Anticoagulants Agents Management
Warfarin should be continued for low-risk endoscopic procedures (
Although all guidelines recommend bridging therapy for patients with high thromboembolic risk requiring temporary withdrawal of anticoagulants, a recent meta-analysis of 35 studies found an increased risk of overall and major bleeding but a similar thromboembolic risk in patients receiving periprocedural heparin-bridging therapy.16,17 Thus, caution should be taken to balance the benefits of bridging therapy and the risks of bleeding in patients needing temporary discontinuation of anticoagulant. All patients on warfarin should be advised that there is an increased risk of postprocedure bleeding compared to nonanticoagulated patients, even when temporarily discontinued.11,14 In a multivariate analysis, however, most bleeding was immediate and successfully treated endoscopically without significant consequence.18 Hemorrhage secondary to high-risk endoscopic procedures can often be controlled by further endoscopic therapeutic measures, and is rarely fatal. Thrombotic adverse events such as stroke from interruption of anticoagulation can be catastrophic.19
Postendoscopic Procedure
If APAs or anticoagulants are discontinued, there is consensus that antithrombotic therapy should be resumed upon completion of the procedure. Warfarin should be restarted within 24 hours of the procedure in patients with valvular heart disease and a low risk for thromboembolism; in patients at high risk for thromboembolism, UFH or LMWH should be restarted as soon as “bleeding stability allows” and continued until the INR reaches an appropriate therapeutic level.20 UFH may be restarted 2 to 6 hours after a therapeutic procedure. The optimal time to restart LMWH after endoscopy has not been determined. Delaying reinitiation of LMWH 48 to 72 hours after surgery should be considered in patients believed to be at high risk for bleeding adverse events.2 There are no data regarding optimal timing of resumption of DOACs after endoscopic procedures. If they cannot be restarted within 24 hours after a high-risk procedure, then bridge therapy should be considered for patients at high risk for thromboembolism.21,22 Reinitiation of DOACs should be delayed for at least 48 hours after high-risk procedures because full anticoagulation occurs shortly after administration; for patients in whom biliary sphincterotomy is performed, resumption of these agents should be delayed for at least 72 hours; for patients who are at high risk of delayed bleeding and who are at low risk for antithrombotic events, it would be reasonable to hold anticoagulation for 7 days.23 APAs should be resumed once hemostasis has been achieved. Clopidogrel administered at maintenance doses has delayed onset and can be reinitiated within 24 hours; clopidogrel loading results in rapid onset of action and should be considered among patients at risk for thrombosis with a lower risk of bleeding than anticipated; other APAs, including aspirin, can be reinitiated within 24 hours.
Endoscopy Procedures in the Actively Bleeding Patient on Antithrombotic Therapy
Endoscopic evaluation and therapy in patients using antithrombotics with active GIB is both warranted and safe.5 The decision to stop, reduce, and/or reverse antithrombotic therapy (and thereby risking thromboembolic consequences) must be weighed against the risk of continued bleeding. Reversal of anticoagulation with four-factor prothrombin complex concentrate (PCC) rather than fresh-frozen plasma should be used for patients with VKA-associated major bleeding, in addition to intravenous vitamin K.24 Vitamin K should not be given routinely in patients with mechanical valves because this may create a hypercoagulable condition.25 However, endoscopic hemostatic therapy is very effective even in patients with moderately elevated INR, and it should not be postponed to correct coagulopathy in patients with an INR < 2.5, as normalizing the INR does not reduce re-bleeding. Patients who require anticoagulation after endoscopic therapy receive UFH because of its relatively shorter half-life after successful endoscopic hemostasis for high-risk stigmata.
Regarding the new DOACs in patients with severe GIB, hemodialysis can be used in patients receiving dabigatran but not for rivaroxaban, edoxaban, and apixaban because of their decreased renal excretion and because they are highly protein bound. Charcoal hemoperfusion also may be effective.25 Although factor VIIa and four-factor PCC have been used in these situations, their value in reversing the clinical anticoagulant effects and controlling clinical hemorrhage is uncertain.26
For patients on APAs with life-threatening or serious bleeding, options include stopping these agents and/or administration of platelets. Consultation with the prescribing specialist should occur in situations of significant GIB in patients with high risk for thrombosis. The risk of an adverse cardiac event associated with cessation of the APA therapy likely exceeds the benefit of decreasing postendoscopic bleeding.
References
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[2] Douketis JD, Spyropoulos AC, Spencer FA, et al; American College of Chest Physicians. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2, Suppl):e326S–e350S
[3] Garcia DA, Regan S, Henault LE, et al. Risk of thromboembolism with short-term interruption of warfarin therapy. Arch Intern Med. 2008; 168(1):63–69
[4] Fujimoto K, Fujishiro M, Kato M, et al; Japan Gastroenterological Endoscopy Society. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc. 2014; 26(1):1–14
[5] Abraham NS, Castillo DL. Novel anticoagulants: bleeding risk and management strategies. Curr Opin Gastroenterol. 2013; 29(6):676–683
[6] Tang RS, Chan FK. Prevention of gastrointestinal events in patients on antithrombotic therapy in the peri-endoscopy period: review of new evidence and recommendations from recent guidelines. Dig Endosc. 2015; 27(5):562–571
[7] Anderson MA, Ben-Menachem T, Gan SI, et al; ASGE Standards of Practice Committee. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc. 2009; 70(6):1060–1070
[8] Boustière C, Veitch A, Vanbiervliet G, et al; European Society of Gastrointestinal Endoscopy. Endoscopy and antiplatelet agents. Endoscopy. 2011; 43(5):445–461
[9] Patrono C, Ciabattoni G, Patrignani P, et al. Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation. 1985; 72(6):1177–1184
[10] Di Minno A, Spadarella G, Prisco D. et al. Antithrombotic drugs, patient characteristics, and gastrointestinal bleeding: clinical translation and areas of research. Blood Rev. 2015; 29(5):335–343
[11] Acosta RD, Abraham NS, Chandrasekhara V, et al; ASGE Standards