Management of Anticoagulation and Antithrombotics

Arjun R. Sondhi, MD

An increasing number of patients require antithrombotics (antiplatelets and/or anticoagulants), which are also increasing in number and complexity, requiring endoscopists to understand the indications, metabolism, bleeding risk, and thrombosis risk surrounding the use and interruption of these medications in low- and high-bleeding-risk procedures. This provides a summary of multiple guidelines, recognizing many of these are based on observational studies or the expert opinion.¹,²,³,⁴ With the growing interest in improving the knowledge base and accessibility to antithrombotic management resources, consider use of a free, validated online tool (www.endoaid.net) to assist in real-time management of antithrombotics.⁵,⁶ This decision support is based on the 2016 American Society of Gastrointestinal Endoscopy (ASGE).

PROCEDURAL RISK

While antithrombotics increase the risk of gastrointestinal (GI) bleeding, there is a large body of evidence supporting their use in a variety of conditions. There are competing interests—maintaining vascular patency with use of these medications but avoiding procedure-related GI bleeding by interrupting the medication. These competing interests have been stratified as low risk and high risk.¹,⁴ An ultra-high-risk category has also been described.³ The main risk factor for periprocedural bleeding is the type of procedure.² The bleeding risk of endoscopy without biopsy or intervention is very low, even in the setting of antithrombotics, but the risk significantly increases with interventions, especially with more invasive endoscopic approaches (e.g., large lesion endoscopic mucosal resection [EMR], per-oral endoscopic myotomy [POEM], and endoscopic submucosal dissection [ESD]). Table 4.1 stratifies procedural bleeding risk.

TABLE 4.1 Bleeding Risk Stratification of Procedures³,⁴

Low Risk	High Risk	Ultra High Risk
Upper or lower endoscopy with or without cold forceps biopsy	Polypectomy	Endoscopic submucosal dissection (ESD)
Endoscopic ultrasound (EUS) without fine needle aspiration (FNA)	ERCP with sphincterotomy	Endoscopic mucosal resection (EMR) of polyps >2 cm
Endoscopic retrograde cholangiopancreatography (ERCP) with or without pancreatobiliary stenting or papillary dilation but without sphincterotomy	Pneumatic or bougie dilation	Per-oral endoscopic myotomy (POEM)
Push or diagnostic balloon-assisted enteroscopy (BAE)	Therapeutic BAE
Video capsule endoscopy	Variceal sclerotherapy or band ligation
Esophageal, enteral, or colonic stenting	Percutaneous endoscopic gastrostomy or jejunostomy
Argon plasma coagulation	EUS with FNA
Barrett’s ablation	Endoscopic hemostasis Tumor ablation Cyst gastrostomy Ampullectomy EMR
From Chan FKL, Goh KL, Reddy N, 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(3):405-417. doi:10.1136/gutjnl-2017-315131. Epub January 13, 2018. Review. PMID: 29331946 and Acosta RD, Abraham NS, Chandrasekhara V, et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016;83(1):3-16. doi:10.1016/j.gie.2015.09.035. Epub November 24, 2015. PMID: 26621548.

THROMBOSIS RISK

Conditions carrying risk of thrombosis or requiring antithrombotics include atrial fibrillation (AF), cardiac valvular replacements, deep vein thrombosis and venous thromboembolism, cerebral artery thrombosis, percutaneous coronary intervention (PCI) or other vascular stenting, acute coronary syndromes, cerebrovascular accident (CVA), transient ischemic attack (TIA), and a genetic or acquired (e.g., malignancy) hypercoaguable state.² Complicating this, the objective measurement of severity of bleeding is difficult.² For example, a 2002 ASGE guideline designated a
procedure as low risk of bleeding if the rate was ≤1.5%,⁷ but this definition is not standardized and has not appeared in later iterations of the ASGE’s antithrombotic guidelines.

Of particular mention is AF, as this is one of the most common reasons for anticoagulation, and the prevalence of this condition increases with age. The CHA₂DS₂-VASc (C2V) score quantifies the risk of AF-related CVA. The C2V score is calculated as a sum of points associated with the below patient attributes:

Congestive heart failure = 1 point
Hypertension = 1 point
Age 75 years or greater = 2 points
Diabetes = 1 point
Stroke or TIA = 2 points
Vascular disease = 1 point
Age 65 to 74 years = 1 point
Sex category (female gender) = 1 point

The annual risk of AF-related CVA generally increases with an increasing C2V score.⁴ A C2V score of ≥2 portends a high risk of stroke and usually warrants systemic anticoagulation.

BLEEDING RISK

Procedure-Related Factors

Table 4.2 provides the risk of bleeding in the absence of antithrombotics.⁸

Patient-Related Factors

In addition to the binary factor of presence versus absence of use of anticoagulant, HAS-BLED is a validated multivariable score in AF patients that was developed to determine the 1-year risk of significant bleeding (intracranial bleeding, hospitalization, hemoglobin decrease >2 grams/deciliter (g/dL), or transfusion) while on anticoagulation⁹ and, compared to other bleeding scoring systems, is the best predictor of bleeding in AF patients.¹⁰ The HAS-BLED score is calculated as a sum of points associated with the below patient attributes, each of which is assigned an equal weight of 1 point⁹:

Hypertension: systolic blood pressure >160 millimeters (mm) of mercury
Abnormal renal function (dialysis, status post renal transplant, or serum creatinine >2.25 milligrams [mg]/dL) or abnormal hepatic function (cirrhosis, total bilirubin >2 times the upper limit of normal [ULN]; or aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase >3 times the ULN)

Stroke: prior history of CVA

TABLE 4.2 Procedure-Related Hemorrhage Risk in Patients Not on Antithrombotics⁸

Procedure	Hemorrhage Risk (%)
Colonic polypectomy	0.07-1.7
Colon EMR of lesion >10 mm	3.7-11.3
Esophageal EMR	0.6-0.9
Duodenal EMR	6.3-12.3
Endoscopic submucosal dissection	2-6.9
ERCP with sphincterotomy	0.1-0.2
ERCP with sphincteroplasty	0.19
Ampullectomy	1-7
Esophageal dilation	0-1.7
Esophageal, duodenal, enteral stent	0.5-1
Colonic stent	0-4.5
Percutaneous endoscopic gastrostomy	≤2
EUS with FNA	0.13
EUS with brushing of pancreas cyst	0-3.3
EMR, endoscopic mucosal resection; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; FNA, fine needle aspiration.
Reprinted by permission from Springer: Veitch AM. Endoscopy in patients on antiplatelet agents and anticoagulants. Curr Treat Options Gastroenterol. 2017;15(2):256-267. Copyright © 2017 Springer Science+Business Media, LLC.

Bleeding: prior major bleeding or other predisposition to bleeding
Labile international normalized ratio (INR): unstable or high INR or INR in the therapeutic range <60% of the time
Elderly: age >65 years
Drug use: prior alcohol use (≥8 drinks per week), prior drug use, antiplatelet agents, or nonsteroidal anti-inflammatory drugs

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