abnormal uterine bleeding among anticoagulated patients.
This study aimed to describe the incidence of new-onset abnormal uterine bleeding among patients receiving therapeutic anticoagulation by anticoagulant class, and to evaluate gynecologic treatment patterns.
We conducted an institutional review board-waived retrospective chart review of female patients aged 18 to 55 years and prescribed therapeutic anticoagulants, including vitamin-K antagonists, low-molecular-weight heparins, and direct oral anticoagulants, in an urban hospital network from January 2015 through January 2020. We excluded patients with antecedent abnormal uterine bleeding and menopause. Associations between abnormal uterine bleeding, anticoagulant class, and other covariates were evaluated with Pearson chi-square and analysis-of-variance tests. The primary outcome, abnormal uterine bleeding odds by anticoagulant class, was modeled with logistic regression. Age, antiplatelet therapy, body mass index, and race were included in our multivariable model. Secondary outcomes included emergency department visits and treatment patterns.
Of the 2479 patients who met the inclusion criteria, 645 were diagnosed with abnormal uterine bleeding after initiating therapeutic anticoagulation. After adjusting for age, race, body mass index, and concurrent use of antiplatelet therapy, those receiving all 3 classes of anticoagulants had higher odds of experiencing abnormal uterine bleeding (adjusted odds ratio, 2.63; confidence interval, 1.70-4.08; P<.001), whereas those taking only direct oral anticoagulants had the lowest odds (adjusted odds ratio, 0.70; confidence interval, 0.51-0.97; P=.032), with vitamin-K antagonists as the reference group. Race other than White was associated with higher odds of abnormal uterine bleeding, as was lower age. The most common hormone therapies used among patients with abnormal uterine bleeding were levonorgestrel intrauterine devices (7.6%; 49/645) and oral progestins (7.6%; 49/645). Sixty-eight patients (10.5%; 68/645) had an emergency department visit for abnormal uterine bleeding; 29.5% (190/645) of patients received a blood transfusion; 12.2% (79/645) began any pharmacologic therapy for bleeding; and 18.8% (121/645) underwent any gynecologic procedure.
Abnormal uterine bleeding occurs frequently among patients on therapeutic anticoagulation. Incidence in this sample varied considerably by anticoagulant class and race; use of single-agent direct oral anticoagulation carried the lowest risk. Important sequelae such as bleeding-related emergency department visits, blood transfusions, and gynecologic procedures were common. Balancing bleeding and clotting risk in patients on therapeutic anticoagulation requires a nuanced approach and should involve collaborative management between hematologists and gynecologists.
尽管抗凝药物会导致异常子宫出血是一种已知的不良反应，但确切的发生率尚未得到广泛研究。目前尚不存在针对抗凝患者异常子宫出血的预防和管理的社会支持推荐和指南。
本研究旨在描述不同抗凝药物类别患者发生新发异常子宫出血的发生率，并评估妇科治疗模式。
我们对 2015 年 1 月至 2020 年 1 月期间在城市医院网络中接受治疗性抗凝治疗的 18 至 55 岁女性患者进行了机构审查委员会豁免的回顾性图表审查，包括维生素 K 拮抗剂、低分子量肝素和直接口服抗凝剂。我们排除了有异常子宫出血和绝经史的患者。采用 Pearson 卡方检验和方差分析评估异常子宫出血、抗凝药物类别和其他协变量之间的关系。使用逻辑回归模型分析抗凝药物类别的异常子宫出血比值比。年龄、抗血小板治疗、体重指数和种族被纳入我们的多变量模型。次要结局包括急诊就诊和治疗模式。
在符合纳入标准的 2479 名患者中，有 645 名在开始接受治疗性抗凝治疗后被诊断为异常子宫出血。在校正年龄、种族、体重指数和同时使用抗血小板治疗后，使用所有 3 种抗凝药物类别的患者发生异常子宫出血的几率更高（校正比值比，2.63；95%置信区间，1.70-4.08；P<.001），而仅使用直接口服抗凝剂的患者发生异常子宫出血的几率最低（校正比值比，0.70；95%置信区间，0.51-0.97；P=.032），以维生素 K 拮抗剂为参照组。非白种人种族与异常子宫出血的几率较高有关，年龄较低也是如此。异常子宫出血患者最常用的激素治疗方法是左炔诺孕酮宫内节育器（7.6%；49/645）和口服孕激素（7.6%；49/645）。68 名患者（10.5%；68/645）因异常子宫出血到急诊就诊；29.5%（190/645）的患者接受了输血；12.2%（79/645）开始使用任何药物治疗出血；18.8%（121/645）接受了任何妇科手术。
异常子宫出血在接受治疗性抗凝治疗的患者中很常见。在本样本中，发生率因抗凝药物类别和种族而异；使用单一药物直接口服抗凝剂的风险最低。常见的重要后果，如出血相关的急诊就诊、输血和妇科手术，也很常见。在接受治疗性抗凝的患者中平衡出血和凝血风险需要一种细致入微的方法，并且应该涉及血液科医生和妇科医生之间的协作管理。
