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UPDATE ON GI BLEEDING
Audio-Digest Gastroenterology
Volume 27, Issue 13
July 7, 2013

Managing Antiplatelet and Anticoagulant agents – Christopher J. Gostout, MD
Managing Upper GI Perforations – Laith H. Jamil, MD
Peptic Ulcer Disease and Upper GI Bleeding – Richard J. Saad, MD

  
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The following is an abstracted summary, not a verbatim transcript, of the lectures/discussions on this audio program.

Gastroenterology Program Info  Accreditation InfoCultural & Linguistic Competency Resources

Update on GI Bleeding

Educational Objectives

The goal of this program is to improve the management of patients who have or are at risk for GI bleeding. After hearing and assimilating this program, the clinician will be better able to:

1. Assess the risk level of endoscopic procedures for patients taking antithrombotic agents.

2. Determine when bridge therapy with unfractionated heparin is indicated.

3. Manage patients with esophageal perforation.

4. Survey the risks factors associated with upper GI bleeding.

5. Implement prevention techniques for patients at risk for GI bleeding.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Saad receives grant support from Takeda Pharmaceuticals North America. Drs. Gostout and Jamil and the planning committee reported nothing to disclose. In his lecture, Dr. Saad presents information that is related to the off-label or investigational use of a therapy, product, or device.

Managing Antiplatelet and Anticoagulant agents

Christopher J. Gostout, MD, Professor of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, MN

Introduction: warfarin (Coumadin, Jantoven, Marevan) widely used, front-line medication; unfractionated heparin (UFH) has become drug of choice for bridge therapy; studies have reported thromboembolisms after taking low molecular weight heparin (LMWH); considerations — urgency of procedure; risk for bleeding related solely to antithrombotic therapy and risk for bleeding related to procedure; risk associated with continuing or discontinuing antithrombotic therapy; risk for thromboembolic event related to interrupting antithrombotic therapy (most severe sequelae of management related to this); interrupting antithrombotic therapy may result in thromboembolic events; consider alternative diagnostic studies and therapies

Recommendations before procedures: from American Society of Gastrointestinal Endoscopy (ASGE); elective procedures — no need for patient to discontinue aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) before elective procedures; abstain from anticoagulant drugs and thienopyridines drugs (clopidogrel and ticlodipine) before elective procedure; urgent procedures — reverse action of all antiplatelet agents with transfusion of fresh platelets; reverse effects of warfarin using fresh frozen plasma (FFP); consider use of vitamin K and protamine sulfate

Procedural risks: procedures with high risk for bleeding — polypectomy; treatment of varices; endoscopic hemostasis (high risk for rebleeding); pearl — risk for clinically significant rebleeding after endoscopic procedures declines dramatically at 96 hr postprocedure; procedures with low risk for bleeding — deployment of enteral stent

Condition risks: conditions associated with high risk for procedural bleeding — patients with atrial fibrillation (AF) associated with valvular heart disease, prosthetic heart valves, active congestive heart failure (CHF), left ventricular ejection fraction <35%, history of thromboembolic events, hypertension and diabetes when associated with AF and valve disease, and advanced age; mechanical valve in mitral position; low-flow state; conditions associated with low risk for procedural bleeding — uncomplicated or paroxysmal nonvalvular AF; bioprosthetic valve; mechanical aortic valve; deep venous thrombosis (DVT); pearl — patients requiring hemostasis considered high risk for rebleeding, regardless of risk of initial procedure or risk of preexisting condition; bleeding after high-risk procedures rarely associated with major morbidity or mortality; conditions associated with high thromboembolic risk — patients with drug-eluting coronary stents (DECS; particularly those with DECS on dual antiplatelet therapy discontinued <12 mo from stent placement); patients with AF and underlying dilated cardiomyopathy, valvular heart disease, or recent thromboembolic events; 5% risk for stroke if antithrombotic drugs not resumed

Stopping before endoscopy: if patient temporarily on antithrombotics for DVT, thrombophlebitis, or pulmonary embolism, delay endoscopy until end of therapy; do not give vitamin K for elective procedures (difficult to restart antithrombotic therapy after vitamin K); for low-risk patients having elective endoscopy, stop warfarin without bridge therapy; inform patient that risk for thrombolic event 1% over 7 days; reinstitute warfarin on day of procedure at usual daily dose and usual time of day; in pregnant woman with artificial valve, delay elective endoscopy until after delivery

Bridge therapy: UFH becoming drug of choice for bridge therapy because of short duration of action, multiple routes of administration (intravenously [IV] or subcutaneously); life-threatening thromboembolism reported in patients on LMWH with artificial valves; bridge therapy discontinued 4 to 6 hr before procedure resumed 2 hr to 6 hr after procedure

Restarting antithrombotic drugs: polypectomy associated with increased bleeding risk during first week when warfarin therapy resumed immediately after procedure; sphincterotomy associated with increased bleeding risk during 3 days after warfarin therapy resumed; percutaneous endoscopic gastrostomy (PEG) has 2.5% overall risk for bleeding, but risk unknown for patient on antithrombotic therapy who receives PEG

Warfarin before elective endoscopy: AF — in patients with no underlying associated condition, discontinue warfarin 3 to 5 days before procedure (no need to check international normalized ratio [INR]) and restart within 24 hr after procedure at patient’s usual daily dose; mechanical valves, history of stroke, or history of embolism — stop warfarin, monitor INR, and start UFH bridge therapy when INR drops below 2 ; stop UFH 4 to 6 hr before procedure and restart 2 to 6 hr after procedure; in high risk patients, warfarin restarted on day of procedure and used concomitantly with UFH until INR reaches therapeutic level; bridge agent stopped once INR becomes therapeutic and time window for thromboembolism has passed; patient with aortic valve — stop warfarin 2 days before procedure; target INR<1.5; restart warfarin in 24 hr

Resumption of antithrombotic drugs after endoscopic hemostasis: if patients used aspirin before procedure, resume aspirin after procedure, but start concomitant use of proton pump inhibitor (PPI); aspirin reinstituted 3 to 5 days after bleeding episode; patients recovering from GI bleeding who previously took thienopyridine should be transitioned to aspirin; warfarin should be resumed 4 to 15 days after endoscopic hemostasis; place patient on IV UFH bridge therapy if concerned about thromboembolic events

Acute coronary syndrome (ACS), vascular stents, and acute cerebrovascular events: patients should receive uninterrupted dual antiplatelet therapy (DAT) for 30 days after implantation of bare-metal stent and for 12 mo after placement of drug-eluting stent; premature discontinuation of DAT contraindicated; patients who receive DAT have 3-fold greater risk for upper GI bleeding, compared with those on single-drug antiplatelet therapy; patients hospitalized with ACS have 1% to 3% risk for upper GI bleeding and 4- to 7-fold increased mortality; delay elective procedure or stop one antithrombotic drug (substitute aspirin for thienopyridine); use aspirin if both drugs stopped; complication risk 1% to 2% for urgent procedures where all antithrombotic drugs discontinued; if ACS occurs after GI bleeding, patients do fairly well; intervene endoscopically as needed, with less concern about antithrombotic drugs; outcomes better if endoscopy performed before catheterization

Overall management schemes: continue aspirin and NSAIDs for all endoscopic procedures, regardless of patient’s bleeding risk; thienopyridines may be continued in patients with low bleeding risk; patients with high bleeding risk and low thromboembolic risk should discontinue use of thienopyridines 7 to 10 days before endoscopy; patients on DAT should discontinue thienopyridine and take aspirin instead; patients with high bleeding and thromboembolic risk should take aspirin therapy; consider stopping therapy 7 to 10 days before endoscopy; patients with high bleeding risk should discontinue warfarin and start bridge therapy before endoscopy

Managing Upper GI Perforations

Laith H. Jamil, MD, Associate Director of Interventional Endoscopy, Cedars-Sinai Medical Center, Los Angeles, CA

Traumatic esophageal perforation (TEP): most patients with TEP have no signs or symptoms; 7% have dysphagia; 19% have subcutaneous emphysema; study performed esophagogastroduodenoscopy (EGD) on patients suspected of having penetrating esophageal injury and found that EGD ruled out esophageal perforation in 89% of patients; EGD 100% sensitive and 92% specific for esophageal perforation

Case 1: woman aged 87 yr who recently had EGD and gastric polypectomy; patient began vomiting blood and had rectal bleeding after returning home; brought to emergency department with abdominal pain; admitted to intensive care unit; endoscopy revealed small esophageal perforation that was increasing in size; Boerhaave syndrome — symptoms include retching, vomiting, excruciating pain, odynophagia, tachypnea, and dyspnea, leading to shock; chest x ray often reveals abnormality (free air); usually diagnosed with computed tomography (CT), or with esophagogram (water-soluble contrast); performing EGD in these patients may make condition worse and delays in care, surgery performed for patient with free perforation; conservative management (eg, suction, antibiotics) has role, especially if perforation contained; endoscopy for patients who may not be good surgical candidates; self-expandable plastic or metal stents reportedly work well for some

Management of perforation: endoscopic clips — earliest treatment for esophageal perforation; study found that “clipping” acute esophageal perforations had median healing time of 5 days; clips less effective for perforations that have existed for long periods; stents — study found that endoscopic stenting had clinical success rate of 85% in patients with benign rupture or anastomotic leak; study found no difference in efficacy among self-expandable plastic stents, fully covered metal stents, or partially covered (PC) metal stents; plastic expandable stents must be left in for 8 wk; metal stents must be left in for 6 wk; study found that 33% of patients had minor stent-related complications (stent migration most common); another study found that 10% of stent removals had procedure-related adverse events, 2% had major adverse events; PC metal stent had highest risk for complication during removal; no association between amount of time that patient had stent in place and how embedded stent was; removal of PC stents — PC stents difficult to remove; study placed expandable plastic stent proximal to PC stent to make removal of PC stent easier; plastic stent put in place for 1 to 3 wk; placement of proximal stent had 96% success rate for removal of PC stent with minimal complications; indications — esophageal fistula main indication for use of stents in research; success of stent placement depended on type of fistula; study found that anchoring stent with endoscopic clip decreases likelihood of stent migration; gastric sleeve leak — study of 9 patients with gastric staple line leak; authors used fully covered stents, proximal end placed 5 to 7 cm above fistula; clips used as well; mean stent treatment duration of 6.4 wk, but some patients had stent for 17 wk; 78% success rate with stents alone

Iatrogenic perforation: study of patients with acute esophageal, gastric, duodenal, and colonic perforations; immediate closure rate 92%; postoperative GI leaks and fistulas — study using clips for upper GI tract leaks had success rate of 89%; type 1 endoscopic retrograde cholangiopancreatography (ERCP)-related perforations — lateral or medial wall duodenal perforation; usually requires surgical intervention, especially if diagnosis delayed; case reports have noted closure with clips or over-the-scope closure devices

Peptic Ulcer Disease and Upper GI Bleeding

Richard J. Saad, MD, Professor of Medicine, University of Michigan Medical School, Ann Arbor

Risks associated with antithrombotic drugs: NSAIDs — study examined relative risk for upper GI complications associated with NSAID and/or aspirin use; examined nonselective NSAIDs and high-dose aspirin (daily dose of 325 mg for 4 wk; study found that use of nonselective NSAIDs increased risk for upper GI complication 2.5-fold when compared to placebo; randomized controlled trial found that use of high-dose aspirin increased risk for upper GI complication 8-fold when compared to placebo; case-control studies found 11-fold increase; complex antithrombotic therapy — studied risk in patients prescribed 1 antithrombotic drug; patient population aged 60 yr or older; aspirin plus anticoagulant drug most common combination therapy used (50% of patients); 6% of patients used aspirin, antiplatelet drug, and anticoagulant drug (triple therapy); triple therapy associated with 52% increase in risk for upper GI bleeding, 600% increase in risk of needing transfusion, and 41% for hospitalization; concluded that complex antithrombotic therapy-related bleeding events clinically significant, particularly in elderly patients

Bleeding and use of left ventricular assist device (LVAD): chart review — 142 patients; identified GI bleeding as decrease in hemoglobin, combined with either occult blood loss or obvious blood in stool; 20% of patients in study experienced GI bleeding, several patients had multiple bleeding events; melena and iron-deficiency anemia, first and second most common presenting symptoms; duodenal ulcer single most common cause of bleeding; conclusions — GI bleeding common in patients with LVAD; measures must be taken to prevent GI bleeding from occurring; peptic ulcer disease (PUD) most common cause of GI bleeding in these patients

Helicobacter pylori and NSAIDs: study — assessed patients hospitalized for upper GI bleeding and matched patients with controls; asked patients about aspirin and NSAID use; found 3-fold increase in risk for upper GI bleeding with H pylori infection, similar increased risk with NSAID use; concomitant NSAID use and H pylori infection found to have synergistic effect in increasing risk of upper GI bleeding (>12-fold increase); aspirin had milder effect on bleeding risk and did not show synergistic effect with H pylori infection; conclusion — H pylori infection, NSAID use, and aspirin all independent risk factors for upper GI bleeding, but H pylori significantly potentiates risk for upper GI bleeding with NSAID use; identification and treatment of H pylori clinically relevant for long-term NSAID users, particularly in populations with high background H pylori infection

Prevention: clopidogrel — oral antiplatelet agent; thienopyridine drug; blocks glycoprotein IIb/IIIa platelet aggregation pathway; indicated for myocardial infarction, ACS, stroke, peripheral artery disease, following stent placement, and in setting of aspirin intolerance; bleeding risk similar to that of aspirin; study found that PPI therapy reduces risk for recurrence of peptic ulcer in patients taking clopidogrel; 2008 consensus statement — recommendations for prevention of aspirin- and NSAID-induced PUD; patients with history of ulcers should be tested for H pylori; PPIs preferred therapy for prophylaxis of aspirin- or NSAID-associated GI injury; 2010 consensus statement — addressed concomitant use of PPI therapy and thienopyridine drugs (specifically clopidogrel); found that clopidogrel and aspirin superior to aspirin alone in reducing coronary stent thrombosis, and in preventing major cardiovascular events in established ischemic heart disease; concomitant clopidogrel and aspirin use results in 2- to 3-fold increase in risk for GI bleeding, compared with aspirin alone; PPIs reduce upper GI bleeding to greater degree than H2 receptor antagonists; probiotics — study found that probiotic therapy reduced gastric mucosal damage and serum proinflammatory cytokines in rats with aspirin-induced injury; another study found dose-dependent reduction in number of gastric ulcers with use of Saccharomyces boulardii probiotic; study found Lactobacillus probiotic beneficial for patients with small-bowel injury from long-term aspirin

Acknowledgements

Drs. Gostout and Jamil spoke at the 13th Annual Educational Meeting in Gastroenterology, held March 1-2, 2013, in Los Angeles, CA, and sponsored by Cedars-Sinai Department of Medicine. Dr. Saad spoke at GI-Liver Wrap-Up, held July 20-22, 2013, in Mackinac Island, MI, and sponsored by the University of Michigan Medical School For future CME activities by these sponsors, visit their web pages: www.csmc.edu/cme for Cedars-Sinai, cme.med.umich.edu/calendar.asp for the University of Michigan. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Suggested Reading

Abraham NS et al: 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 of antiplatelet therapy and NSAID use. Circulation. 2010 Dec 14;122(24):2619-33; Aggarwal A et al: Incidence and management of gastrointestinal bleeding with continuous flow assist devices. Ann Thorac Surg. 2012 May;93(5):1534-40; ASGE Standards of Practice Committee et al: Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc. 2009 Dec;70(6):1060-70; Gomez-Esquivel R and Raju GS: Endoscopic closure of acute esophageal perforations. Curr Gastroenterol Rep. 2013 May;15(5):321; Hallas J et al: Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMJ. 2006;333:726; Iakovou I et al: Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005;293:2126-30; McFarland LV: Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010 May 14;16(18):2202-22; Nguyen NT et al: Management of gastrointestinal leaks after minimally invasive esophagectomy: conventional treatments vs. endoscopic stenting. J Gastrointest Surg. 2011 Nov;15(11):1952-60; Qadeer MA et al: Endoscopic clips for closing esophageal perforations: case report and pooled analysis. Gastrointest Endosc. 2007 Sep;66(3):605-11; Vanbiervliet G et al: The role of clips in preventing migration of fully covered metallic esophageal stents: a pilot comparative study. Surg Endosc. 2012 Jan;26(1):53-9


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