The study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy: Study Protocol for a Multicenter Prospective Cohort Analysis (The GSATT Study)

Takahisa Fujikawa1; Shigetoshi Naito1,2; Keiji Hirata3; Suguru Hasegawa2

1 Department of Surgery, Kokura Memorial Hospital, Kitakyushu, Fukuoka, Japan;
2 Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Fukuoka, Japan;
3 Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Takahisa Fujikawa, MD, PhD, FACS, Department of Surgery, 3-2-1 Asano, Kokurakita-Ku, Kitakyushu, Fukuoka 802-8555, Japan.
Email: fujikawa-t@kokurakinen.or.jp
Telephone: +81-93-511-2000
Fax: +81-93-511-3240

Received: October 12, 2019
Revised: October 17, 2018
Accepted: October 19, 2018
Published online: December 21, 2019


BACKGROUND: Although there are several large-scale single center cohort studies concerning gastroenterological (GE) surgery in patients receiving antithrombotic therapy (ATT), no clear evidence or guidelines based on multicenter prospective studies have not yet been established. The main purpose of this multicenter prospective cohort study is to assess the safety and feasibility of GE surgery in ATT-received patients during the perioperative period.

METHODS/DESIGN: This is a multicenter, prospective cohort study conducted in Japan. Patients receiving antithrombotic therapy {antiplatelet therapy and/or anticoagulation therapy [warfarin or direct oral anticoagulants (DOACs)]}, as well as undergoing elective GE surgery (including open surgery, laparoscopic surgery, and robot-assisted surgery) are included in the current study; those undergoing emergency GE surgery are excluded. The primary endpoints include intraoperative factors including surgical blood loss, postoperative hemorrhagic complications, and thromboembolic complications; secondary endpoints include other postoperative complications, presence of re-operation, and the length of postoperative stay.

DISCUSSION: The present study can contribute to the determination of the safety and feasibility of elective GE surgery to ATT-received patients and is thought to establish optimal perioperative antithrombotic management for such challenging patient population.

Key words: Study protocol; Multicenter prospective cohort study; Gastroenterological surgery; Antithrombotic therapy; GSATT study

© 2019 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Fujikawa T, Naito S, Hirata K, Hasegawa S. The study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy: Study Protocol for a Multicenter Prospective Cohort Analysis (The GSATT Study). Journal of Gastroenterology and Hepatology Research 2019; 8(6): 1-6 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/2702


In recent years, with the arrival of an aging society, surgical cases with heart disease and cerebrovascular disease have become more common, and most of them are undergoing antithrombotic therapy (ATT; antiplatelet therapy and/or anticoagulation therapy) to prevent secondary thromboembolism. When performing surgical procedures on patients receiving ATT, the continuation of ATT can result in severe bleeding complications during the perioperative period; temporary cessation of ATT can cause fatal thromboembolism[1,2] (Figure 1). Therefore, it is important to set up optimal antithrombotic management to prevent both complications. Especially in gastroenterological (GE) surgery, there are many elderly patients who have concurrent atherosclerotic diseases, requiring resection of GE malignancy or surgery for inflammatory diseases. For this reason, GE surgery in ATT-treated patients is considered to be high risk for both bleeding and thromboembolism.

To date, there is detailed guidance regarding gastrointestinal endoscopic procedures in patients receiving ATT[3-5]. On the other hand, although there are several large-scale single center cohort studies concerning GE surgery in ATT-treated patients[6,7], no clear evidence or guidelines based on multicenter prospective studies have not yet been established. The main purpose of this multicenter prospective cohort study is to assess the safety and feasibility of GE surgery in ATT-received patients during the perioperative period.

Figure 1 The antithrombotic management of ATT-treated patients. In ATT-received patients, perioperative continuation of ATT can result in severe bleeding complications; temporary cessation of ATT can cause fatal thromboembolism. A balance between reducing the risks of both thromboembolism and bleeding must be reached for each patient. Abbreviations: ATT; antithrombotic therapy.


The present study is a multicenter prospective cohort study. The participants are recruited from University of Occupational and Environmental Health, Fukuoka University and Kokura Memorial Hospital in Japan. We obtain written informed consent by investigators from all study patients prior to any screening or inclusion procedures. The trial is organized by the Department of Surgery, Kokura Memorial Hospital, Fukuoka, Japan (Figure 2).

Figure 2 The summary of patient enrollment and data collection in the current GSATT study. Abbreviations: GE; gastroenterological, ATT; antithrombotic therapy, RBC; red blood cell.

Study schedule

The present study was registered as UMIN000038280 on October 12, 2019. Registration started on October 2019. Since this study does not constitute a study aimed at verifying hypotheses, we will not design the number of cases based on statistical considerations. In this study, the evaluation items are summarized in an exploratory manner. A total of 1,000 cases will be enrolled during the study enrollment period. It is anticipated that registration will be completed in two years from the preliminary survey. The estimated study completion date is 2021 (final data collection, date for primary outcome measurement). Outcome results will be collected for 90 days after registration.

Inclusion criteria (Table 1)

Participants are included if all following criteria are met: (1) Patients receiving antithrombotic therapy (antiplatelet therapy and/or anticoagulation therapy), (2) Those undergoing elective GE surgery (including open surgery, laparoscopic surgery, and robot-assisted surgery), and (3) Those being able to submit written consent before the study.

Exclusion criteria (Table 1)

Exclusion criteria were as follows: (1) urgent surgery, (2) being difficult to obtain consent for explanations, such as consciousness levels and examples of cognitive decline, and (3) written consent being not obtained. The number of such patients is reported separately.

The type of GE surgery included (Table 2)

The type of surgery included in the current study is as follows: (1) GE surgery for malignant tumor (e.g. resection of esophageal cancer, gastric cancer, colorectal cancer, liver cancer, biliary tract cancer, pancreatic cancer), and (2) GE surgery for benign diseases, including cholecystectomy, choledocholithotomy, appendectomy, and resection of small intestine.

Table 1 Patient selection criteria and objectives in the current GSATT study.
Patient selection criteria
Inclusion criteria: (1) and (2) and (3)Exclusion criteria: (1) or (2) or (3)
(1) Patients receiving antithrombotic therapy: - antiplatelet therapy; - anticoagulation therapy (warfarin, DOACs)(1) Urgent surgery
(2) Those undergoing elective GE surgery: - open surgery; - laparoscopic surgery; - robot-assisted surgery(2) Being difficult to obtain consent for explanations (e.g. consciousness levels and examples of cognitive decline)
(3) Written consent being obtained before the study(3) Written consent being not obtained
Primary endpointsSecondary endpoints
(1) Intraoperative factors including surgical blood loss, duration of operation, intraoperative RBC transfusion(1) The presence or absence of other postoperative complications
(2) postoperative hemorrhagic complications including luminal (e.g. GI) bleeding, abdominal bleeding, abdominal wall hematoma(2) The presence of postoperative re-operation
(3) postoperative thromboembolic complications including cerebral infarction, myocardial infarction, pulmonary embolism, etc.(3) The length of postoperative stay
Abbreviations: DOAC; direct oral anticoagulant, GE; gastroenterological, GI; gastrointestinal.

Table 2 Details of GE surgery type and antithrombotics included in the GSATT study.
Type of GE surgery included
(1) GE surgery for malignant tumor (a) GI tract surgery: esophageal resection, gastric resection, colorectal resection, etc.
(b) HBP surgery: liver resection, biliary tract resection, pancreatic resection.
(c) Other GE surgery
(2) GE surgery for benign diseases (a) Biliary diseases: cholecystectomy, choledocolithotomy, choledochojejunostomy, etc.
(b) GI diseases: appendectomy, resection of of small intestine, gastrojejunostomy, etc.
(c) Other GE surgery
Type of antithrombotics included
(1) Antiplatelet agents (a) Acetylsalicylic acid (aspirin)
(b) Thienopiridines (clopidogrel, ticlopidine, prasugrel, ticagrelor)
(c) Type III PDE (cilostazol)
(d) Others (EPA, dipyridamole, sarpogrerate, beraprost, limaprost, etc)
(2) Anticoagulant agents(a) Vitamin K antagonist (warfarin)
(b) Direct oral anticoagulants (DOACs): - Direct thrombin inhibitor (dabigatran); - Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban)


The treatment policy (selection of surgical procedure, necessity of conversion in the case of laparoscopic and robotic surgery, postoperative treatment policy, etc.) is conducted in the same fashion as the daily surgical treatment.


The Primary endpoint is as follows: (1) intraoperative factors including surgical blood loss, duration of operation and intraoperative red blood cell (RBC) transfusion, (2) postoperative hemorrhagic complications including luminal (e.g. gastrointestinal) bleeding, abdominal bleeding, and abdominal wall hematoma, and (3) postoperative thromboembolic complications (e.g. cerebral infarction, myocardial infarction, mesenteric infarction, pulmonary embolism).

The secondary endpoint is as follows: (1) The presence or absence of other postoperative complications, (2) The presence of postoperative re-operation, and (3) The length of postoperative stay. The definition and classification Postoperative complications are defined and classified by the JCOG postoperative complication criteria (Clavien-Dindo classification)[8].

Observation and examination contents

Before surgery: (1) Patient characteristics: gender, age at surgery, height, weight. (2) Disease characteristics: malignant diseases (esophageal cancer, stomach cancer, colon cancer, liver cancer, biliary tract cancer, pancreatic cancer, etc.) or benign diseases (cholelithiasis, gallbladder polyps, appendicitis, small intestinal tumors, etc.). (3) The type and mode of surgical procedures planned (Table 2): the type includes elective GE surgery for both malignant and benign diseases, and the mode includes laparoscopic, robot-assisted or open-fashioned surgery. (4) Physical findings: ECOG scale of performance status (PS)[9]. (5) Details of concurrent diseases: history of congestive heart failure and left ventricular dysfunction, history of coronary artery disease (percutaneous coronary intervention and coronary artery bypass graft surgery), history of stroke and transient ischemic attack, hypertension, diabetes, maintenance dialysis, or other pre-existing conditions. (6) Details of antithrombotic drugs (Table 2): antiplatelet drugs (aspirin, clopidogrel, ticlopidine, prasugrel, cilostazol, etc.) and/or anticoagulant agents [warfarin, direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, edoxaban)]. (7) Perioperative antithrombotic therapy management: (a) antiplatelet drugs; preoperative discontinuation, preoperative aspirin continuation, heparin replacement, etc, (b) warfarin; preoperative discontinuation, heparin replacement, DOAC replacement, etc, (c) DOAC; preoperative discontinuation, heparin replacement, etc.

After surgery: (1) Date of operation. (2) Surgical procedures performed: laparoscopic, robot-assisted, or open-fashioned. (3) Presence/absence of conversion to open surgery in case of laparoscopic or robotic surgery. (4) Reason for conversion to open surgery in the case of laparoscopic or robotic surgery. (5) Operative time. (6) Presence/absence of drain. (7) Amount of surgical blood loss. (8) Intraoperative RBC transfusion. (9) Presence of intraoperative accidents.

At discharge: (1) Antithrombotic drug resumption time: antiplatelet agents, warfarin, DOACs. (2) Postoperative complications. (3) Existence of re-operation. (4) Content of complications: date of onset, type, grade, outcome. (5) Length of postoperative stay. (6) Presence/absence of death: cause.

Data collection

The researchers at each hospital conduct investigations using case report forms (CRF) and registration forms. The registration slip will be forwarded to the data center at Kokura Memorial Hospital by fax or email before the surgery begins. The CRF will be completed within two weeks after discharge of the registered patient and sent to the data center. Alternatively, it will be collected at a meeting (scheduled to be held every six months) where relevant facilities participating in this study participate. All data are collected by Kokura Memorial Hospital. The data sharing process within the study is supervised by the data center. Clinical data entry, central monitoring, and data management is also performed.

Statistical analysis

All patients enrolled in the present study are subject to the analysis. After enrollment, ineligible patients are excluded from the present study. Risk factors of excessive intraoperative blood loss, postoperative hemorrhagic complication, and thromboembolic complication are evaluated by both univariate or multivariate analyses. For univariate comparisons, Fisher's exact probability test is used to evaluate categorical variables; alternatively, continuous variables are analyzed by 1-way ANOVA and Kruskal-Wallis tests for normally and nonnormally distributed data, respectively. For multivariate analysis, logistic regression analysis is conducted to determine the independent risk factors. All P-values are two sided and P-values less than 0.05 are considered statistically significant.


ATT includes two types of medications, classified as antiplatelets and anticoagulants. Antiplatelets decrease aggregation of platelets and prevent thrombus formation, and are commonly used for primary and secondary prevention of cardiovascular and cerebrovascular diseases. Antiplatelets include aspirin, thienopyridines, type III phosphodiesterase inhibitor, and other antiplatelet agents[6,10,11]. On the other hand, anticoagulants interfere with the native clotting cascade and prevent the blood clotting, and are generally used for atrial fibrillation, deep vein thrombosis, cardiac endoprostheses[3,4,11], and acute coronary syndrome. These include vitamin K antagonists and DOACs (direct thrombin inhibitor and factor Xa inhibitors)[3,4].

Recently updated guidelines concerning antithrombotic management during non-cardiac surgery showed that the prevention of thromboembolic events is more important than bleeding complications, as it might cause death or severe sequelae[3-5,12,13]. Concerning antiplatelet therapy after implantation of coronary stent, recent AHCC/AHA and ESC guideline said that we should continue antiplatelet medications, at least aspirin monotherapy, in the perioperative period for patients with high risk of thromboembolism[14], but most institutions practically choose to discontinue antiplatelets in case of major digestive surgery with bleeding risks. Although some studies such as POISE-2 study have reported that a modest increase in bleeding risk was observed in single antiplatelet-continued patients during non-cardiac surgery[15,16], most of other studies showed that there was no increase in the significant bleeding events[17,18].

Concerning patients receiving anticoagulation therapy, DOACs are increasingly prescribed for the purpose of preventing arterial or venous thromboembolism. In large clinical trials, DOACs have been demonstrated to have lower rates of intracranial hemorrhage compared to warfarin[19-22]. This difference is primarily due to the difference in mechanism of action in the blood clotting cascade. Recently published review article and ongoing prospective study suggests safety and feasibility of perioperative management of DOACs during noncardiac surgery, which is rather simple and requires no heparin bridging in general[23,24]. Still, there is so far scarce evidence concerning the safety of DOAC-treated patients during the more specific types of surgery such as GE surgery.

Concerning warfarin therapy, heparin bridging is the common management for warfarin[25]. Recently, large-scale randomized controlled trial (BRIDGE study) showed that heparin bridging was not recommended in the case of low bleeding risk surgery due to increased bleeding risks[26]. However, this study included relatively small numbers of GE surgery, and it is not concluded that heparin bridging is unnecessary in major GE surgery. Especially in case of high thromboembolic risks, rigorous perioperative antithrombotic management including heparin bridging, or alternatively DOAC bridging, should be considered to avoid critical thromboembolic complications.

The recently-published review article summarized the outcomes of various types of laparoscopic GE surgery in patients receiving ATT for prevention of thromboembolism[11]. The risk of hemorrhagic or thromboembolic complications during or after these procedures in patients with continued antiplatelets or heparin bridging was not significantly higher than in patients with no ATT or interrupted antiplatelets. The review concluded that there are some promising results for both basic and laparoscopic surgery, although there is scarce evidence concerning the safety of advanced laparoscopic surgery such as colorectal resection or liver resection.

Although there are several large-scale single center cohort studies concerning GE surgery in ATT-treated patients[6,7], no clear evidence or guidelines based on multicenter prospective studies have not yet been established. In this meaning, the current study may contribute to investigate the safety and feasibility of GE surgery in ATT-treated patients using the large-scale real world data. The definite protocol or guidelines will be established using the reliable studies with good design like the current study.


1. Fujikawa T, Noda T, Tada S, Tanaka A. Intractable intraoperative bleeding requiring platelet transfusion during emergent cholecystectomy in a patient with dual antiplatelet therapy after drug-eluting coronary stent implantation (with video). BMJ Case Rep. 2013; Mar 26; 201. [PMID: 23536626]; [PMCID: PMC3618701]; [DOI: 10.1136/bcr-2013-008948]

2. Mita K1, Ito H, Murabayashi R, Sueyoshi K, Asakawa H, Nabetani M, Kamasako A, Koizumi K, Hayashi T. Postoperative bleeding complications after gastric cancer surgery in patients receiving anticoagulation and/or antiplatelet agents. Ann Surg Oncol. 2012; 19(12): 3745-3752. [PMID: 22805868]; [DOI: 10.1245/s10434-012-2500-6]

3. Fujimoto K, Fujishiro M, Kato M, Higuchi K, Iwakiri R, Sakamoto C, Uchiyama S, Kashiwagi A, Ogawa H, Murakami K, Mine T, Yoshino J, Kinoshita Y, Ichinose M, Matsui T; Japan Gastroenterological Endoscopy Society. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc. 2014; 26(1): 1-14. [PMID: 24215155]; [DOI: 10.1111/den.12183]

4. ASGE Standards of Practice Committee, Acosta RD, Abraham NS, Chandrasekhara V, Chathadi KV, Early DS, Eloubeidi MA, Evans JA, Faulx AL, Fisher DA, Fonkalsrud L, Hwang JH, Khashab MA, Lightdale JR, Muthusamy VR, Pasha SF, Saltzman JR, Shaukat A, Shergill AK, Wang A, Cash BD, DeWitt JM. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016; 83(1): 3-16. [PMID: 26621548]; [DOI: 10.1016/j.gie.2015.09.035]

5. Polkowski M, Larghi A, Weynand B, Boustière C, Giovannini M, Pujol B, Dumonceau JM; European Society of Gastrointestinal Endoscopy (ESGE). Learning, techniques, and complications of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Guideline. Endoscopy. 44(2): 190-206. [PMID: 22180307]; [DOI: 10.1055/s-0031-1291543]

6. Fujikawa T, Tanaka A, Abe T, Yoshimoto Y, Tada S, Maekawa H, Shimoike N. Does antiplatelet therapy affect outcomes of patients receiving abdominal laparoscopic surgery? Lessons from more than 1,000 laparoscopic operations in a single tertiary referral hospital. J Am Coll Surg. 2013; 217(6): 1044-1053. [PMID: 24051069]; [DOI: 10.1016/j.jamcollsurg.2013.08.005]

7. Fujikawa T, Tanaka A, Abe T, Yoshimoto Y, Tada S, Maekawa H. Effect of antiplatelet therapy on patients undergoing gastroenterological surgery: thromboembolic risks versus bleeding risks during its perioperative withdrawal. World J Surg. 2015; 39(1): 139-149. [PMID: 25201469]; [DOI: 10.1007/s00268-014-2760-3]

8. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004; 240(2): 205-213. [PMID: 15273542]; [PMCID: PMC1360123]; [DOI: 10.1097/01.sla.0000133083.54934.ae]

9. Sorensen JB, Klee M, Palshof T, Hansen HH. Performance status assessment in cancer patients. An inter-observer variability study. Br J Cancer. 1993; 67(4): 773-775. [PMID: 8471434]; [PMCID: PMC1968363]; [DOI: 10.1038/bjc.1993.140]

10. ASGE Standards of Practice Committee, Anderson MA, Ben-Menachem T, Gan SI, Appalaneni V, Banerjee S, Cash BD, Fisher L, Harrison ME, Fanelli RD, Fukami N, Ikenberry SO, Jain R, Khan K, Krinsky ML, Lichtenstein DR, Maple JT, Shen B, Strohmeyer L, Baron T, Dominitz JA. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc. 2009; 70(6): 1060-1070. [PMID: 19889407]; [DOI: 10.1016/j.gie.2009.09.040]

11. Fujikawa T, Ando K. Safety of laparoscopic surgery in digestive diseases with special reference to antithrombotic therapy: A systematic review of the literature. World J Clin Cases. 2018; 6(14): 767-775. [PMID: 30510941]; [PMCID: PMC6264996]; [DOI: 10.12998/wjcc.v6.i14.767]

12. Kushner FG, Hand M, Smith SC Jr, King SB 3rd, Anderson JL, Antman EM, Bailey SR, Bates ER, Blankenship JC, Casey DE Jr, Green LA, Jacobs AK, Hochman JS, Krumholz HM, Morrison DA, Ornato JP, Pearle DL, Peterson ED, Sloan MA, Whitlow PL, Williams DO; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guid. Catheter Cardiovasc Interv. 2009; 74(7): E25-68. [PMID: 19924773]; [DOI: 10.1002/ccd.22351]

13. Spyropoulos AC, Douketis JD, Gerotziafas G, Kaatz S, Ortel TL, Schulman S. Periprocedural antithrombotic and bridging therapy: recommendations for standardized reporting in patients with arterial indications for chronic oral anticoagulant therapy. J Thromb Haemost. 2012; 10(4): 692-694. [PMID: 22934291]

14. Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016 Sep 6; 134(10): e123-55. [PMID: 27026020]; [DOI: 10.1161/CIR.0000000000000404]

15. Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, VanHelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Baigent C, Chow C, Pettit S, Chrolavicius S, Yusuf S; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014; 370(16): 1494-1503. [PMID: 24679062]; [DOI: 10.1056/NEJMoa1401105]

16. Group PEPTC. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet (London, England). 2000; 355(9212): 1295-1302.]; [DOI: 10.1016/S0140-6736(00)02110-3]

17. Wolf AM, Pucci MJ, Gabale SD, McIntyre CA, Irizarry AM, Kennedy EP, Rosato EL, Lavu H, Winter JM, Yeo CJ. Safety of perioperative aspirin therapy in pancreatic operations. Surg (United States). 2014; 155(1): 39-46. [PMID: 23890963]; [DOI: 10.1016/j.surg.2013.05.031]

18. Fang X, Baillargeon JG, Jupiter DC. Continued Antiplatelet Therapy and Risk of Bleeding in Gastrointestinal Procedures: A Systematic Review. J Am Coll Surg. 2016; 222(5): 890-905e11. [PMID: 27016908]; [DOI: 10.1016/j.jamcollsurg.2016.01.053]

19. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009; 361(12): 1139-1151. [PMID: 19717844]; [DOI: 10.1056/NEJMoa0905561]

20. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011; 365(10): 883-891. [PMID: 21830957]; [DOI: 10.1056/NEJMoa1009638]

21. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators.Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011; 365(11): 981-992. [PMID: 21870978]; [DOI: 10.1056/NEJMoa1107039]

22. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013; 369(22): 2093-2104. [PMID: 24251359]; [DOI: 10.1056/NEJMoa1310907]

23. Verma A, Ha ACT, Rutka JT, Verma S. What Surgeons Should Know About Non-Vitamin K Oral Anticoagulants. JAMA Surg. April 2018. [PMID: 29710221]; [DOI: 10.1001/jamasurg.2018.0374]

24. Douketis JD, Spyropoulos AC, Anderson JM, Arnold DM, Bates SM, Blostein M, Carrier M, Caprini JA, Clark NP, Coppens M, Dentali F, Duncan J, Gross PL, Kassis J, Kowalski S, Lee AY, Le Gal G, Le Templier G, Li N, MacKay E, Shah V, Shivakumar S, Solymoss S, Spencer FA, Syed S, Tafur AJ, Vanassche T, Thiele T, Wu C, Yeo E, Schulman S. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for Patients on a Direct Oral Anticoagulant Who Need an Elective Surgery or Procedure: Design and Rationale. Thromb Haemost. 2017; 117(12): 2415-2424. [PMID: 29212129]; [DOI: 10.1160/TH17-08-0553]

25. Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013; 368(22): 2113-2124. [PMID: 23718166]; [DOI: 10.1056/NEJMra1206531]

26. Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, Garcia DA, Jacobson A, Jaffer AK, Kong DF, Schulman S, Turpie AG, Hasselblad V, Ortel TL; BRIDGE Investigators. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015; 373(9): 823-833. [PMID: 26095867]; [PMCID: PMC4931686]; [DOI: 10.1056/NEJMoa1501035]


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