Gastroenterological Endoscopy. Группа авторов

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.

      Assessment of Thrombotic Risk

      The probability of a thromboembolic event related to the temporary interruption of antithrombotic therapy for an endoscopic procedure depends on the indication for antithrombotic therapy and individual patient characteristics (

Table 11.2).^4,11,14

      Antiplatelet Agents Management

      While the American Society for Gastrointestinal Endoscopy (ASGE) recommends continuation of low-dose aspirin and nonsteroidal anti-inflammatory drugs in the periendoscopic period,¹¹ the European Society for Gastrointestinal Endoscopy (ESGE) recommends continuing aspirin for all endoscopic procedures, with the exception of endoscopic submucosal dissection, large colonic endoscopic mucosal resection (EMR) (>2 cm), upper GI EMR, and ampullectomy (

Table 11.3).¹⁴ In the latter cases, aspirin discontinuation should be considered on an individual-patient basis depending on thrombosis and hemorrhage risks.¹⁴ Japanese guidelines consider withdrawal of aspirin monotherapy in high-risk endoscopic procedures for 3 to 5 days in patients at low risk of thromboembolism; aspirin monotherapy should be continued in patients at high risk of thromboembolism.⁴ In patients on long-term low-dose aspirin for secondary prevention, aspirin interruption was associated with a three times increased risk of cardiovascular or cerebrovascular events, and 70% of these events occurred ≤ 7 to 10 days after interruption.¹⁵ For low-risk endoscopic procedures, thienopyridines should be continued, as single or DAPT.^11,14 For high-risk endoscopic procedures in patients at low thrombotic risk, thienopyridines should be discontinued 5 days (if taken as monotherapy) to 7 days (if taken as DAPT) before the procedure.⁴ In patients on DAPT, aspirin should be continued.^11,14 For high-risk endoscopic procedures in patients at high thrombotic risk, when it is not feasible to withdraw thienopyridines, replacement with aspirin should be performed after consultation with the prescribing doctor.^4,11,14

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 deploymenta (controversial)	EMR or ESD
EUS without FNA	Endoscopic dilatation of strictures
Argon plasma coagulation	Endoscopic therapy of varices
Barrett’s ablation	PEGb/PEJ
	EUS with FNAc
	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.

Table 11.2 Risk stratification for discontinuation of clopidogrel, prasugrel, or ticagrelor, and warfarin therapy based on risk of thrombosis and consideration of need for bridge therapy

Low risk	High risk
Clopidogrel, prasugrel, or ticagrelor
Ischemic heart disease without coronary stents	Drug-eluting coronary artery stents within 12 months of placement
Cerebrovascular disease	Bare metal coronary artery stents within 1 month of placement
Peripheral vascular disease
Warfarin
Prosthetic metal heart valve in aortic position	Prosthetic metal heart valve in mitral position
Xenograft heart valve	Prosthetic heart valve and atrial fibrillation
Atrial fibrillation without valvular disease	Atrial fibrillation and mitral stenosisa
> 3 months after venous thromboembolism	< 3 months after venous thromboembolism
Thrombophilia syndromes
a Uncertainty exists regarding