IJGII Inernational Journal of Gastrointestinal Intervention

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Int J Gastrointest Interv 2019; 8(3): 116-122

Published online July 31, 2019 https://doi.org/10.18528/ijgii190010

Copyright © International Journal of Gastrointestinal Intervention.

Management of antithrombotic agents and current issues in patients undergoing endoscopic submucosal dissection

Chan Hyuk Park *

Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea

Correspondence to:*Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, 153 Gyeongchun-ro, Guri 11923, Korea.
E-mail address: yesable7@gmail.com (C.H. Park). ORCID: https://orcid.org/0000-0003-3824-3481

Received: July 1, 2019; Revised: July 19, 2019; Accepted: July 19, 2019

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Postoperative bleeding is a common adverse event in endoscopic submucosal dissection (ESD) and may be life-threatening. Postoperative bleeding occurs frequently in patients treated with antithrombotic agents, including aspirin, antiplatelet agents, warfarin, and non-vitamin K-dependent oral anticoagulants. Due to the aging population and the increase in the risk of thromboembolic disease, the number of patients who require antithrombotic therapy has increased. To date, several clinical studies have been conducted and several global guidelines have been updated. Nevertheless, determining the optimal use of antithrombotic agents in patients undergoing ESD is still challenging, and recommendations for the use of these agents vary slightly across different guidelines. In this review, I summarized the current guidelines and discussed several ongoing issues with the management of antithrombotic agents in patients undergoing ESD.

Keywords: Anticoagulants, Antiplatelet agent, Antithrombotic agent, Aspirin, Endoscopic mucosal resection

Endoscopic submucosal dissection (ESD) is a minimally invasive technique, that is widely used for the management of early gastrointestinal tumors, especially in Asia.13 It has the advantage of providing higher en bloc and complete resection rates compared to endoscopic mucosal resection (EMR).4 However, postoperative bleeding, which can be life-threatening, is a concern following ESD.5,6 The incidence of post-ESD bleeding ranges between 0% to 15.6% for gastric ESD,7,8 1.5% to 6.6% for colorectal ESD,812 and 0% to 5.2% for esophageal ESD.8,13,14

The concern for postoperative bleeding is even greater when patients taking antithrombotic agents require ESD. As the population ages and the risk of thromboembolic disease increases, the number of patients who require antithrombotic therapy also increases.15,16 Moreover, various antithrombotic medications, including aspirin, nonsteroidal anti-inflammatory drugs, adenosine diphosphate receptor/P2Y12 inhibitors, glycoprotein IIb/IIIa inhibitors, prostacyclin, thromboxane inhibitors, phosphodiesterase inhibitors, vitamin K antagonists, heparin, and non-vitamin K-dependent oral anticoagulants (NOAC), are available.17 To cope with these changes, many clinical studies are being conducted and several global guidelines are being updated.1723 Additionally, a web-based application has recently been developed to help manage antithrombotic agents before endoscopy.24 Nevertheless, the use of antithrombotic agents in patients undergoing endoscopy is still complex and recommendations for the use of these agents vary slightly across different guidelines. In this review, I summarize the recommendations from recent guidelines and discuss several issues with the management of antithrombotic agents in patients undergoing ESD.

The major statements on antithrombotic agents that focus on ESD in the recent guidelines are summarized in Table 1.1723 Most guidelines recommend the management of antithrombotic therapy according to the risk of bleeding during endoscopic procedures. However, in the American Society for Gastrointestinal Endoscopy (ASGE) guidelines published in 2009, the risk of bleeding due to ESD had not been rated but polypectomy was considered a high-risk procedure.18 Thus, we applied the following statement to ESD: “When high-risk procedures are planned, clinicians may elect to discontinue aspirin and/or nonsteroidal anti-inflammatory drugs for 5 to 7 days before the procedure, depending on the underlying indication for antiplatelet therapy.” In the ASGE guideline published in 2016, ESD was rated as a higher-risk procedure, similar to EMR and polypectomy.17 In this guideline many new statements were developed regarding the use of antiplatelet agents and anticoagulants. Summaries of the recommendations for the use of antiplatelet agents in high-risk procedures are: (1) low-dose aspirin may be continued during the perioperative period, (2) monotherapy with thienopyridine derivatives can be discontinued or switched to low-dose aspirin monotherapy during the perioperative period, and (3) dual antiplatelet therapy can be replaced with low-dose aspirin monotherapy during the perioperative period. Regarding anticoagulants, the guideline recommends that anticoagulants be discontinued during the perioperative period and replaced with heparin-bridge therapy in patients at a high risk of thromboembolic events. Compared to the previous version of the guideline, the 2016 ASGE guideline emphasized the continuation of low-dose aspirin during ESD.

In the European Society of Gastrointestinal Endoscopy (ESGE) guidelines published in 2011 and 2016, ESD, EMR, and polypectomy were considered high-risk procedures.19,20 In the 2011 ESGE guideline, discontinuation of all antiplatelet agents was recommended for both EMR and ESD if the patient was not at a high risk of thromboembolic events.19 In the 2016 ESGE guidelines, however, continuation of low-dose aspirin is recommended during ESD in patients undergoing dual antiplatelet therapy.20 Low-dose aspirin or P2Y12 receptor antagonist monotherapy can be discontinued during the perioperative period if patients are at a low risk of thromboembolic events. The recent guidelines also support the continuation of low-dose aspirin during ESD in patients at a high risk of thromboembolic events. For anticoagulation therapy, it is recommended that warfarin be discontinued in patients at a low risk of thromboembolic events and be replaced with low molecular weight heparin during the perioperative period in patients at a high risk of thromboembolic events.

The Japan Gastroenterological Endoscopy Society (JGES) guidelines published in 2014 also classified ESD, EMR, and polypectomy as high-risk procedures.21 The JGES guidelines support the continuation of low-dose aspirin during ESD in patients at a high risk of thromboembolic events. The discontinuation of thienopyridine derivatives is recommended during ESD. However, their replacement with aspirin or cilostazol is recommended in patients at a high risk of thromboembolic events. Additionally, it is recommended that warfarin and dabigatran be replaced with heparin during the perioperative period. In 2018, the JGES published further statements concerning anticoagulants including NOAC.22 Recommendations different from those in other guidelines were presented. These recommendations are: “For gastroenterological endoscopic procedures with a high risk of bleeding in patients on warfarin therapy, heparin replacement may increase the risk of postoperative bleeding. As an alternative to heparin replacement, continued warfarin treatment in patients where the international normalized ratio falls within the therapeutic range, or a temporary switch to NOAC in those with non-valvular atrial fibrillation, should be considered during endoscopic procedures.”22 These statements are notable because the existing guidelines recommend either the discontinuation of warfarin or heparin-bridge therapy according to the risk of thromboembolic events. On the contrary, the 2018 JGES guidelines suggest that the continuation of warfarin may be better than heparin-bridge therapy in patients at a high risk of thromboembolic events.

The joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) guidelines were published in 2018.23 The most important difference between these and other guidelines is that ESD was rated as an ultrahigh-risk procedure. A category for ultrahigh-risk procedures was added to the APAGE/APSDE guidelines because: (1) ESD is frequently performed in this area of the world, (2) many relevant studies were conducted in Asia, and (3) the opinions and clinical practice patterns for the management of antithrombotic agents significantly differ between Eastern and Western endoscopists.23,25,26 For high-risk procedures such as polypectomy, it is recommended that low-dose aspirin be continued in patients undergoing low-dose aspirin monotherapy or dual anti-platelet therapy. However, this recommendation does not apply to an ultrahigh-risk procedure such as ESD. In other words, the discontinuation of low-dose aspirin in patients who are scheduled for ESD may be considered. For anticoagulation therapy, heparin-bridge therapy is recommended for patients who are undergoing treatment with warfarin, but not those being treated with NOAC.

The recent guidelines have two concepts in common: (1) the risk of bleeding following ESD is high or ultrahigh and (2) antithrombotic agents should be discontinued based on the risk of thromboembolic events. However, there are issues with differences in the guidelines around the management of antithrombotic agents. These issues are: (1) the continuation of low-dose aspirin in patients at a high risk of thromboembolic events (such as those with dual antiplatelet therapy), (2) differences in the risk of bleeding or thromboembolic events between patients in Eastern and Western countries, and (3) the recommendation of heparin-bridge therapy during ESD in patients at a high risk of thromboembolic events. These issues will be discussed in the subsequent sections.

Although the APAGE/APSDE guidelines do not recommend the continuation of low-dose aspirin therapy during ultrahigh-risk procedures such as ESD, most guidelines suggest that low-dose aspirin therapy can be continued even during ESD. Such a recommendation is based on the results of several studies that showed that low-dose aspirin did not increase the post-ESD bleeding rate.2729 A meta-analysis found that aspirin did not significantly increase post-ESD bleeding (odds ratio [95% confidence interval]: 1.81 [0.85–3.83]).30 Considering that thromboembolic events usually result in more serious sequelae than post-ESD bleeding, the continuation of low-dose aspirin therapy during ESD is reasonable for patients at a high thromboembolic risk.

Given that a meta-analysis showed that low-dose aspirin had a tendency of increasing post-ESD bleeding in patients, the continued use of low-dose aspirin may be of concern in patients at a higher risk of bleeding, such as those undergoing dual antiplatelet therapy. In a study by Cho et al,31 which was included in the abovementioned meta-analysis, the post-ESD bleeding rate was 3.4% in aspirin non-users, 3.6% in aspirin users who discontinued the use of aspirin, and 21.1% in aspirin users who continued using aspirin. The authors concluded that aspirin should be discontinued in patients at a low risk for thromboembolic diseases to minimize bleeding complications.31 However, the findings of the aforementioned study should be interpreted with caution because 36.8% of patients in the group that continued using aspirin compared to only 5.4% of patients in the group that discontinued the use of aspirin underwent dual antiplatelet therapy. Although the administration of antiplatelet agents other than aspirin was discontinued at least seven days before ESD and was resumed seven days after the ESD, the high post-ESD bleeding rate in the group that continued using aspirin might be due to other antiplatelet agents. In a study by Sanomura et al,27 similar numbers of patients who were taking either antiplatelet agents or anticoagulants were included in the low-dose aspirin continuation and discontinuation groups (32% in each group). In the aforementioned study, the post-ESD bleeding rate did not differ between the groups (continuation 3.6% vs discontinuation 4.8%, P > 0.999). When the impact of dual antiplatelet therapy is excluded, the continuation of low-dose aspirin therapy alone may not significantly increase the risk of post-ESD bleeding.

Harada et al,32 in a recent study, evaluated the impact of low-dose aspirin continuation during ESD according to the dual antiplatelet therapy. In their study, the continuation of low-dose aspirin did not increase post-ESD bleeding (continuation 10.7% vs discontinuation 10.3%, P > 0.99) in patients undergoing single low-dose aspirin therapy. In patients who were undergoing dual antiplatelet therapy, the post-ESD bleeding rate tended to be higher in the low-dose aspirin continuation group than in the discontinuation group (23.1% vs 5.0%, P = 0.141). Although the statistical power was low in the study, the study findings implied that concerns about low-dose aspirin continuation remain among patients at a high thromboembolic risk, such as those undergoing dual antiplatelet therapy.

Concerns that the continuation of aspirin may increase the risk of post-ESD bleeding have been noted in the APAGE/APSDE guidelines. The guidelines recommends the interruption of all antithrombotic agents during ultrahigh-risk procedures provided that the perceived benefits of the procedure outweigh the patient’s thromboembolic risk.23 As mentioned earlier, ultrahigh-risk procedures were defined in the APAGE/APSDE guidelines for several reasons, including the difference in clinical practices between Eastern and Western endoscopists during the management of antithrombotic agents. Lee et al25 conducted a study on this issue, which involved 105 Eastern and 106 Western endoscopists. In the study, Eastern endoscopists usually discontinued aspirin more than seven days before polypectomy (76.3%), while 39.6% of Western endoscopists did not stop the use of aspirin before polypectomy. Additionally, Eastern endoscopists resumed aspirin administration one to three days after polypectomy (44.8%), while Western endoscopists resumed aspirin administration on the day of polypectomy (35.9%). Interestingly, more Eastern than Western endoscopists (22.4% vs 8.1%, P = 0.006) agreed that the risk of bleeding is higher in Asians than in other ethnic groups. Additionally, more Eastern endoscopists agreed that the risk of thromboembolism is higher in whites than in other ethnic groups (39.4% vs 21.0%, P = 0.007). Eastern endoscopists seem to believe that following Western guidelines is dangerous because it leads to an increased risk of bleeding in Asian patients.26 Although differences in bleeding or thromboembolic risk among patients of different ethnicities have not been well documented, either the threshold for antiplatelet therapy or the metabolism of warfarin differs between Easterners and Westerners.3336 Taking into consideration the current evidence and perspective, it is necessary to refer to both Eastern and Western guidelines during the management of antithrombotic agents for Asian patients who undergo ESD.

Traditionally, heparin-bridge therapy during the perioperative period was thought to be necessary to minimize thromboembolic risk due to the discontinuation of warfarin during this period. Most of the current guidelines, including the APAGE/APSDE guidelines, recommend heparin-bridge therapy during the period of warfarin discontinuation if patients have a high thromboembolic risk.17,20,23 However, heparin-bridge therapy increases the risk of post-ESD bleeding from 4.2 to 34.4 times.3739 Additionally, there is no consensus on whether heparin-bridge therapy is an effective strategy. Recently, an interesting prospective observational study on this issue was conducted by Harada et al40 They investigated the differences in clinical outcomes, including post-ESD bleeding, operation time, and length of hospital stay, between the continuous use of low-dose warfarin and heparin-bridge therapy in patients. Although the post-ESD bleeding rate did not differ between the groups, it tended to be lower in the continuous use of low-dose warfarin group than in the heparin-bridge therapy group (9.1% vs 21.7%, P = 0.414). The operation time and length of hospital stay were significantly shorter in the continuous use of low-dose warfarin group than in the heparin-bridge therapy group. Although a large-scale study is required to reach a definitive conclusion, the continuous use of warfarin may be another treatment option for patients at a high thromboembolic risk.

The effect of the continuous use of warfarin was also investigated in the field of cardiology. In a randomized-controlled trial performed by Birnie et al,41 the continuous use of warfarin during pacemaker or implantable cardioverter-defibrillator surgery markedly reduced the incidence of clinically significant device-pocket hematoma compared to heparin-bridge therapy (16.0% vs 3.5%, P < 0.001). The number of days of hospitalization due to hematoma in the continuous use of warfarin group was shorter than that in the heparin-bridge therapy group (1.2% vs 4.7%, P = 0.006). The rate of interruption of anticoagulation therapy due to hematoma was also lower in the continuous use of warfarin group than in the heparin-bridge therapy group (14.2% vs 3.2%, P < 0.001). The concept of an “anticoagulant stress test” may provide an explanation for these findings.41,42 If patients undergo surgery while receiving full-dose anticoagulation therapy, every minor bleed will be detected and appropriately treated while the wound is still open.41 On the contrary, in patients undergoing heparin-bridge therapy, some minor bleeds may not be identified during the operation, which will then cause bleeding after surgery when full-dose anticoagulation therapy is restarted. This hypothesis may apply to patients who undergo heparin-bridge therapy during ESD. Although the continuous use of warfarin may increase the incidence of bleeding during ESD, potential bleeds on the iatrogenic ulcer bed can be detected and appropriately coagulated. If ESD was successfully performed despite the continuous use of warfarin, the risk of post-ESD bleeding may decrease compared to if the patient underwent heparin-bridge therapy. In this respect, the recently updated JGES guidelines, which emphasize the continued use of warfarin as an alternative treatment to heparin-bridge therapy, is worth considering.

Although current guidelines cover esophageal, gastric, and colorectal ESD, the most studied type is gastric ESD. Few studies are available on colorectal ESD and there is no study on esophageal ESD and the use of antithrombotic agents.12,20,43 Presently, antithrombotic agents in esophageal or colorectal ESD should be selected based on the results of studies on gastric ESD.

In this review, guideline recommendations for the management of antithrombotic agents in patients who undergo ESD were discussed. Because ESD is a high-risk procedure, thienopyridine derivatives may be discontinued to reduce the risk of post-ESD bleeding. However, in patients undergoing dual antiplatelet therapy, switching to a single low-dose aspirin therapy can be considered when thienopyridine derivatives are discontinued during the perioperative period. Most of the recent guidelines support the continuous use of low-dose aspirin even in patients who undergo ESD. However, there is still a concern about the increased risk of bleeding with the use of low-dose aspirin in patients undergoing dual antiplatelet therapy, especially in the Asian population.

In patients receiving anticoagulants, either warfarin or NOAC can be discontinued depending on the risk of thromboembolic events. For patients at a high risk of thromboembolic events, most current guidelines recommend the discontinuation of warfarin and heparin-bridge therapy. However, the continuous use of warfarin can also be considered in patients who undergo ESD, as recommended in the JGES guidelines.22

  1. Park CH, Lee H, Kim DW, Chung H, Park JC, Shin SK, et al. Clinical safety of endoscopic submucosal dissection compared with surgery in elderly patients with early gastric cancer: a propensity-matched analysis. Gastrointest Endosc. 2014;80:599-609.
    Pubmed CrossRef
  2. Park CH, Shin S, Park JC, Shin SK, Lee SK, Lee YC, et al. Long-term outcome of early gastric cancer after endoscopic submucosal dissection: expanded indication is comparable to absolute indication. Dig Liver Dis. 2013;45:651-6.
    Pubmed CrossRef
  3. Daoud DC, Suter N, Durand M, Bouin M, Faulques B, von Renteln D. Comparing outcomes for endoscopic submucosal dissection between Eastern and Western countries: a systematic review and meta-analysis. World J Gastroenterol. 2018;24:2518-36.
    Pubmed KoreaMed CrossRef
  4. Cao Y, Liao C, Tan A, Gao Y, Mo Z, Gao F. Meta-analysis of endoscopic submucosal dissection versus endoscopic mucosal resection for tumors of the gastrointestinal tract. Endoscopy. 2009;41:751-7.
    Pubmed CrossRef
  5. Park CH, Lee SK. Preventing and controlling bleeding in gastric endoscopic submucosal dissection. Clin Endosc. 2013;46:456-62.
    Pubmed KoreaMed CrossRef
  6. Kim EH, Park SW, Nam E, Eun CS, Han DS, Park CH. Role of second-look endoscopy and prophylactic hemostasis after gastric endoscopic submucosal dissection: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2017;32:756-68.
    Pubmed CrossRef
  7. Oda I, Suzuki H, Nonaka S, Yoshinaga S. Complications of gastric endoscopic submucosal dissection. Dig Endosc. 2013;25 Suppl 1:71-8.
    Pubmed CrossRef
  8. Toyonaga T, Man-i M, East JE, Nishino E, Ono W, Hirooka T, et al. 1,635 Endoscopic submucosal dissection cases in the esophagus, stomach, and colorectum: complication rates and long-term outcomes. Surg Endosc. 2013;27:1000-8.
    Pubmed KoreaMed CrossRef
  9. Saito Y, Uraoka T, Matsuda T, Emura F, Ikehara H, Mashimo Y, et al. Endoscopic treatment of large superficial colorectal tumors: a case series of 200 endoscopic submucosal dissections (with video). Gastrointest Endosc. 2007;66:966-73.
    Pubmed CrossRef
  10. Fujishiro M, Yahagi N, Kakushima N, Kodashima S, Muraki Y, Ono S, et al. Outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms in 200 consecutive cases. Clin Gastroenterol Hepatol. 2007;5:678-83 quiz 645..
    Pubmed CrossRef
  11. Saito Y, Uraoka T, Yamaguchi Y, Hotta K, Sakamoto N, Ikematsu H, et al. A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video). Gastrointest Endosc. 2010;72:1217-25.
    Pubmed CrossRef
  12. Terasaki M, Tanaka S, Shigita K, Asayama N, Nishiyama S, Hayashi N, et al. Risk factors for delayed bleeding after endoscopic submucosal dissection for colorectal neoplasms. Int J Colorectal Dis. 2014;29:877-82.
    Pubmed CrossRef
  13. Isomoto H, Yamaguchi N, Minami H, Nakao K. Management of complications associated with endoscopic submucosal dissection/ endoscopic mucosal resection for esophageal cancer. Dig Endosc. 2013;25 Suppl 1:29-38.
    Pubmed CrossRef
  14. Kagemoto K, Oka S, Tanaka S, Miwata T, Urabe Y, Sanomura Y, et al. Clinical outcomes of endoscopic submucosal dissection for superficial Barrett’s adenocarcinoma. Gastrointest Endosc. 2014;80:239-45.
    Pubmed CrossRef
  15. Béjot Y, Bailly H, Graber M, Garnier L, Laville A, Dubourget L, et al. Impact of the ageing population on the burden of stroke: the Dijon Stroke Registry. Neuroepidemiology. 2019;52:78-85.
    Pubmed CrossRef
  16. Chugh SS, Roth GA, Gillum RF, Mensah GA. Global burden of atrial fibrillation in developed and developing nations. Glob Heart. 2014;9:113-9.
    Pubmed CrossRef
  17. Acosta RD, Abraham NS, Chandrasekhara V, Chathadi KV, Early DS, et al; ASGE Standards of Practice Committee. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016;83:3-16.
    Pubmed CrossRef
  18. Anderson MA, Ben-Menachem T, Gan SI, Appalaneni V, Banerjee S, et al; ASGE Standards of Practice Committee. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc. 2009;70:1060-70.
    Pubmed CrossRef
  19. Boustière C, Veitch A, Vanbiervliet G, Bulois P, Deprez P, Laquiere A, et al. Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2011;43:445-61.
    Pubmed CrossRef
  20. Veitch AM, Vanbiervliet G, Gershlick AH, Boustiere C, Baglin TP, Smith LA, et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Gut. 2016;65:374-89.
    Pubmed KoreaMed CrossRef
  21. Fujimoto K, Fujishiro M, Kato M, Higuchi K, Iwakiri R, Sakamoto C, et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc. 2014;26:1-14.
    Pubmed CrossRef
  22. Kato M, Uedo N, Hokimoto S, Ieko M, Higuchi K, Murakami K, et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment: 2017 appendix on anticoagulants including direct oral anticoagulants. Dig Endosc. 2018;30:433-40.
    Pubmed CrossRef
  23. Chan FKL, Goh KL, Reddy N, Fujimoto K, Ho KY, Hokimoto S, et al. Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines. Gut. 2018;67:405-17.
    Pubmed KoreaMed CrossRef
  24. Nutalapati V, Tokala KT, Desai M, Kanakadandi V, Olyaee M, Parasa S, et al. Development and validation of a web-based electronic application in managing antithrombotic agents in patients undergoing GI endoscopy. Gastrointest Endosc. 2019 [Epub ahead of print].
    Pubmed CrossRef
  25. Lee SY, Tang SJ, Rockey DC, Weinstein D, Lara L, Sreenarasimhaiah J, et al. Managing anticoagulation and antiplatelet medications in GI endoscopy: a survey comparing the East and the West. Gastrointest Endosc. 2008;67:1076-81.
    Pubmed CrossRef
  26. Lee SY. The type of the patient should be considered on discontinuation of anticoagulant and antiplatelet therapy. Gut. 2009;58:153-4 author reply 154..
    Pubmed
  27. Sanomura Y, Oka S, Tanaka S, Numata N, Higashiyama M, Kanao H, et al. Continued use of low-dose aspirin does not increase the risk of bleeding during or after endoscopic submucosal dissection for early gastric cancer. Gastric Cancer. 2014;17:489-96.
    Pubmed KoreaMed CrossRef
  28. Tounou S, Morita Y, Hosono T. Continuous aspirin use does not increase post-endoscopic dissection bleeding risk for gastric neoplasms in patients on antiplatelet therapy. Endosc Int Open. 2015;3:E31-8.
    Pubmed KoreaMed
  29. Igarashi K, Takizawa K, Kakushima N, Tanaka M, Kawata N, Yoshida M, et al. Should antithrombotic therapy be stopped in patients undergoing gastric endoscopic submucosal dissection?. Surg Endosc. 2017;31:1746-53.
    Pubmed CrossRef
  30. Jaruvongvanich V, Sempokuya T, Wijarnpreecha K, Ungprasert P. Continued versus interrupted aspirin use and bleeding risk after endoscopic submucosal dissection of gastric neoplasms: a meta-analysis. Ann Gastroenterol. 2018;31:344-9.
    Pubmed KoreaMed
  31. Cho SJ, Choi IJ, Kim CG, Lee JY, Nam BH, Kwak MH, et al. Aspirin use and bleeding risk after endoscopic submucosal dissection in patients with gastric neoplasms. Endoscopy. 2012;44:114-21.
    Pubmed CrossRef
  32. Harada H, Suehiro S, Murakami D, Nakahara R, Nagasaka T, Ujihara T, et al. Feasibility of gastric endoscopic submucosal dissection with continuous low-dose aspirin for patients receiving dual antiplatelet therapy. World J Gastroenterol. 2019;25:457-68.
    Pubmed KoreaMed CrossRef
  33. Morimoto T, Fukui T, Lee TH, Matsui K. Application of U.S. guidelines in other countries: aspirin for the primary prevention of cardiovascular events in Japan. Am J Med. 2004;117:459-68.
    Pubmed CrossRef
  34. Takahashi H, Wilkinson GR, Caraco Y, Muszkat M, Kim RB, Kashima T, et al. Population differences in S-warfarin metabolism between CYP2C9 genotype-matched Caucasian and Japanese patients. Clin Pharmacol Ther. 2003;73:253-63.
    Pubmed CrossRef
  35. Takahashi H, Wilkinson GR, Nutescu EA, Morita T, Ritchie MD, Scordo MG, et al. Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African-Americans. Pharmacogenet Genomics. 2006;16:101-10.
    Pubmed CrossRef
  36. Takahashi H, Ieiri I, Wilkinson GR, Mayo G, Kashima T, Kimura S, et al. 5′-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients. Blood. 2004;103:3055-7.
    Pubmed CrossRef
  37. Sato C, Hirasawa K, Koh R, Ikeda R, Fukuchi T, Kobayashi R, et al. Postoperative bleeding in patients on antithrombotic therapy after gastric endoscopic submucosal dissection. World J Gastroenterol. 2017;23:5557-66.
    Pubmed KoreaMed CrossRef
  38. Furuhata T, Kaise M, Hoteya S, Iizuka T, Yamada A, Nomura K, et al. Postoperative bleeding after gastric endoscopic submucosal dissection in patients receiving antithrombotic therapy. Gastric Cancer. 2017;20:207-14.
    Pubmed CrossRef
  39. Gotoda T, Hori K, Iwamuro M, Kono Y, Miura K, Kanzaki H, et al. Evaluation of the bleeding risk with various antithrombotic therapies after gastric endoscopic submucosal dissection. Endosc Int Open. 2017;5:E653-62.
    Pubmed KoreaMed CrossRef
  40. Harada H, Suehiro S, Murakami D, Shimizu T, Nakahara R, Katsuyama Y, et al. Continuous use of low-dose warfarin for gastric endoscopic submucosal dissection: a prospective study. Endosc Int Open. 2017;5:E348-53.
    Pubmed KoreaMed CrossRef
  41. Birnie DH, Healey JS, Wells GA, Verma A, Tang AS, Krahn AD, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med. 2013;368:2084-93.
    Pubmed CrossRef
  42. Robinson M, Healey JS, Eikelboom J, Schulman S, Morillo CA, Nair GM, et al. Postoperative low-molecular-weight heparin bridging is associated with an increase in wound hematoma following surgery for pacemakers and implantable defibrillators. Pacing Clin Electrophysiol. 2009;32:378-82.
    Pubmed CrossRef
  43. Suzuki S, Chino A, Kishihara T, Uragami N, Tamegai Y, Suganuma T, et al. Risk factors for bleeding after endoscopic submucosal dissection of colorectal neoplasms. World J Gastroenterol. 2014;20:1839-45.
    Pubmed KoreaMed CrossRef