Peloquin Joanna M, Seraj Siamak M, King Lindsay Y, Campbell Emily J, Ananthakrishnan Ashwin N, Richter James M
Department of Medicine, Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA.
Am J Med. 2016 Jun;129(6):628-34. doi: 10.1016/j.amjmed.2015.11.030. Epub 2015 Dec 20.
Gastrointestinal bleeding is a well-known risk of systemic anticoagulation. However, bleeding in the setting of supratherapeutic anticoagulation may have a milder natural history than unprovoked bleeding. It is a common clinical gestalt that endoscopy is common, but bleeding source identification or intervention is uncommon, yet few data exist to inform this clinical impression. Consequently, we sought to examine our institutional experience with gastrointestinal bleeding in the setting of supratherapeutic international normalized ratio (INR) with the aim of identifying predictors of endoscopically identifiable lesions, interventions, and outcomes.
A retrospective review was conducted at a tertiary referral academic medical center to identify patients presenting with gastrointestinal bleeding in the setting of warfarin and a supratherapeutic INR (>3.5) who underwent an endoscopic procedure. Relevant clinical covariates, endoscopic findings, need for intervention, and outcomes were collected by review of the medical record. Logistic regression adjusting for potential confounders identified predictors of endoscopically significant lesions as well as intervention and outcomes.
A total of 134 patients with INR 3.5 or greater (mean 5.5, range 3.5-17.1) presented with symptoms of gastrointestinal bleeding, most commonly as melena or symptomatic anemia. Antiplatelet agents were used by 54% of patients, and 60% of patients were on concomitant acid suppression on admission. Procedures included esophagogastroduodenoscopy (upper endoscopy; EGD) (n = 128), colonoscopy (n = 73), and video capsule endoscopy (n = 32). Active bleeding at first EGD or colonoscopy was found in only 19 patients (18%), with endoscopic intervention in only 26 patients (25%). At a critical threshold of INR 7.5 at presentation, the likelihood of finding an endoscopically significant lesion fell to <20%. On multivariate logistic regression, concomitant antiplatelet therapy (odds ratio [OR] 2.59; 95% confidence interval [CI], 1.13-5.94), timing of EGD within 12 hours of presentation (OR 3.71; 95% CI, 1.05-13.08), and INR level (OR 0.79; 95% CI, 0.64-0.98) were the only significant independent predictors of identifying a source of bleeding. A risk score incorporating these covariates performed modestly in identifying risk of significant finding on EGD (area under the curve 0.68). We found no association between identification of a significant lesion at EGD and future readmission for gastrointestinal bleeding.
This study demonstrates that the relationship between INR elevation and identification of a bleeding source or endoscopic intervention at EGD are indeed antiparallel. Concomitant antiplatelet therapy increases the likelihood of bleeding source identification and intervention, as does EGD within 12 hours of presentation. However, regardless of source identification or endoscopic intervention, important clinical outcomes were unchanged, suggesting that decisions about endoscopy should be made on a case-by-case basis, particularly in patients with INR > 7.5. Future prospective studies on appropriate indications and timing of endoscopy in such patients are warranted.
胃肠道出血是全身性抗凝治疗的一种已知风险。然而,超治疗剂量抗凝情况下的出血其自然病程可能比不明原因出血更为缓和。在内镜检查很常见,但出血源识别或干预并不常见的临床常见情况中,却鲜有数据来支持这一临床印象。因此,我们试图研究我院在国际标准化比值(INR)超治疗剂量情况下胃肠道出血的经验,目的是确定内镜可识别病变、干预措施及结局的预测因素。
在一家三级转诊学术医疗中心进行回顾性研究,以识别在服用华法林且INR超治疗剂量(>3.5)情况下出现胃肠道出血并接受内镜检查的患者。通过查阅病历收集相关临床协变量、内镜检查结果、干预需求及结局。针对潜在混杂因素进行逻辑回归分析,以确定内镜下显著病变以及干预和结局的预测因素。
共有134例INR为3.5或更高(平均5.5,范围3.5 - 17.1)的患者出现胃肠道出血症状,最常见的是黑便或症状性贫血。54%的患者使用了抗血小板药物,60%的患者入院时同时接受抑酸治疗。检查程序包括食管胃十二指肠镜检查(上消化道内镜检查;EGD)(n = 128)、结肠镜检查(n = 73)和视频胶囊内镜检查(n = 32)。首次EGD或结肠镜检查时发现活动性出血的仅19例患者(18%),仅26例患者(25%)接受了内镜干预。就诊时INR达到7.5这一临界值时,发现内镜下显著病变的可能性降至<20%。多因素逻辑回归分析显示,同时使用抗血小板治疗(比值比[OR] 2.59;95%置信区间[CI],1.13 - 5.94)、在就诊12小时内进行EGD(OR 3.71;95% CI,1.05 - 13.08)以及INR水平(OR 0.79;95% CI,0.64 - 0.98)是识别出血源的仅有的显著独立预测因素。纳入这些协变量的风险评分在识别EGD上显著发现的风险方面表现一般(曲线下面积为0.68)。我们发现EGD时发现显著病变与未来因胃肠道出血再次入院之间无关联。
本研究表明,INR升高与EGD时出血源识别或内镜干预之间的关系确实呈反相关。同时使用抗血小板治疗以及在就诊12小时内进行EGD会增加出血源识别和干预的可能性。然而,无论是否识别出血源或进行内镜干预,重要的临床结局并无变化,这表明关于内镜检查的决策应逐案做出,尤其是在INR > 7.5的患者中。有必要对这类患者内镜检查的适当指征和时机进行未来的前瞻性研究。