Section II The Patient and Endoscopy

10.1055/b-0038-149312

11 Anticoagulation and Endoscopy

Eduardo Rodrigues-Pinto and Todd H. Baron

11.1 Introduction

Anticoagulation and endoscopy often go hand in hand, and management of antithrombotic therapy in patients undergoing endoscopic procedures can be challenging. The risk of endoscopy in patients on antithrombotics depends on the risks of procedural hemorrhage and thrombosis due to discontinuation of therapy. The decision-making process is challenging when moderate-to high-risk patients, for thrombosis off anticoagulation, undergo high-risk bleeding procedures. Management also differs between elective and emergency procedures. Appropriate decision making requires knowledge of thrombotic risk, procedure-related bleeding risk, concepts of bridging anticoagulation, and timing of cessation and reinitiation of antithrombotic agents. A discussion between clinicians specializing in preoperative management of antithrombotic agents and coagulation disorders, primary providers prescribing these agents, and the proceduralist is essential. Ideally, this communication should occur well in advance of the procedure to increase patient safety and facilitate patient education. In this chapter, we review antiplatelet agents, anticoagulants, procedure risks, assessment of thrombotic risk, antithrombotic management, postprocedure care, and endoscopy procedures in the actively bleeding patient on antithrombotic therapy.

A large number of patients require long-term treatment with anticoagulant and antiplatelet agents (APAs), collectively known as antithrombotic agents. Antithrombotics are prescribed to reduce the risk of thromboembolic complications in patients with certain cardiovascular and thromboembolic conditions. ¹ In addition, dual antiplatelet therapy (DAPT; combination treatment with aspirin and a thienopyridine) after coronary-artery stent placement has dramatically increased. ²

In patients undergoing elective endoscopic procedures in whom the decision is made to discontinue these agents, familiarity with these medications is required to optimize the timing of cessation before, and reinitiation after procedures. The absolute risk of an embolic event in patients whose anticoagulation is interrupted for 4 to 7 days is approximately 1%. ³ In addition to drug cessation, the risk of thromboembolism might be increased by dehydration caused by preparation for endoscopic examinations. ⁴ Similarly, in those patients for whom the decision is made to continue antithrombotic agents for elective procedures, the clinician must understand the risk that these agents impart on procedural-induced bleeding. Finally, it is important to understand how to manage these agents in the setting of urgent/emergent endoscopic procedures and in the presence of acute gastrointestinal bleeding (GIB).

The goal is to minimize thromboembolic events and major hemorrhage in the periprocedural period. For patients taking antithrombotics who require endoscopy, the urgency of the procedure, its bleeding risks, the effect of the antithrombotic drug(s) on the bleeding risk, and the risk of a thromboembolic event related to periprocedural interruption of antithrombotic agents must be considered. ⁵

Although guidelines from major Gastroenterological societies provide a framework for management of antithrombotics, the decision-making process may not always be straightforward. ⁶ , ⁷ , ⁸

11.2 Antithrombotics

11.2.1 Antiplatelet Agents

APAs decrease platelet aggregation, thus preventing thrombus formation. APAs are usually used in patients with ischemic heart disease, coronary stents, and cerebrovascular disease. Aspirin causes irreversible inhibition of the cyclooxygenase 1 and 2 enzyme systems; after cessation of aspirin, 7 to 9 days are required to regain full platelet function. ⁹ Clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Bridgewater, New Jersey, United States), prasugrel (Effient, Eli Lilly and Company, Indianapolis, Indiana, United States), ticlopidine (Ticlid, Roche Pharmaceuticals, Nutley, New Jersey, United States), and ticagrelor (Brilinta, AstraZeneca, Wilmington, Delaware, United States) are thienopyridines, which inhibit the P2Y12 component of the adenosine diphosphate (ADP) receptors, preventing activation of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex. ¹⁰ , ¹¹ Restoration of normal platelet aggregation requires 5 to 7 days for clopidogrel and prasugrel and 3 to 5 days for ticagrelor. Dipyridamole (Persantine, Teva Pharmaceuticals USA, Sellersville, Pennsylvania, United States) reversibly inhibits platelet aggregation; its duration of action is about 2 days after discontinuation. Abciximab (ReoPro, Eli Lilly and Company, Indianapolis, Indiana, United States), eptifibatide (Integrilin, Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, United States), and tirofiban (Aggrastat, Medicure Pharma, Inc, Somerset, New Jersey, United States) are GPIIb/IIIa receptor inhibitors that limit platelet aggregation, respectively, for 24 hours, 4 hours, and 1 to 2 seconds after discontinuation. ¹⁰ , ¹¹

11.2.2 Anticoagulants Agents

Anticoagulants prevent the clotting of blood by interfering with the native clotting cascade. Warfarin (Coumadin, Bristol-My-ers Squibb Company, Princeton, New Jersey, United States) is an oral anticoagulant that inhibits the vitamin K–dependent clotting factors II, VII, IX, and X and proteins C and S. ¹⁰ , ¹¹ Heparin derivatives (unfractionated heparin [UFH] and low-molecular-weight heparin [LMWH]) are administered intravenously and should be administered 4 to 6 hours and 24 hours, respectively, before high-risk procedures. ¹⁰ , ¹¹ Fondaparinux (Arixtra, GlaxoSmithKline, Research Triangle Park, North Carolina, United States) is a specific inhibitor of factor Xa, with anticoagulant effects lasting for at least 36 hours. ¹⁰ , ¹¹ Rivaroxaban (Xarel-to, Janssen Pharmaceuticals, Inc, Raritan, New Jersey, United States), apixaban (Eliquis, Bristol-Myers Squibb Company, Princeton, New Jersey, United States), and edoxaban (Savaysa, Daiichi Sankyo Co, LTD, Tokyo, Japan) are direct factor Xa inhibitors, while dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States), hirudins, and argatroban (Acova, Abbott Laboratories, North Chicago, Illinois, United States) are direct thrombin inhibitors. ¹⁰ , ¹¹ Direct oral anticoagulants (DOACs) reach a maximum effect 1.25 to 3 hours after ingestion and should be discontinued ≥ 48 hours before a high-risk procedure. ¹¹ These agents overcome some of the vitamin K antagonists (VKAs) pitfalls such as their narrow therapeutic window, the need for frequent monitoring, and dose adjustments as well as the interaction with foods and/or other drugs. However, specific antidotes are limited, with only idarucizumab (Praxbind, Boehringer Ingelheim, Inc, Ridgefield, Connecticut, United States) approved for use in cases of life-threatening uncontrolled bleeding or prior to emergency surgery in patients on dabigatran. ¹² Prothrombin time and activated partial thromboplastin time are poor measures of drug effect and are insensitive and often minimally prolonged or normal in spite of therapeutic drug levels. ¹³

Procedure Risks

There is an intrinsic risk of hemorrhage associated with endoscopic procedures. Hemorrhage may be immediately apparent at the time of endoscopy or may be delayed for up to 2 weeks following the procedure.

In general, a patient undergoing a procedure associated with low risk of bleeding (low-risk procedure) can (and should) safely continue antithrombotic therapy, particularly if the patient is at high risk for a thromboembolic event (high-risk patient). ¹ Conversely, a patient undergoing a high-risk procedure can temporarily discontinue antithrombotic agents safely if the patient is at low risk for a thromboembolic event (low-risk patient). ¹ The decision-making process is challenging when patients at moderate-to-high risk for thromboembolic events undergo high-risk procedures. Management also differs between elective and emergency procedures. ¹ Elective endoscopic procedures should be deferred until short-term anticoagulation therapy is completed.

Common endoscopic procedures vary in their potential to induce bleeding (▶Table 11.1). ⁴ , ¹¹ , ¹⁴ Studies on postprocedural bleeding risks have been conducted in patients who are not on antithrombotic regimens and thus may not accurately reflect the bleeding risk of patients using antithrombotic therapies.

**Table 11.1** Risk stratification of endoscopic procedures based on the risk of hemorrhage
Low risk	High risk
Diagnostic procedures including mucosal biopsy	Endoscopic polypectomy
ERCP with stent placement or papillary balloon dilation without sphincterotomy	ERCP with sphincterotomy or large balloon papillary dilation
Device-assisted enteroscopy without polypectomy	Endoscopic hemostasis
Capsule endoscopy	Ampullectomy
Enteral stent deployment ^a (controversial)	EMR or ESD
EUS without FNA	Endoscopic dilatation of strictures
Argon plasma coagulation	Endoscopic therapy of varices
Barrett’s ablation	PEG ^b /PEJ
	EUS with FNA ^c
	EUS-guided biliary drainage
	Transmural drainage procedures (e.g., pancreatic fluid collections, gallbladder drainage)
	Tumor ablation
Abbreviations: EMR, endoscopic mucosal resection; ERCP, endoscopic retrograde cholangiopancreatography; ESD, endoscopic submucosal dissection; EUS, endoscopic ultrasound; FNA, fine-needle aspiration; PEG/PEJ: percutaneous endoscopic gastrostomy/jejunostomy
^aEnteral stent deployment risk is controversial for American Society for Gastrointestinal Endoscopy (ASGE), low risk for Japanese guidelines, and high risk for European Society for Gastrointestinal Endoscopy (ESGE).
^bPEG on aspirin or clopidogrel therapy is low risk for ASGE, but high risk for ESGE and Japanese guidelines; does not apply to dual antiplatelet therapy.
^cEUS-FNA of solid masses on acetylsalicylic acid/nonsteroidal anti-inflammatory drugs is low risk.