An algorithmic approach to gastrointestinal bleeding in patients receiving antithrombotic agents
Gastroenterology and Hepatology from Bed to Bench,
,
9 December 2020
https://doi.org/10.22037/ghfbb.v13i1.2189
Abstract
Introduction: Gastrointestinal bleeding is an overwhelming complication of patients taking antithrombotic agents. These drugs pose a challenge to physicians in the management of bleeding to establish hemostasis without putting these patients at a higher risk for thromboembolism. This study aims to propose an algorithmic approach to four major groups of patients receiving antithrombotic agents (single antiplatelet agents, dual antiplatelet agents, anticoagulants and direct oral anticoagulants) to decide when and how these drugs should be held or restarted to offset between the risk of re-bleeding and thromboembolism. Case presentation: Four case-based algorithms are proposed in this article based on some relevant articles. Having designed four case-based algorithms, we are hoping to guide physicians who face a dilemma on the management of patients receiving antithrombotics when gastrointestinal bleeding occurs. Results: Patients using antithrombotics referred for gastrointestinal bleeding were stratified into four groups based on the medication which is used as an antithrombotic agent and four algorithms were designed which are presented here. We have made an attempt to have a stepwise approach to four cases relevant to the study and have an evaluation on the management of their antithrombotic agents during an episode of gastrointestinal bleeding. Conclusion: literally, It is widely accepted that antithrombotic agents be restarted as soon as possible after establishment of hemostasis in a patient taking antithrombotics referring for gastrointestinal bleeding. The time for reinitiating of these drugs would be different based on the severity of bleeding, the probability of thromboembolic events as well as the nature of the antithrombotic medication which is used by the patient.
Key words: Algorithms, Gastrointestinal bleeding; Thromboembolic events; Antithrombotic agents
Keywords:
- Algorithms, Gastrointestinal bleeding; Thromboembolic events; Antithrombotic agents
References
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6. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2017;39(3):213–60.
7. Acosta R.D, Abraham N.S, Chandrasekhara V et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointestinal Endoscopy. 2016;83:3–16.
8. Gralnek I, Dumonceau J, Kuipers E, Lanas A et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. 2015;47:a1–a46.
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10. Abraham N.S, Hlatky M.A, Antman E.M et al. expert consensus document ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks. Circulation. 2010;122:2619–2633.
11. Sung J.J.Y, Lau J.Y.W, Ching J.Y.L et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding a randomized trial. Annals of Internal Medicine. 2010;152:1–9.
12. Halvorsen S, Storey RF, Rocca B, et al. Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: expert consensus paper of the European Society of Cardiology Working Group on Thrombosis. Eur Heart J. 2017;38(19):1455–62.
13. Strate LL, Gralnek IM. ACG clinical guideline: management of patients with acute lower gastrointestinal bleeding. Am J Gastroenterol. 2016;111(4):459–74.
14. Yoshihiko Saito, Sadanori Okada, Hisao Ogawa et al. Low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus: 10-year follow up of a randomized controlled trial. Circulation. 2017;135(7):659-670.
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16. Veitch A, Vanbiervliet G, Gershlick T 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;65:374–389.
17. Ray WA, Chung CP, Murray KT, et al. Association of proton pump inhibitors with reduced risk of warfarin-related serious upper gastrointestinal bleeding. Gastroenterology. 2016;151(6):1105–1112.e10.
18. Yusuf S, Zhao F, Mehta S. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. New England Journal of Medicine. 2001;345:494–502.
19. Zakko L, Rustagi T, Douglas M, and Laine L. No benefit from platelet transfusion for gastrointestinal bleeding in patients taking antiplatelete agents. Clin gastroenterol hepatol. 2017;15(1):46-52.
20. Witt DM, Delate T, Garcia DA, et al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med. 2012;172(19):1484–91.
21. Qureshi W, Mittal C, Patsias I et al. Restarting anticoagulation and outcomes after major gastrointestinal bleeding in atrial fibrillation. The American Journal of Cardiology. 2014;113:662–668.
22. Tapaskar N, Pang A, Werner D. A, Sengupta N. Resuming anticoagulation following hospitalization for gastrointestinal bleeding is associated with reduced thromboembolic events and improved mortality: results from a systematic review and meta-analysis. Dig. Dis. Sci. 2020.
23. Granger C.B, Alexander J.H, McMurray J.J et al apixaban versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine. 2011;365:981–992.
24. Nagata N, Sakurai T, Moriyasu S, Shimbo T, Okubo H, Watanabe K. Impact of INR monitoring, reversal agent use, heparin bridging, and anticoagulant interruption on re-bleeding and thromboembolism in acute gastrointestinal bleeding. PLoS One. 2017;12(9):e0183423.
25. Giugliano R.P, Ruff C.T, Braunwald E. Edoxaban versus warfarin in patients with atrial fibrillation. New England Journal of Medicine. 2013;369:2093–2104.
26. Francesco Dentali, Chiara Marchesi, Matteo Giorgi Pierfranceschi et al. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb Haemost. 2011;106(3):429-438.
27. Abraham N.S, Singh S, Alexander G.C, Heien H et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. The British Medical Journal. 2015;350:h1857.
28. Patel RJ, Witt DM, Saseen JJ, Tillman DJ, Wilkinson DS. Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation. Pharmacotherapy. 2000;20(10):1159-1166.
29. Desai J, Kolb J.M, Weitz J.I and Aisenberg J. Gastrointestinal bleeding with the new oral anticoagulants – defining the issues and the management strategies. Thrombosis and Hemostasis. 2013;110:205–212.
30. Diep R, Garcia D. Should we monitor the direct oral anticoagulants? J throm thrombolysis 2020;(50):30-32.
31. Connolly S.J, Ezekowitz M.D, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine. 2009;361:1139–1151.
32. Patel M.R, Mahaffey K.W, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. The New England Journal of Medicine. 2011;365:883–891.
33. Xiaoping Xu and Qian Liang. Dabigatran monitoring was influencec by thrombin time reagent with different thrombin concentrations. Clin Appl Thromb Hemost. 2019;25:1076029619867137.
34. Halvorsen S, Atar D, Yang H et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. European Heart Journal. 20014;35:1864–1872.
35. Ikeda K, and Tachibana H. J arrhythm. Clinical implicatio of monitoring rivaroxaban and apixaban by using anti-factor Xa assay in patients with non-valvular atrial fibrillation. 2016;32(1):42-50.
36. Erenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR and Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, cross over study in healthy subjects. Circulation. 2011;124(14):1573-1579.
37. Charles V. Pollack, Paul A. Reilly, Joanne van Ryn et al. Idarucizumab for dabigatran reversal-full cohort analysis. N Engl J Med. 2017;377:431-441.
38. Giuseppe Marano, Stefania Vaglio, Simonetta Pupella, Giancarlo M. Liumbruno and Massimo Franchini. How we treat bleeding associated with direct oral anticoagulants. Blood transfus. 2016;14(5):465-473.
39. Khadzhynov D, Wagner F, Formella S et al. Effective elimination of dabigatran by hemodialysis. A phase I single-center study in patients with end stage renal disease. Thromb Haemost. 2013;109(4):596-605.
40. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–962.
41. Rottenstreich A, Zacks N, Kleinstern G, Raccah BH, Roth B, Da’as N, Kalish Y (2018) Direct-acting oral anticoagulant drug level monitoring in clinical patient management. J Thromb Thrombol 45:543–549.
42. Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S (2016) Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 14:1308–1313.
43. Moll S, Martin KA (2018) Anticoagulant drug choice in patients who have had bariatric surgery—presently, DOACs are not the preferred choice. Thromb Res 163:196–199.
44. Hein Heidbuchel, Peter Verhamme, Marco Alings et al. Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. EP Europace. 2013;15(5):625-651.
45. Elhosseiny S, Moussawi H. A, Chalhoub J. M, Lafferty J, and Deeb L. Direct oral anticoagulants in cirrhotic patients: current evidence and clinical observations. Can J Gastroenterol hepatol. 2019;4383269.
46. Sharifian A, Tavakoli E, Ashtari S and Zali M. R. Endoscopic findings in upper gastrointestinal bleeding patients at Tehran’s Taleghani Hospital, Iran. Govaresh 2016;21(4):260-265.
2. Gimbel M. E, Minderhoud S. C. S and Berg J. M. ten. A practical guide on how to handle patients with bleeding events while on oral antithrombotic treatment. Neth Heart J (2018) 26:341–351.
3. Patsias I, Mittal C, Elbatta M, et al. Optimal duration to restart warfarin after discontinuation of therapy in atrial fibrillation patients that developed gastrointestinal bleeding. Journal of the American College of Cardiology. 2013;61: E342.
4. Gage BF, Waterman AD, Shannon W, Rich MW and Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation. JAMA 2001;285(22):2864-70.
5. Lee J.K, Kang H.W, Kim S.G, Kim J.S and Jung H.C. Risks related with withholding and resuming anticoagulation in patients with non-variceal upper gastrointestinal bleeding while on warfarin therapy. International Journal of Clinical Practice.2012;66:64–68.
6. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2017;39(3):213–60.
7. Acosta R.D, Abraham N.S, Chandrasekhara V et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointestinal Endoscopy. 2016;83:3–16.
8. Gralnek I, Dumonceau J, Kuipers E, Lanas A et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. 2015;47:a1–a46.
9. Francis K L Chan, Khean-Lee Goh, Nageshwar Reddy 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;67:405-417.
10. Abraham N.S, Hlatky M.A, Antman E.M et al. expert consensus document ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks. Circulation. 2010;122:2619–2633.
11. Sung J.J.Y, Lau J.Y.W, Ching J.Y.L et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding a randomized trial. Annals of Internal Medicine. 2010;152:1–9.
12. Halvorsen S, Storey RF, Rocca B, et al. Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: expert consensus paper of the European Society of Cardiology Working Group on Thrombosis. Eur Heart J. 2017;38(19):1455–62.
13. Strate LL, Gralnek IM. ACG clinical guideline: management of patients with acute lower gastrointestinal bleeding. Am J Gastroenterol. 2016;111(4):459–74.
14. Yoshihiko Saito, Sadanori Okada, Hisao Ogawa et al. Low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus: 10-year follow up of a randomized controlled trial. Circulation. 2017;135(7):659-670.
15. Souk M. K, Tamim M. H, Daya A Abu H, Rockey D. C, and Barada K. A. Aspirin use for primary prophylaxis: Adverse outcomes in non-variceal upper gastrointestinal bleeding. World J Gastrointest Surg. 2016;8(7):501-507.
16. Veitch A, Vanbiervliet G, Gershlick T 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;65:374–389.
17. Ray WA, Chung CP, Murray KT, et al. Association of proton pump inhibitors with reduced risk of warfarin-related serious upper gastrointestinal bleeding. Gastroenterology. 2016;151(6):1105–1112.e10.
18. Yusuf S, Zhao F, Mehta S. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. New England Journal of Medicine. 2001;345:494–502.
19. Zakko L, Rustagi T, Douglas M, and Laine L. No benefit from platelet transfusion for gastrointestinal bleeding in patients taking antiplatelete agents. Clin gastroenterol hepatol. 2017;15(1):46-52.
20. Witt DM, Delate T, Garcia DA, et al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med. 2012;172(19):1484–91.
21. Qureshi W, Mittal C, Patsias I et al. Restarting anticoagulation and outcomes after major gastrointestinal bleeding in atrial fibrillation. The American Journal of Cardiology. 2014;113:662–668.
22. Tapaskar N, Pang A, Werner D. A, Sengupta N. Resuming anticoagulation following hospitalization for gastrointestinal bleeding is associated with reduced thromboembolic events and improved mortality: results from a systematic review and meta-analysis. Dig. Dis. Sci. 2020.
23. Granger C.B, Alexander J.H, McMurray J.J et al apixaban versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine. 2011;365:981–992.
24. Nagata N, Sakurai T, Moriyasu S, Shimbo T, Okubo H, Watanabe K. Impact of INR monitoring, reversal agent use, heparin bridging, and anticoagulant interruption on re-bleeding and thromboembolism in acute gastrointestinal bleeding. PLoS One. 2017;12(9):e0183423.
25. Giugliano R.P, Ruff C.T, Braunwald E. Edoxaban versus warfarin in patients with atrial fibrillation. New England Journal of Medicine. 2013;369:2093–2104.
26. Francesco Dentali, Chiara Marchesi, Matteo Giorgi Pierfranceschi et al. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb Haemost. 2011;106(3):429-438.
27. Abraham N.S, Singh S, Alexander G.C, Heien H et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. The British Medical Journal. 2015;350:h1857.
28. Patel RJ, Witt DM, Saseen JJ, Tillman DJ, Wilkinson DS. Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation. Pharmacotherapy. 2000;20(10):1159-1166.
29. Desai J, Kolb J.M, Weitz J.I and Aisenberg J. Gastrointestinal bleeding with the new oral anticoagulants – defining the issues and the management strategies. Thrombosis and Hemostasis. 2013;110:205–212.
30. Diep R, Garcia D. Should we monitor the direct oral anticoagulants? J throm thrombolysis 2020;(50):30-32.
31. Connolly S.J, Ezekowitz M.D, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine. 2009;361:1139–1151.
32. Patel M.R, Mahaffey K.W, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. The New England Journal of Medicine. 2011;365:883–891.
33. Xiaoping Xu and Qian Liang. Dabigatran monitoring was influencec by thrombin time reagent with different thrombin concentrations. Clin Appl Thromb Hemost. 2019;25:1076029619867137.
34. Halvorsen S, Atar D, Yang H et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. European Heart Journal. 20014;35:1864–1872.
35. Ikeda K, and Tachibana H. J arrhythm. Clinical implicatio of monitoring rivaroxaban and apixaban by using anti-factor Xa assay in patients with non-valvular atrial fibrillation. 2016;32(1):42-50.
36. Erenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR and Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, cross over study in healthy subjects. Circulation. 2011;124(14):1573-1579.
37. Charles V. Pollack, Paul A. Reilly, Joanne van Ryn et al. Idarucizumab for dabigatran reversal-full cohort analysis. N Engl J Med. 2017;377:431-441.
38. Giuseppe Marano, Stefania Vaglio, Simonetta Pupella, Giancarlo M. Liumbruno and Massimo Franchini. How we treat bleeding associated with direct oral anticoagulants. Blood transfus. 2016;14(5):465-473.
39. Khadzhynov D, Wagner F, Formella S et al. Effective elimination of dabigatran by hemodialysis. A phase I single-center study in patients with end stage renal disease. Thromb Haemost. 2013;109(4):596-605.
40. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–962.
41. Rottenstreich A, Zacks N, Kleinstern G, Raccah BH, Roth B, Da’as N, Kalish Y (2018) Direct-acting oral anticoagulant drug level monitoring in clinical patient management. J Thromb Thrombol 45:543–549.
42. Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S (2016) Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 14:1308–1313.
43. Moll S, Martin KA (2018) Anticoagulant drug choice in patients who have had bariatric surgery—presently, DOACs are not the preferred choice. Thromb Res 163:196–199.
44. Hein Heidbuchel, Peter Verhamme, Marco Alings et al. Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. EP Europace. 2013;15(5):625-651.
45. Elhosseiny S, Moussawi H. A, Chalhoub J. M, Lafferty J, and Deeb L. Direct oral anticoagulants in cirrhotic patients: current evidence and clinical observations. Can J Gastroenterol hepatol. 2019;4383269.
46. Sharifian A, Tavakoli E, Ashtari S and Zali M. R. Endoscopic findings in upper gastrointestinal bleeding patients at Tehran’s Taleghani Hospital, Iran. Govaresh 2016;21(4):260-265.
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