the acute management of nonvariceal upper gastrointestinal bleeding - hindawi 2012

Hindawi Publishing CorporationUlcersVolume 2012, Article ID 361425, 8 pagesdoi:10.1155/2012/361425

Review Article

The Acute Management of Nonvariceal UpperGastrointestinal Bleeding

Hisham AL Dhahab and Alan Barkun

Department of Gastroenterology, McGill University Health Center, 1650 Cedar Avenue, Montreal, QC, Canada H3G 1A4

Correspondence should be addressed to Alan Barkun, [email protected]

Received 10 August 2012; Accepted 3 October 2012

Academic Editor: T. Arakawa

Copyright © 2012 H. AL Dhahab and A. Barkun. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Background. The mortality from nonvariceal upper gastrointestinal bleeding is still around 5%, despite the increased use of proton-pump inhibitors and the advancement of endoscopic therapeutic modalities. Aim. To review the state-of-the-art managementof acute non variceal upper gastrointestinal bleeding from the presentation to the emergency department, risk stratification,endoscopic hemostasis, and postendoscopic consolidation management to reduce the risk of recurrent bleeding from peptic ulcers.Methods. A PubMed search was performed using the following key words acute management, non variceal upper gastrointestinalbleeding, and bleeding peptic ulcers. Results. Risk stratifying patients with acute non variceal upper gastrointestinal bleedingallows the categorization into low risk versus high risk of rebleeding, subsequently safely discharging low risk patients earlyfrom the emergency department, while achieving adequate hemostasis in high-risk lesions followed by continuous proton-pumpinhibitors for 72 hours. Dual endoscopic therapy still remains the recommended choice in controlling bleeding from peptic ulcersdespite the emergence of new endoscopic modalities such as the hemostatic powder. Conclusion. The management of nonvaricealupper gastrointestinal bleeding involves adequate resuscitation, preendoscopic risk assessment, endoscopic hemostasis, and postendoscopic pharmacological and nonpharmacological treatment.

1. Introduction

About 10% of the population in the Western world willexperience peptic ulcer disease at some point during theirlives. Individuals with peptic ulcer disease may presentwith a variety of gastrointestinal (GI) symptoms includingabdominal pain, vomiting, and bleeding. Indeed, peptic ulcerdisease is the most common cause of conditions such asupper GI hemorrhage and perforation, which are associatedwith high mortality and morbidity [1].

Acute upper gastrointestinal bleeding (AUGIB) is oneof the commonest causes for hospitalization worldwide. Inthe United States, there are 250,000 to 300,000 hospitaladmissions and 15,000 to 30,000 deaths each year resultingfrom acute upper GI hemorrhage [2]. The mortality frombleeding peptic ulcer disease remains unchanged around 5%[3, 4], despite the use of PPI and advances in endoscopictherapy. The unchanged mortality rate might reflect the

increased use of aspirin and NSAID in the elderly populationwith multiple underlying comorbidities that puts suchpatients at higher risk of both bleeding and death [5]. Theincidence of AUGIB ranges from 48 to 160 cases per100 000 adults per year [6]. For patients with and withoutcomplications of nonvariceal upper gastrointestinal bleeding(NVUGIB) in the United States, mean lengths of stay were 4.4and 2.7 days and hospitalization costs were $5632 and $3402(2004 US dollars), respectively [6].

Our paper will focus on the state-of-the-art managementof bleeding peptic ulcer disease. There are five cornerstoneelements critical to the appropriate management of patientswith NVUGIB. They are resuscitation, risk assessment,preendoscopic care, endoscopic management, and posten-doscopic care including pharmacological and nonpharmaco-logical therapies. The issue of secondary prophylaxis will notbe addressed in this particular paper, but readers are referredto a recent narrative review on the topic [7].

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2. Resuscitation and Initial Assessment

Patients presenting with upper gastrointestinal bleeding areat risk of hemodynamic shock and airway compromisetherefore, the first priority is to assess the adequacy of theairway, as well as the patient’s breathing and circulation.Venous access should be achieved with at least 2 large-bore cannulae, and patients with active bleeding should bemonitored in a high-dependency unit with pulse oximetry,cardiac monitoring, automated blood pressure readings,close monitoring of urine output, and, ideally, central venouspressure monitoring. As a minimum, all patients should beblood typed and cross-matched for an appropriate numberof units of packed red blood cells with blood sent forhemoglobin, hematocrit, platelets, coagulation time, andelectrolytes [8]. Hemodynamic shock is associated with anincreased mortality [9, 10]. There are no studies comparinginitial resuscitation with crystalloid or colloid in patientswith gastrointestinal bleeding.

Acute upper gastrointestinal bleeding (AUGIB) is a verycommon indication for transfusion of blood components. Astudy from the United Kingdom found that this indicationalone accounts for 14% of the national red cell supply [11].There is a widespread variation in clinical practice that influ-ences transfusion threshold, due to several factors includingphysician, patient factors, and hospital local guidelines. Thevalue of RBC transfusion in exsanguinating NVUGIB isself-evident, and the small proportion of patients requiringmassive transfusion should be managed in accordance withlocal major hemorrhage protocols in close liaison withhospital transfusion teams. Red blood cell transfusion israrely indicated when hemoglobin (Hg) levels are greaterthan 100 g/L and is almost always indicated when the levelsfall below 60 g/L. The risks associated with the consequencesof acute anemia should be weighed against the risks oftransfusion. Patients requiring massive transfusion are likelyto develop a dilutional coagulopathy and will require trans-fusion of platelets and fresh frozen plasma, again guided bylocal hospital protocols. However, in less severe bleeding,the benefit of RBC transfusion is unclear. A retrospectiveobservational study of 4441 patients admitted with AUGIB inthe United Kingdom found that for patients presenting witha Hg of > 80 g/L, transfusion within 12 hours was associatedwith a two-fold increase in the subsequent risk of rebleeding(odds ratio (OR) 2.26, 95% confidence interval (CI) 1.76–2.90), although confounding by indication could not beexcluded [12]. A systematic review of 10 RCTs comparingrestrictive versus liberal RBC transfusion strategies in 1780patients from a variety of clinical settings concluded that arestrictive approach led to a 42% reduction in the probabilityof receiving transfusions with no effect on mortality, ratesof cardiac events, morbidity, or length of hospital stay [13].Therefore, in patients presenting with AUGIB who are notmassively bleeding, transfusion can probably be withheld inthe presence of Hg levels as low as 70 to 80 g/L, providedthere is no evidence of comorbid cardiovascular disease.International guidelines recommend initiating red blood celltransfusions for most critically ill patients when Hg levelsdecrease to less than 70 g/L, with a target level from 70

to 90 g/L, in the absence of tissue hypoperfusion, coronaryartery disease, or acute hemorrhage [14].

The prognostic value of the international normalizedratio (INR) following presentation with NVUGIB is poorlycharacterized. In the Canadian Registry on NonvaricealUpper Gastrointestinal Bleeding and Endoscopy (RUGBE)cohort of 1869 patients with NVUGIB, a presenting INRof greater than 1.5 was associated with almost a two-foldincreased risk of mortality (OR 1.95, 95% CI 1.13–3.41)after adjustment for confounders, but not an increased riskof rebleeding [15]. Another study in patients with uppergastrointestinal bleeding (UGIB), using a historical cohortcomparison, suggested that correcting an INR to less than1.8 as part of intensive resuscitation led to lower mortalityand fewer myocardial infarctions in the intervention group[16]. The completeness of correction of a coagulopathy mustbe considered, but should not delay the performance ofearly endoscopy (defined as within 24 hours of presentation)[6]. This recent consensus recommendation is based onrecognition of the benefits of early endoscopic interventioncoupled to the decreased tissue damage associated withnewer ligation hemostatic techniques such as endoscopicclips or hemostatic powders. Moreover, limited observationaldata also suggest that endoscopic hemostasis can be safelyperformed in patients with an elevated INR as long as it isnot supratherapeutic (in this study a value of 2.5) [17]. Theuse of Prothrombin Complex Concentrate (PCC) should beconsidered in the reversal of Warfarin in patients presentingwith life threatening hemorrhage, including gastrointestinalhemorrhage. PCC appeared to be a more cost-effectivetreatment than FFP for the emergency reversal of Warfarin,from the perspective of the UK NHS, in a systemic literatureanalysis involving 1085 patients in 16 studies [18]. Themanagement of newer anticoagulants that cannot be reversedrepresents an emerging issue [19].

The role of the nasogastric tube (NGT) in the initialassessment of patients presenting with NVUGIB remainscontroversial. It carries a prognostic value in identifyinghigh-risk lesions [20], facilitates gastric lavage prior toperforming endoscopy which has been shown to improvefundic visualization acutely, but may compromise the airway.The NGT can be negative in up to 15% of upper gastroin-testinal bleeding cases, especially when it is from a duodenalsource [21]. The presence of fresh red blood in the NGTaspirate has been found to be an independent predictorof adverse outcome on multivariable analysis [22], and isalso a predictor of high-risk lesions in patients who arehemodynamically stable without evidence of hematemesis.Indeed a bloody nasogastric aspirate exhibits a specificityfor high-risk endoscopic lesions (75.8% : 95% CI 70.0–80.0)with a negative predictive value of 77.9% (95% CI 73.2–82.0)[20].

3. Risk Stratification Scoring Systems

The clinical predictors of increased risk for rebleedingor mortality include age greater than 65 years, shock,poor overall health status, comorbid illnesses, low initialhemoglobin levels, melena, transfusion requirement, fresh

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20

15

10

5

0

Ou

tcom

e

Rockall score

Mortality (%)Rebleeding (%)

0 1 2 3 4 5 6 7 ≥8

Figure 1: Mortality and bleeding rates according to the completeRockall score.

red blood on rectal examination, in the emesis, or in thenasogastric aspirate, sepsis, and elevated urea, creatinine, orserum aminotransferase levels [23]. Other factors predictiveof outcomes include chronic alcoholism, active cancer, orunsuitable sociofamily conditions [24], as well as an AcutePhysiology and Chronic Health Evaluation (APACHE) IIscore of 11 or greater [25]. There exists well validatedprognostic scoring systems for patients presenting withAUGIB, these scores help to categorize patients into low-riskversus high-risk patients and predict the risk of rebleeding,mortality rates as well as those requiring endoscopic inter-vention.

The most extensively validated scores are the Rockall(Table 1 and Figure 1) [26] and Blatchford scores (Table 2)[27]. The preendoscopic or clinical Rockall and Blatchfordscores use only clinical and laboratory data, whereas thecomplete Rockall score in addition takes into considerationand uses endoscopic data to predict subsequent rebleedingor mortality.

The complete Rockall score has been said to be supe-rior to both the preendoscopy clinical Rockall scores andBlatchford score in predicting mortality and rebleeding [28],although these findings have been questioned more recently[29].

The Blatchford score is more useful than the clinicalRockall score in identifying low-risk patients who do notrequire therapeutic endoscopy, and specifically those patientswith a score of zero may be safely triaged from the ED tooutpatient management [30, 31].

Endoscopically, the following features predict theincreased risk of rebleeding: active bleeding at the time ofendoscopy, large ulcer size >2 cm, bleeding ulcers located on

the lesser curvature or posterior duodenal wall, and high-risk stigmata classified according to the Forrest classification(Table 3) [32].

4. Preendoscopic Medical Therapy

4.1. Proton-Pump Inhibitors. Proton-pump inhibitors (PPIs)play an important role in the stabilization of clot formationin response to bleeding peptic ulcers through pH-dependentfactors, by raising the pH to 6, helping in optimizing plateletaggregation [33]. Raising the pH may also decrease pepsinmediated clot lysis and fibrinolytic activity. A Cochranesystematic review and meta-analysis of 6 RCTs including2223 patients comparing PPI with control administrations(placebo or histamine-2-(H2)receptor antagonists) found noevidence that preendoscopic administration of PPIs led to areduction in the most important clinical outcomes followingAUGIB, namely, rebleeding, mortality, or need for surgery[34]. However, the use of preendoscopic PPI may delay theneed for endoscopic intervention by down staging high-riskendoscopic lesions into low risk, that is, downstaging theForrest classification (Table 3). This may prove beneficialwhen early endoscopy is not feasible or local expertise islimited, the use of preendoscopic PPI however should replaceappropriate initial resuscitation or delay the performance ofearly endoscopy [35].

Cost-effective scenarios optimizing the possible role ofthis preemptive pharmacotherapy have been identified andinclude a high likelihood of bleeding from a nonvaricealsource and delayed access to endoscopy [36].

4.2. Octreotide and Somatostatin Analogues. Current inter-national recommendations state that somatostatin oroctreotide are not recommended in the routine managementof patients with acute NVUGIB [23]. RCT have shownthat in patients with a bleeding ulcer following successfulendoscopic hemostasis, pantoprazole continuous infusionwas superior to somatostatin to prevent bleeding recurrenceand promote the disappearance of the endoscopic stigmata.Nevertheless, no differences were seen in the need for surgeryor mortality [37]. Such an approach should of coursebe considered if a variceal cause of bleeding is suspected[38], or if patients are exsanguinating from any uppergastrointestinal tract etiology.

4.3. Prokinetic Agents. The use of prokinetic agents prior toendoscopy may improve diagnostic yield in selected patients;however, they are not warranted for routine use in all patientswho present with UGIB. A meta-analysis [39] of 3 trials thatevaluated erythromycin [40–42], comprising 316 patients,and 2 abstracts that evaluated metoclopramide [43] foundthat the use of a prokinetic agent significantly reduced theneed for repeated endoscopy (odds ratio (OR), 0.51 (95% CI,0.30 to 0.88)) [39].

5. Endoscopic Therapy

5.1. Timing of Endoscopy. Early endoscopy (within 24hours of presentation) is recommended for most patients

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Table 1: Points scheme allocation for the complete Rockall score.

Score 0 1 2 3

Age <60 60–79 ≥80

Vital signs No shock Tachycardia HR > 100 Hypotension SBP < 100

Comorbidities noneCardiac failure/ischemicdisease/other conditions

Liver, renal failure, andadvanced malignancy

DiagnosisMallory Weiss tear, no

bleeding or lesionsidentified

Other diagnosis Malignancy of upper GI tract

Stigmata of bleeding None or dark spot onlyBlood in GI tract, active bleedingor visible vessel, or adherent clot

Rockall score [8].

Table 2: Points scheme allocation for the Blatchford score.

Parameter Points

Urea mmol/L

6.5–7.9 2

8–9.9 3

10–25 4

>25 6

Haemoglobin g/L (for men)

120–129 1

110–119 3

<110 6

Haemoglobin g/L (for women)

100–119 1

<110 6

SBP mm Hg

100–109 1

90–99 2

<90 3

Others

Pulse > 100 1

Melena on presentation 1

Syncope on presentation 2

Hepatic disease 2

Cardiac failure 2

Blatchford score [8].

Table 3: The Forrest classification.

Forrest class Endoscopic appearance

High risk

1a Active spurting bleeding

1b Active oozing bleeding

2a Non Bleeding visible vessel

2b Adherent clot

Low risk

2c Pigmented clot

3 Clean base ulcer

with acute upper gastrointestinal bleeding. Early endoscopy(within the first 24 hours), using risk classification based

on clinical and endoscopic criteria, has been shown topermit the safe and prompt discharge of patients classifiedas low risk. Furthermore, it also improves patient outcomesfor patients classified as high-risk, while reducing use ofresources for patients classified as either low or high-risk [6].Indeed the performance of early endoscopy decreases lengthof hospital stay in patients at low risk [44], high-risk [45],and combined patient groups [46]. No additional benefit hasbeen shown when using a practice of very early endoscopyat 2 or 12 hours. A systemic review of 3 trials [45, 47],comprising 528 patients, found no significant reduction inrebleeding (OR, 0.71 (CI, 0.28 to 1.81)), surgery (OR, 1.16(CI, 0.39 to 3.51)), or mortality (OR, 0.70 (CI, 0.14 to 3.57))with urgent (1 to 12 hours) endoscopy. Recent observationaldata, however, suggest that earlier endoscopy (at 13 hours)may be beneficial to very ill patients (Blatchford > 12) [48].

5.2. Endoscopic Therapeutic Modalities. There exist manyendoscopic modalities for treating bleeding peptic ulcerdisease. These include mechanical devices such as endoscopicclips and thermal probes, and it is needless to say that it caninject epinephrine, saline, sclerosing agents, thrombin, andfibrin glue. More recently, hemostatic powders have also beenintroduced [49].

Endoscopic therapy is warranted for high-risk lesionsthat is, Forrest classification 1a, 1b, 2a, and 2b, 2b becauseof their greatest propensities for rebleeding if left untreated.Meta-analyses have confirmed that endoscopic hemostasis inthis group of patients results in significant improvementsin rebleeding, but have been underpowered to show anybetter improvement in the need for surgery or mortality[32, 36, 38, 50]. Although all endoscopic techniques providebenefit, injection of epinephrine alone is superior to medicalmanagement alone, but is inferior to all other methods andshould no longer be used as a sole endoscopic treatmentwhen other methods are available. Clinicians should thusfavor a sole thermal method, the combination of injectionfollowed by thermal or positioning of a clip, or the injectionof a clip followed by injection (studied in this sequence inmost trials). Compared with epinephrine, further bleedingwas reduced significantly by other monotherapies (relativerisk (RR), 0.58 (95% CI, 0.36–0.93) [36]; number-needed-to-treat (NNT), 9 (95% CI, 5–53)), and epinephrine followedby another modality (RR, 0.34 (95% CI, 0.23–0.50); NNT, 5

Ulcers 5

(95% CI, 5–7)). Compared with no endoscopic therapy, fur-ther bleeding was reduced by thermal contact (heater probe,bipolar electrocoagulation) (RR, 0.44 (95% CI, 0.36–0.54);NNT, 4 (95% CI, 3–5)) and sclerosant therapy (RR, 0.56(95% CI, 0.38–0.83); NNT, 5 (95% CI, 4–13)). Clips weremore effective than epinephrine (RR, 0.22 (95% CI, 0.09–0.55); NNT, 5 (95% CI, 4–9)), but not different than othertherapies, although the latter studies were heterogeneous,showing better and worse results for clips [36, 51].

A special consideration is that of patients with adherentclots. Indeed the role of endoscopic therapy for ulcers withadherent clots is controversial. Recommendations state thatendoscopic therapy may be considered, although intensivePPI therapy alone may be sufficient. Endoscopic therapy foradherent clots refers to preinjecting them with epinephrinebefore shaving them down with a snare technique—withoutdisrupting the pedicle of the clot—and then applying, com-bination treatment to the residual stigmata of hemorrhage ifa high-risk lesion remains; indeed, the endoscopic findingspresent after clot removal should be appropriately managed[52, 53]. The risk for rebleeding with clots that remainadherent after washing without endoscopic therapy (with orwithout PPI therapy) has been reported to be as low as 0%to 8% [54] but also as high as 25% to 35% [52, 55, 56]in clinically high-risk patients. One meta-analysis of 5 RCTs[51], comprising 189 patients with adherent clots, foundno significant benefits for endoscopic versus no endoscopictherapy (relative risk (RR), 0.31 (CI, 0.06 to 1.77)).

The use of hemostatic powders is an emerging endo-scopic hemostatic technology, part of a family of productsthat was recently introduced in the management of upperGI bleeding [49]. It is composed of a proprietary inorganicpowder that, when put in contact with moisture in theGI tract, becomes coherent and adhesive, thus serving as amechanical barrier for hemostasis. A prospective, pilot studyinvolving 20 patients with nonmalignant upper GI bleedingshowed that the application of TC-325 was associated witha 95% initial hemostasis with no active bleeding seen onrepeat EGD at 72 hours, followed by total elimination of theinorganic substance without complications such as intestinalobstruction or embolization [57].

The role of second-look endoscopy, a preplanned repeatendoscopy performed 16–24 hours after an initial endoscopictreatment, has been a source of controversy. A recent meta-analysis suggests that in the absence of high-dose PPI,especially in PUB patients at very high-risk of rebleeding,routine second-look endoscopy appears effective. However,the generalizability of these results to the era of high-dose PPIand otherwise unselected patients with high-risk stigmata isunclear [33]. This is why current recommendations suggestthis approach be adopted only in patients at a particularlyhigh-risk of rebleeding following initial endoscopic hemosta-sis [6].

6. Postendoscopic Management

6.1. Proton-Pump Inhibitors. It has been well documentedthat high-risk lesions require 72 hours following endoscopictherapy to evolve from a high-risk to a low-risk stigmata,

justifying the 3-day duration of the profound acid suppres-sion [58].

High-dose intravenous PPI therapy (e.g., a PPI at a doseof 80 mg bolus dose followed by 8 mg/h infusion over 72hours) should be administered to patients with high-riskstigmata who have received successful endoscopic therapy.This recommendation is based on a meta-analysis of RCTsincluding 5792 patients in which PPI therapy reduced theincidence of rebleeding (OR 0.45, 95% CI 0.36–0.57) andneeded for surgery (OR 0.56, 95% CI 0.45–0.70), but notmortality (OR 0.90, 95% CI 0.67–1.19) [59, 60].

Furthermore, PPIs improve mortality in patients withHRS, but only if they have initially undergone endoscopichemostasis (i.e., mainly high dose IV) [6]. These findingshave also been confirmed in a “real-life” setting. The optimaldose and route of administration of PPIs, however, remainscontroversial but the highest quality data apply to the high-dose regimen, thought to be a class effect, as describedabove [6]. The optimal dose and route of administration,however, remain unclear. The data suggesting lower-dose PPImay be efficacious have been hampered by methodologicallimitations [61]. All patients should be discharged on a singledaily oral dose of a PPI; the duration of PPI is determined bythe underlying etiology of the bleeding ulcer, with perhapsa consideration for double-dosing if patients have bled fromesophagitis [6].

6.2. Testing for Helicobacter Pylori. All patients with bleed-ing peptic ulcers should be tested for Helicobacter pylori(depending on the local prevalence) and receive eradicationtherapy if it is positive. A meta-analysis demonstrated thateradication of H. pylori was significantly more effective thanPPI therapy alone in preventing rebleeding from pepticulcer disease. If Helicobacter pylori is not detected in theacute setting, then repeat testing is indicated. Indeed asystematic review of 23 studies found that diagnostic tests forHelicobacter pylori infection (including serology, histology,urea breath test, rapid urease test, stool antigen, and culture)demonstrate high positive predictive value (0.85 to 0.99)but low negative predictive value (0.45 to 0.75) in thesetting of AUGIB, with 25% to 55% of Helicobacter-pylori-infected patients yielding false-negative results in the acutecontext of upper gastrointestinal bleeding [6] (Figure 2).The full reasons for the observed high false negative rate ofHelicobacter pylori testing in the acute setting of bleeding areunclear, but in part relate to the alkalotic milieu imparted bythe presence of blood in the gastric lumen and the resultantproximal migration of the bacterium in such a setting [62].

6.3. Aspirin in AUGIB. A recent RCT out of Hong Konghas shown that it is more deleterious to withhold ASAamongst patients using it for secondary cardiovascularprophylaxis than to restart it early on. Based on thesedata, consensus recommendations state that in patients whoreceive low-dose ASA and develop acute ulcer bleeding,ASA therapy should be restarted as soon as the risk forcardiovascular complication is thought to outweigh the riskfor bleeding [63]. ASA is today usually restarted within 3–5days of the presentation with bleeding, after appropriate

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0

10

20

30

40

50

60

70

80

90

100

Serology Rapid urease

Histology Culture Urea breath

Stool antigen

+ve predictive value −ve predictive value

Figure 2: Diagnostic test performance for H. pylori detection inthe acute setting of an episode of nonvariceal upper gastrointestinalbleeding.

discussions amongst the multidisciplinary treating team thatcan includes general practitioners, internists, cardiologists,neurologists, gastroenterologists, and intensivists.

7. Summary

Adequate resuscitation and initial risk assessment are crucialin patients presenting with AUGIB. Early endoscopy allowsfor categorization of patients into low versus high-risk ofrebleeding and delivery of endoscopic hemostasis. Prokinet-ics are helpful in visualizing bleeding lesions at the initialendoscopy. Dual endoscopic modality therapy is superiorto epinephrine injection alone followed by continuous PPIinfusion for 72 hours should be applied for high-riskstigmata of rebleeding.

All patients should be discharged on a single daily oraldose of a PPI the duration of PPI is determined by theunderlying etiology of the bleeding ulcer, while in patientswho are on antiplatelet agents, the cardiothrombotic risksshould be balanced against the risk of further bleeding orrebleeding. ASA should be soon restarted in patients withhigh-risk of cardiothrombotic events. Finally, all patientspresenting with bleeding ulcers should be tested for H. pylori,understanding that there is a high false negative rate in theacute setting of UGIB.

Abbreviations

GI: GastrointestinalAUGIB: Acute upper gastroIntestinal bleedingNVUGIB: Nonvariceal upper gastroIntestinal bleedingPPI: Proton-pump inhibitorsPCC: Prothrombin complex concentrateNGT: Nasogastric tube

NSAID: Nonsteriodal anti-inflammatory drugsASA: AspirinCOX-2: Cyclo-oxygenase 2PUB: Peptic ulcer bleedingHRS: High-risk stigmataHg: HemoglobinRCT: Randomized control trials.

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