Several single-center studies have analyzed the risk factors for EST bleeding [3, 15, 17–19]. Although most of these reports only included patients treated with warfarin, a few recent reports analyzed the risk factors for EST bleeding in patients treated with DOAC [9, 10]. However, these reports compared the risk of EST bleeding between DOAC and warfarin users, and patients not receiving an anticoagulant agent were not considered. As the population ages and the incidence of chronic disease rises, the need for anticoagulants also increases. Particularly, the use of DOAC has increased recently. Thus, the risk factors for bleeding after EST in patients on DOAC were analyzed and compared with those of patients without antithrombotic therapy.
Previous studies showed that the rate of bleeding associated with EST is 1–5% [1–7]. In this study, the rate of EST bleeding was 4.0% (21/524), and the bleeding rate in the DOAC group (14.3%, 6/42) was significantly higher than that in the no-drug group (3.1%, 15/482). While the bleeding rate in the DOAC group in this study was higher than that in previous studies, the bleeding rate in all cases was comparable to those of other reports [9, 10]. In addition, multivariate analysis revealed that the significant risk factors for EST bleeding are DOAC, low platelet count (< 100,000/µl), and old age (> 80 years old). Thus, the rate of EST bleeding in the DOAC group in our study was reliable. Moreover, among the studies that investigated the risk factors for EST bleeding [2, 20, 21], no report revealed the relationship between platelet count and EST bleeding. In our study, as all cases with a platelet count < 100,000 were not associated with liver cirrhosis or idiopathic thrombocytopenia, we suspected that the low platelet count was possibly due to an infection. Some reports described that heparin replacement is a risk factor for post-EST bleeding [9, 10, 15]. However, in our study, there was no EST bleeding in the case with heparin replacement. Therefore, we think that heparin was not related to EST bleeding in our study.
A previous study demonstrated that the rate of severe bleeding associated with EST among anticoagulant users is significantly higher than that among non-users [8]. In our study, although the EST bleeding rate was higher in the DOAC group than in the no-drug group, no significant differences in the extent of bleeding based on the rate of shock, necessity of transfusion, and change in hemoglobin level were found between the groups. In a recent study, the risk of EST bleeding was lower in DOAC users than in warfarin users [9, 10].
Our examination on the DOAC cessation period showed no significant difference in the rate of EST bleeding between DOAC cessation for < 2 days and that for ≥ 2 days. Nonetheless, to decrease the risk of EST bleeding in the DOAC group, a longer cessation of DOAC treatment may be necessary, which may, however, also increase the risk of thromboembolic events [22].
The incidence rate of thromboembolic events after temporary warfarin cessation was 0.7% in a large prospective cohort study that enrolled 6761 patients with 1293 episodes of anticoagulation interruption [23]. In another study, the incidence rate of thromboembolic events after temporary warfarin cessation was 4.2% (4/96) [22]. Moreover, long cessation of anticoagulant therapy of > 48 h was associated with thromboembolic events. Therefore, in patients at risk of thromboembolic events, early resumption of anticoagulant therapy after EST, i.e., within 48 h, may be recommended [22]. Our study followed the JGES guideline, and no thrombotic events were observed during hospitalization.
Various endoscopic approaches for the treatment of EST bleeding have been reported, including injection therapy with HSE [24], balloon compression [25], argon plasma coagulation [26], and hemoclip [27]. Although post-EST bleeding is not associated with increased mortality, morbidity rate and hospital stay duration as well as costs may increase [2]. In our study, all patients with EST bleeding were completely treated with endoscopic hemostasis or conservative therapy. No significant differences in hospital stay between the DOAC and no-drug groups were found. Hence, the JGES guideline was acceptable.
This study has several limitations. The study population was small. In addition, this was a single tertiary referral center retrospective study; thus, some uncontrolled confounding factors that affected the results possibly exist. Given these limitations, a prospective randomized multicenter study is warranted to standardize the approach for DOAC cessation.