• Nomogram
• Post-endoscopic model
• Pre-endoscopic model
• Prognosis prediction
• Retrospective study
• Upper gastrointestinal bleeding

• gastrointestinal bleeding
• hemodynamic instability
• meta-analysis
• shock

• Ministry of Innovation and Technology of Hungary

• Humans
• Fibrinolytic Agents/adverse effects
• Risk Assessment
• Gastrointestinal Hemorrhage/therapy
• Risk Factors
• Aspirin/adverse effects
• Retrospective Studies

• Gastrointestinal bleeding
• Hemodynamic instability
• Meta-analysis
• Review
• Shock
• Statistics

• Humans
• Gastrointestinal Hemorrhage/diagnosis
• Gastrointestinal Hemorrhage/etiology
• Gastrointestinal Hemorrhage/epidemiology
• Vascular Diseases
• Hemodynamics

• clot formation time
• clotting
• clotting time
• erythrocytes
• microvesicles
• packed red blood cells
• thromboelastometry
• transfusion

• allogeneic blood components
• gastrointestinal bleeding
• transfusion

• Anti-thrombotics
• Guideline
• Non-steroidal anti-inflammatory drug
• Non-variceal upper gastrointestinal bleeding

• aggregation
• hemostasis
• microparticles
• phosphatidylserine
• red blood cell(s)
• shear rate

Anemia is considered a public health issue and is often caused by iron deficiency. Iron-deficiency anemia (IDA) often originates from blood loss from lesions in the gastrointestinal tract in men and postmenopausal women, and its prevalence among patients with gastrointestinal bleeding has been estimated to be 61%. However, few guidelines regarding the appropriate investigation of patients with IDA due to gastrointestinal bleeding have been published.

To review current evidence and guidelines concerning IDA management in gastrointestinal bleeding patients to develop recommendations for its diagnosis and therapy.

Five gastroenterology experts formed the Digestive Bleeding and Anemia Workgroup and conducted a systematic literature search in PubMed and professional association websites. MEDLINE (via PubMed) searches combined medical subject headings (MeSH) terms and the keywords “gastrointestinal bleeding” with “iron-deficiency anemia” and “diagnosis” or “treatment” or “management” or “prognosis” or “prevalence” or “safety” or “iron” or “transfusion” or “quality of life”, or other terms to identify relevant articles reporting the management of IDA in patients over the age of 18 years with gastrointestinal bleeding; retrieved studies were published in English between January 2003 and April 2019. Worldwide professional association websites were searched for clinical practice guidelines. Reference lists from guidelines were reviewed to identify additional relevant articles. The recommendations were developed by consensus during two meetings and were supported by the published literature identified during the systematic search.

From 494 Literature citations found during the initial literature search, 17 original articles, one meta-analysis, and 13 clinical practice guidelines were analyzed. Based on the published evidence and clinical experience, the workgroup developed the following ten recommendations for the management of IDA in patients with gastrointestinal bleeding: (1) Evaluation of hemoglobin and iron status; (2) Laboratory testing; (3) Target treatment population identification; (4) Indications for erythrocyte transfusion; (5) Treatment targets for erythrocyte transfusion; (6) Indications for intravenous iron; (7) Dosages; (8) Monitoring; (9) Indications for intravenous ferric carboxymaltose treatment; and (10) Treatment targets and monitoring of patients. The workgroup also proposed a summary algorithm for the diagnosis and treatment of IDA in patients with acute or chronic gastrointestinal bleeding, which should be implemented during the hospital stay and follow-up visits after patient discharge.

These recommendations may serve as a starting point for clinicians to better diagnose and treat IDA in patients with gastrointestinal bleeding, which ultimately may improve health outcomes in these patients.

• Anemia iron-deficiency
• Erythrocyte transfusion
• Ferric carboxymaltose
• Gastrointestinal hemorrhage
• Iron
• Practice guidelines as topic

• Adult
• Anemia
• Anemia, Iron-Deficiency/diagnosis
• Anemia, Iron-Deficiency/epidemiology
• Anemia, Iron-Deficiency/therapy
• Female
• Gastrointestinal Hemorrhage/diagnosis
• Gastrointestinal Hemorrhage/epidemiology
• Gastrointestinal Hemorrhage/etiology
• Hemoglobins/analysis
• Humans
• Iron
• Male
• Middle Aged

• Blood units
• Comorbidities
• Mortality
• Non-variceal bleeding
• Performance status
• Target
• Threshold
• Transfusion strategy

• Antithrombotics
• Guideline
• Nonsteroidal anti-inflammatory drug
• Nonvariceal upper gastrointestinal bleeding

• Endoscopy, Gastrointestinal
• Gastroenterology
• Gastrointestinal Hemorrhage
• Helicobacter Infections
• Helicobacter pylori
• Humans
• Practice Guidelines as Topic
• Republic of Korea

• Gastrointestinal bleeding
• Non-variceal
• Upper endoscopy

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Anticoagulants/adverse effects
• Cardiovascular Diseases/epidemiology
• Chronic Disease
• Comorbidity
• Diabetes Mellitus/epidemiology
• Endoscopy, Gastrointestinal
• Erythrocyte Transfusion
• Female
• Gastrointestinal Hemorrhage/diagnostic imaging
• Gastrointestinal Hemorrhage/epidemiology
• Gastrointestinal Hemorrhage/therapy
• Hemostasis, Endoscopic
• Humans
• Iran/epidemiology
• Length of Stay
• Liver Diseases/epidemiology
• Lung Diseases/epidemiology
• Male
• Middle Aged
• Prevalence
• Prognosis
• Renal Dialysis/statistics & numerical data
• Risk Factors
• Sex Factors

• endoscopy
• gastrointestinal bleeding

• Anemia
• Evaluation
• Macrocytic
• Management
• Microcytic
• Normocytic
• Red blood cells
• Transfusion
• Transfusion reaction

The benefits of transfusion for acute upper gastrointestinal bleeding (UGIB) have not been well established; however, previous studies suggest that transfusion is associated with adverse outcomes. We performed an observational study using a 10-year database to analyze the association between red blood cell (RBC) transfusion and outcomes in patients with UGIB in the emergency department (ED).

All adult patients with UGIB were identified through diagnostic codes. Hospital mortality was the primary outcome; further bleeding was the secondary outcome. Logistic regression, propensity analyses, and conditional logistic regression were performed to determine factors associated with outcomes. Of 59,188 enrolled patients, 31.6% (n = 18,705) received RBC transfusions within 24 h following presentation to the ED. Hospital mortality was noted in 3.9 and 10.6% of the patients in the non-RBC transfusion and RBC transfusion groups, respectively (P < 0.001). RBC transfusion was associated with increased mortality risk (unadjusted odds ratio (OR) 2.95, 95% confidence interval (CI) 2.75–3.16; P < 0.001) among all patients and in the propensity-matched cohort (unadjusted OR 1.55, 95% CI 1.39–1.72; P < 0.001). Further bleeding was noted in 5.6 and 33.8% of the patients in the non-RBC transfusion and RBC transfusion groups, respectively (P < 0.001). RBC transfusion was associated with increased risk of further bleeding (unadjusted OR 8.60, 95% CI 8.16–9.06; P < 0.001) among all patients and in the propensity-matched cohort (unadjusted OR 2.58, 95% CI 2.37–2.79; P < 0.001).

RBC transfusion was significantly associated with increased rates of hospital mortality and further bleeding in patients with UGIB. Although our findings have strengths, these results are not generalizable to all patients presenting with UGIB, especially patients presenting with exsanguinating bleeding. Additional prospective trials to guide optimal transfusion strategies in UGIB patients are needed.

• Lower gastrointestinal bleeding
• angiography
• colonoscopy
• diverticular bleeding
• endoscopy

• Patient blood management
• gender
• overuse
• transfusion

• Aged
• Aged, 80 and over
• Arthroplasty, Replacement, Hip
• Arthroplasty, Replacement, Knee
• Austria
• Blood Loss, Surgical
• Cohort Studies
• Coronary Artery Bypass
• Elective Surgical Procedures/classification
• Erythrocyte Transfusion/statistics & numerical data
• Female
• Healthcare Disparities/statistics & numerical data
• Hemoglobins/analysis
• Humans
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Postoperative Period
• Risk Factors
• Sex Factors
• Women's Health

• RBC
• blood product
• indications
• product age
• transfusion
• transfusion reaction

• Acute upper gastrointestinal haemorrhage
• blood transfusion
• overtransfusion

• Acute Disease
• Aged
• Aged, 80 and over
• Blood Transfusion
• England/epidemiology
• Female
• Gastrointestinal Hemorrhage/epidemiology
• Gastrointestinal Hemorrhage/therapy
• Hospitals, District/legislation & jurisprudence
• Humans
• Incidence
• Leadership
• Male
• Policy Making
• Retrospective Studies
• State Medicine

• Acute Disease
• Adult
• Aged
• Aged, 80 and over
• Erythrocyte Transfusion/methods
• Feasibility Studies
• Female
• Gastrointestinal Hemorrhage/blood
• Gastrointestinal Hemorrhage/therapy
• Guideline Adherence
• Hemoglobins/metabolism
• Humans
• Male
• Middle Aged
• Patient Selection
• Research Design
• Selection Bias

• MC_U122870183 Medical Research Council

• mortality
• peptic ulcer hemorrhage

• Endoscopic
• Hemostasis
• Peptic Ulcer
• Rebleeding
• Upper Gastrointestinal Bleeding

• Antithrombins/therapeutic use
• Aspirin/adverse effects
• Female
• Gastrointestinal Hemorrhage/drug therapy
• Gastrointestinal Hemorrhage/surgery
• Hemorrhage/drug therapy
• Hemostasis, Endoscopic/methods
• Humans
• Male
• Middle Aged
• Peptic Ulcer/surgery
• Recurrence
• Upper Gastrointestinal Tract/pathology

AIM: To compare the outcome of upper gastrointestinal bleeding (UGIB) between patients receiving restrictive and liberal transfusion.

METHODS: PubMed, EMBASE, and Cochrane Library databases were employed to identify all relevant randomized controlled trials regarding the outcome of UGIB after restrictive or liberal transfusion. Primary outcomes were death and rebleeding. Secondary outcomes were length of hospitalization, amount of blood transfused, and hematocrit and hemoglobin at discharge or after expansion.

RESULTS: Overall, 4 papers were included in this meta-analysis. The incidence of death was significantly lower in patients receiving restrictive transfusion than those receiving liberal transfusion (OR: 0.52, 95%CI: 0.31-0.87, P = 0.01). The incidence of rebleeding was lower in patients receiving restrictive transfusion than those receiving liberal transfusion, but this difference did not reach any statistical significance (OR: 0.26, 95%CI: 0.03-2.10, P = 0.21). Compared with those receiving liberal transfusion, patients receiving restrictive transfusion had a significantly shorter length of hospitalization (standard mean difference: -0.17, 95%CI: -0.30--0.04, P = 0.009) and a significantly smaller amount of blood transfused (standard mean difference: -0.74, 95%CI: -1.15--0.32, P = 0.0005) with a lower hematocrit and hemoglobin level at discharge or after expansion.

CONCLUSION: Restrictive transfusion should be employed in patients with UGIB.

• Upper gastrointestinal bleeding
• Blood transfusion
• Meta-analysis
• Randomized controlled trial

• Biomarkers/blood
• Blood Transfusion/methods
• Blood Transfusion/mortality
• Chi-Square Distribution
• Gastrointestinal Hemorrhage/blood
• Gastrointestinal Hemorrhage/diagnosis
• Gastrointestinal Hemorrhage/mortality
• Gastrointestinal Hemorrhage/therapy
• Hematocrit
• Hemoglobins/metabolism
• Humans
• Length of Stay
• Odds Ratio
• Randomized Controlled Trials as Topic
• Recurrence
• Risk Factors
• Time Factors
• Transfusion Reaction
• Treatment Outcome

• AUC
• GBS
• Glasgow-Blatchford score
• Pre-E RS
• ROC
• area under the curve
• post-E RS
• post-endoscopy Rockall score
• pre-endoscopy Rockall score
• receiver operating characteristic curve

The hemoglobin threshold for transfusion of red blood cells in patients with acute gastrointestinal (GI) bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy.

Objective: The objective was to prove that the restrictive threshold for red blood cell transfusion in patients with acute upper GI bleeding (UGIB) was safer and more effective than a liberal transfusion strategy.

Design: A single-center, randomized controlled trial was conducted.

Setting: Patients with GI bleeding were admitted to the de la Santa Creu i Sant Pau hospital in Barcelona, Spain.

Subjects: The subjects were adult intensive care unit patients admitted with high clinical suspicion of UGIB (hematomemesis, melena, or both). Patients were excluded if they had massive exsanguinating bleeding, acute coronary syndrome, symptomatic peripheral vascular disease, stroke/transient ischemic attack, transfusion within the previous 90 days, recent trauma or surgery, lower GI bleeding, or a clinical Rockall score of 0 with hemoglobin higher than 12 g/dL.

Intervention: A total of 921 patients with severe acute UGIB were enrolled. Of these, 461 were randomly assigned to a restrictive strategy (transfusion when the hemoglobin level fell to below 7 g/dL) and 460 to a liberal strategy (transfusion when the hemoglobin fell to below 9 g/dL). Random assignment was stratified according to the presence or absence of liver cirrhosis.

Outcomes: The primary outcome was rate of death from any cause within the first 45 days. Secondary outcomes were further bleeding, defined as hematemesis or melena with hemodynamic instability or hemoglobin decrease of 2 g/dL or more, and in-hospital complications.

In total, 225 patients assigned to the restrictive strategy (51%) and 65 assigned to the liberal strategy (15%) did not receive transfusions (P <0.001). The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% versus 91%; hazard ratio (HR) for death with restrictive strategy, 0.55; 95% confidence interval (CI) 0.33 to 0.92; P = 0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group and in 16% of the patients in the liberal-strategy group (P = 0.01), and adverse events occurred in 40% and 48%, respectively (P = 0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (HR 0.70, 95% CI 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (HR 0.30, 95% CI 0.11 to 0.85) but not in those with cirrhosis and Child-Pugh class C disease (HR 1.04, 95% CI 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P = 0.03) but not in those assigned to the restrictive strategy.

Compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute UGIB.

Previous research has suggested an association between more liberal red blood cell (RBC) transfusion and greater risk of further bleeding and mortality following acute upper gastrointestinal bleeding (AUGIB).

The Transfusion in Gastrointestinal Bleeding (TRIGGER) trial is a pragmatic cluster-randomised feasibility trial which aims to evaluate the feasibility of implementing a restrictive vs. liberal RBC transfusion policy for adult patients admitted to hospital with AUGIB in the UK. This trial will help to inform the design and methodology of a phase III trial. The protocol for TRIGGER has been published in Transfusion Medicine Reviews. Recruitment began in September 2012 and was completed in March 2013. This update presents the statistical analysis plan, detailing how analysis of the TRIGGER trial will be performed. It is hoped that prospective publication of the full statistical analysis plan will increase transparency and give readers a clear overview of how TRIGGER will be analysed.

ISRCTN85757829

Acute upper gastrointestinal bleeding (AUGIB) is the commonest reason for hospitalization with hemorrhage in the UK and the leading indication for transfusion of red blood cells (RBCs). Observational studies suggest an association between more liberal RBC transfusion and adverse patient outcomes, and a recent randomised trial reported increased further bleeding and mortality with a liberal transfusion policy. TRIGGER (Transfusion in Gastrointestinal Bleeding) is a pragmatic, cluster randomized trial which aims to evaluate the feasibility and safety of implementing a restrictive versus liberal RBC transfusion policy in adult patients admitted with AUGIB. The trial will take place in 6 UK hospitals, and each centre will be randomly allocated to a transfusion policy. Clinicians throughout each hospital will manage all eligible patients according to the transfusion policy for the 6-month trial recruitment period. In the restrictive centers, patients become eligible for RBC transfusion when their hemoglobin is < 8 g/dL. In the liberal centers patients become eligible for transfusion once their hemoglobin is < 10 g/dL. All clinicians will have the discretion to transfuse outside of the policy but will be asked to document the reasons for doing so. Feasibility outcome measures include protocol adherence, recruitment rate, and evidence of selection bias. Clinical outcome measures include further bleeding, mortality, thromboembolic events, and infections. Quality of life will be measured using the EuroQol EQ-5D at day 28, and the costs associated with hospitalization for AUGIB in the UK will be estimated. Consent will be sought from participants or their representatives according to patient capacity for use of routine hospital data and day 28 follow up. The study has ethical approval for conduct in England and Scotland. Results will be analysed according to a pre-defined statistical analysis plan and disseminated in peer reviewed publications to relevant stakeholders. The results of this study will inform the feasibility and design of a phase III randomized trial.

• Erythrocyte Transfusion/adverse effects
• Female
• Gastrointestinal Hemorrhage/etiology
• Humans
• Male

• Erythrocyte Transfusion/adverse effects
• Female
• Gastrointestinal Hemorrhage/etiology
• Humans
• Male

• 2273 Department of Health