Red Cell Transfusion Thresholds Research Articles

Leading digit bias in hemoglobin thresholds for red cell transfusion.

Leading digit bias is a heuristic whereby humans overemphasize the left-most digit when evaluating numbers (e.g., 9.99 vs. 10.00). The bias might affect the interpretation of hemoglobin results and influence red cell transfusion in hospitalized patients. Adults who received a red cell transfusion while registered at the University Health Network (Toronto, Canada) between January 1, 2016 and January 1, 2022 (n = 6 years) were included. The primary analysis excluded apheresis, red cell disorders, radiology suites, and operating rooms. The primary comparison was a regression discontinuity analysis of transfusion occurrence above and below the hemoglobin threshold of 79 g/L (local units). Additional analyses tested other leading digit and control thresholds (71, 81, and 91 g/L). Secondary analyses explored temporal covariates and clinical subgroups. A total of 211,872 red cell transfusions were identified over the study period (median pre-transfusion hemoglobin 76 g/L; interquartile range = 69-92 g/L), with 107,790 inpatient transfusions in the primary analysis. The 79 g/L threshold showed 815 fewer red cell units above the threshold (95% confidence interval [CI]: -1215 to -415). The 69 g/L threshold showed 2813 fewer transfused units (95% CI: -4407 to -1220), and 89 g/L showed 40 fewer units (95% CI: -408 to 328). The effect was accentuated during daytime, weekday, and May-June months, persisted in analyses including all transfusions, and was absent at control thresholds. Leading digit bias might have a modest influence on the decision to transfuse red cells. The findings may inform practice guidelines and quasi-experimental study design in transfusion research.

Perioperative transfusion of red cell products in patients operated at general surgical units of National Hospital of Sri Lanka

Indications for red cell transfusion among general surgical patients have changed over time. Despite a scarcity in evidence, many international guidelines advocate a restrictive transfusion protocol.Objectives: To describe the red cell transfusion practices including transfusion thresholds in general surgical wards of a tertiary hospital in Sri Lanka.Methods: A descriptive cross-sectional study was done in all general surgical units of the National Hospital of Sri Lanka, Colombo. All patients transfused with red cell products for a 3-month period from 1/5/2017-1/8/2017 were included in the study. Indications for transfusion, haemoglobin at transfusion and the number of units transfused was the primary data recorded.Results: A total of 196 patients were included in the study. Most transfusions 79.08% (n=155) were for elective reasons. Most elective transfusions were to facilitate chronic extremity wound healing (52.2%, n=81). Most emergency transfusions were for intraoperative bleeding (31.7%, n=13). The majority (73.5%, n=114) of elective transfusions occurred at a Hb of 7-10 g/dL. The mean number of RBC units transfused in elective circumstances for a Hb of 7-10 g/dL was 1.59. A pre-transfusion blood picture was not available in over 85% (n=132) of elective transfusions. Only a single febrile non-haemolytic transfusion reaction was reported.Conclusions: The study revealed substantial divergence of red cell transfusion thresholds in perioperative practice when compared with international guidelines, nonadherence to rational practice such as obtaining a blood picture prior to elective transfusion and therefore the need to formulate local guidelines. It also highlighted the transfusion burden of diabetic foot disease.

An analysis of quality of life and functional outcomes as reported in randomized trials for red cell transfusions.

Meta-analyses of randomized controlled trials (RCTs) evaluating thresholds for red blood cell (RBC) transfusion typically focus on mortality; however, other outcomes are highly relevant. The aim of this study is to summarize the effects of different transfusion thresholds on the outcomes of quality of life (QoL) and function. We extracted data from RCTs identified in a recently published Cochrane systematic review. Primary analysis was descriptive. A total of 23 RCTs with 13,743 adult participants were included. Fifteen RCTs included patients in the postoperative period, of which 9 RCTs were conducted in hip (n = 3024) and 6 (n = 8672) in cardiac surgeries; 5 RCTs (n = 489) were in patients with hematological malignancies; 2 in the setting of bleeding (gastrointestinal bleed [n = 936] and postpartum [n = 521]); and one RCT (n = 936) included critically ill patients. QoL and function were reported using a variety of questionnaires and tools. The timing of assessments varied between trials. No clear clinical differences in QoL outcomes were identified in comparisons between restrictive and liberal transfusion thresholds. There is no evidence that a liberal transfusion strategy improves QoL and functional outcomes. However, the substantial limitations of many included studies indicate the need for further well-designed and adequately powered trials.

Research on hemoglobin thresholds for red blood cell transfusion in patients with major oncologic surgery is needed!

Research on hemoglobin thresholds for red blood cell transfusion in patients with major oncologic surgery is needed!

Real world reduction in red cell transfusion with restrictive transfusion threshold in haematology inpatients.

The aim of this study was to assess the reduction in red cell transfusions following a change in the red cell transfusion threshold for haematology inpatients from 80 to 70 g/L. Haematology patients are among the high users of red blood cells. We reduced the threshold for transfusion of haematology inpatients to 70 g/L. This was based on evidence provided by randomised controlled trial published in 2020 that showed restrictive transfusion is non-inferior to liberal transfusion. We assessed red cell transfusions for haematology inpatients at Oxford University Hospitals NHS Foundation Trust for 9 months before and 9 months after a change in red cell transfusion threshold from 80 to 70 g/L. After the change in threshold to 70 g/L or less from 80 g/L, the median number of red cell transfusions per month reduced to 88 from 111. This was a 23% reduction in the total number of red cells administered per month. These results show the real-world reductions in transfusion that can be made by putting local transfusion guidelines in line with the international recommendations. This is of particular importance at a time of national blood shortage.

Evaluation of red blood cell transfusion threshold in the management of brain-dead organ donors

The disparity between the demand and supply of organs has necessitated an expansion of the criteria for organ donation. Consequently, numerous guidelines have been proposed for managing brain-dead organ donors (BDODs) to improve their organ function and the organ procurement rate. Therefore, we aimed to evaluate the previously recommended threshold for red blood cell transfusion in BDODs. Medical records of BDODs were retrospectively reviewed from January 2012 to December 2021. We enrolled BDODs who stayed for more than 24 hours at an hospital organ procurement organization. We analyzed their organ function and the rate of organ procurement according to the hemoglobin concentration. A total of 111 BDODs were enrolled and divided into the following 2 groups: hemoglobin (Hb) ≥ 10 g/dL (45.0 %) and Hb < 10 g/dL (55.0 %). There were no significant differences between the groups in the total bilirubin, creatinine, arterial blood lactate, and the rate of organ procurement. A correlation analysis did not reveal any association between the hemoglobin concentration and organ function of the BDODs. Hemoglobin concentration of 10 g/dL cannot be considered a threshold for red blood cell transfusion. Furthermore, organ function is not correlated with a hemoglobin concentration > 7 g/dL. Restrictive transfusion strategy is appropriate for BDOD management.

Rationale and design for the myocardial ischemia and transfusion (MINT) randomized clinical trial

Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (<8g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy. We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin <10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary end point is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary end points include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary end points. The MINT trial will inform RBC transfusion practice in patients with acute MI.

Management of Patients With Acute Lower Gastrointestinal Bleeding: An Updated ACG Guideline.

Acute lower gastrointestinal bleeding (LGIB) is a common reason for hospitalization in the United States and is associated with significant utilization of hospital resources, as well as considerable morbidity and mortality. These revised guidelines implement the Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the use of risk stratification tools, thresholds for red blood cell transfusion, reversal agents for patients on anticoagulants, diagnostic testing including colonoscopy and computed tomography angiography (CTA), endoscopic therapeutic options, and management of antithrombotic medications after hospital discharge. Important changes since the previous iteration of this guideline include recommendations for the use of risk stratification tools to identify patients with LGIB at low risk of a hospital-based intervention, the role for reversal agents in patients with life-threatening LGIB on vitamin K antagonists and direct oral anticoagulants, the increasing role for CTA in patients with severe LGIB, and the management of patients who have a positive CTA. We recommend that most patients requiring inpatient colonoscopy undergo a nonurgent colonoscopy because performing an urgent colonoscopy within 24 hours of presentation has not been shown to improve important clinical outcomes such as rebleeding. Finally, we provide updated recommendations regarding resumption of antiplatelet and anticoagulant medications after cessation of LGIB.

Indications and hemoglobin thresholds for red blood cell transfusion and iron replacement in adults with gastrointestinal bleeding: An algorithm proposed by gastroenterologists and patient blood management experts.

Gastrointestinal (GI) bleeding is associated with considerable morbidity and mortality. Red blood cell (RBC) transfusion has long been the cornerstone of treatment for anemia due to GI bleeding. However, blood is not devoid of potential adverse effects, and it is also a precious resource, with limited supplies in blood banks. Nowadays, all patients should benefit from a patient blood management (PBM) program that aims to minimize blood loss, optimize hematopoiesis (mainly by using iron replacement therapy), maximize tolerance of anemia, and avoid unnecessary transfusions. Integration of PBM into healthcare management reduces patient mortality and morbidity and supports a restrictive RBC transfusion approach by reducing transfusion rates. The European Commission has outlined strategies to support hospitals with the implementation of PBM, but it is vital that these initiatives are translated into clinical practice. To help optimize management of anemia and iron deficiency in adults with acute or chronic GI bleeding, we developed a protocol under the auspices of the Spanish Association of Gastroenterology, in collaboration with healthcare professionals from 16 hospitals across Spain, including expert advice from different specialties involved in PBM strategies, such as internal medicine physicians, intensive care specialists, and hematologists. Recommendations include how to identify patients who have anemia (or iron deficiency) requiring oral/intravenous iron replacement therapy and/or RBC transfusion (using a restrictive approach to transfusion), and transfusing RBC units 1 unit at a time, with assessment of patients after each given unit (i.e., “don’t give two without review”). The advantages and limitations of oral versus intravenous iron and guidance on the safe and effective use of intravenous iron are also described. Implementation of a PBM strategy and clinical decision-making support, including early treatment of anemia with iron supplementation in patients with GI bleeding, may improve patient outcomes and lower hospital costs.

Do liberal thresholds for red cell transfusion result in improved quality of life for patients undergoing intensive chemotherapy for acute myeloid leukemia? A randomized crossover feasibility study.

Not available.

Mortality and morbidity in non-transfusable and transfusable patients: A systematic review and meta-analysis.

Mortality and morbidity in non-transfusable and transfusable patients: A systematic review and meta-analysis.

1339 Haemoglobin Threshold for Red Blood Cell Transfusion in Traumatic Brain Injury. A Systematic Review and Meta-Analysis

Abstract Background Traumatic Brain Injury (TBI) is a significant and growing worldwide healthcare burden. Minimising brain hypoxia is important in preventing secondary brain injury. Anaemia is common in TBI patients but there is little evidence as to which haemoglobin (Hb) threshold transfusion should be considered in TBI patients. Objective This present systematic review and meta-analysis of randomised controlled trials aims to assess the effect of high verses low red blood cell transfusion thresholds on functional outcomes and quality of life in TBI patients. Method We searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, and Web of Science up to June 2020. We also searched clinical trial registers, conference proceedings, and reference lists from previous systematic reviews and included studies. We included randomised studies comparing high verses low Hb threshold for red blood cell transfusion in TBI patients. We assessed the following major outcomes: all-cause mortality, transfusion related adverse events and favourable outcome (Glasgow Outcome Scale, GOS). Results We included 3 RCTs involving 311 participants. Our analysis showed no difference in all-cause mortality (3-6 months) (OR 1.17 (95% CI 0.64 to 2.13)) and no difference in GOS (OR 1.10 (95% CI 0.65 to 1.85)) between transfusing red blood cells at 7g/dL or at 9/10g/dL in moderate to severe TBI. Conclusions There is no difference between a high and a low Hb threshold transfusion policy. However, considering the limitations in current evidence there is a need for future high quality randomised controlled trials.

EBNEO Commentary: Red blood cell transfusion thresholds in extremely low birthweight infants.

Franz AR, Engel C, Bassler D, Rüdiger M, Thome UH, Maier RF, Krägeloh-Mann I, Kron M, Essers J, Bührer C, Rellensmann G, Rossi R, Bittrich HJ, Roll C, Höhn T, Ehrhardt H, Avenarius S, Körner HT, Stein A, Buxmann H, Vochem M, Poets CF; ETTNO Investigators. Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial. JAMA. 2020 Aug 11;324(6):560–570. PMID: 32780138. Erin Grace. Neonatal Fellow. Department of Neonatal Medicine, Women's and Children's Hospital, North Adelaide, South Australia. SAHMRI Women and Kids, South Australian Health and Medical Institute, North Adelaide, South Australia. Robinson Research Institute and the Adelaide Medical School, the University of Adelaide, Adelaide, South Australia. Cathie Hilditch. Paediatric Registrar. SAHMRI Women and Kids, South Australian Health and Medical Institute, North Adelaide, South Australia. Robinson Research Institute and the Adelaide Medical School, the University of Adelaide, Adelaide, South Australia. Amy Keir. Consultant Neonatologist. Department of Neonatal Medicine, Women's and Children's Hospital, North Adelaide, South Australia. Healthy Mothers, Babies and Children Theme, South Australian Health and Medical Institute, North Adelaide, South Australia. Robinson Research Institute and the Adelaide Medical School, the University of Adelaide, Adelaide, South Australia. In this European multicentre randomised controlled trial, the Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low birth Weight Infants (ETTNO), 1013 preterm infants with a birthweight less than 1000 grams were included. The study was undertaken across 2011–2014 with longer term follow-up beyond this period.1 At 24 months’ corrected age, rates of the primary outcome of death or neurodevelopmental impairment were similar in the liberal and restrictive threshold groups (44.4% and 42.9%; odds ratio, 1.05). The rates of mortality, cognitive impairment and complications including bronchopulmonary dysplasia and necrotising enterocolitis were similar between groups. To examine the study more closely, randomisation occurred with the first 72 hours of age with the majority of infants randomised at 2.5 days of age. Twenty-five per cent of infants in each group received at least one red blood cell transfusion prior to randomisation. Deferred/delayed cord clamping (DCC) for 30–45 seconds was implemented at each study site with 308/492 (63%) in the liberal group and 319/519 (61%) in the restrictive group receiving DCC. The mean difference in mean haematocrits ranged from 1.5 to 3.4% from the week of randomisation to week 11. Whether this difference is clinically meaningful is worth considering. The authors note that the separation in these haematocrit values, and consequently the potential oxygen-carrying capacity achieved, may be too small to cause a difference in study outcomes.1 The lowest mean haematocrit in the restrictive group was in week 9 at 31.7% (SD 4.6). A comprehensive list of further study limitations is well laid out by the authors. These included potential limited generalisability due to the infants being primarily from a white German population group, the changes in clinical practices that may have occurred since 2011–2014, and the proportion of infants who received a red blood cell transfusion not justified by the study protocol. Risk of bias (ROB) in the study, assessed using the Cochrane ROB tool,2 was deemed low risk overall. The potential for post randomisation confounding exists, with 14% of infants receiving a transfusion not justified by the protocol and 7% did not receive a transfusion when dictated by the protocol. Analysis of the per-protocol population was consistent with the primary analysis findings. Other postrandomisation confounding risks were deemed low as there was minimal loss to follow up with similar numbers between groups. The results of the recently published Transfusion of Prematures (TOP) trial are consistent with this trial. Combining the results will hopefully enable a much anticipated individual patient data meta-analysis.1 Anaemia of prematurity is a term used broadly across the highly variable and complex course of prematurity in relation to red blood cell transfusion practice. It is possible that a difference approach to transfusion in the first days of age requires a transfusion trigger based on optimisation of oxygen kinetics, rather than a threshold per se.4 At this point, however, lower red cell transfusion thresholds compared to more liberal thresholds seem an appropriate clinical approach, especially for those preterm infants 48–72 hours of age or older. https://ebneo.org/transfusion-thresholds-low-birthweight-infants The authors have no conflicts of interest to declare.

RBC-Enhance: A Randomized Pilot Feasibility Trial of Red Cell Transfusion Thresholds in Myelodysplastic Syndromes

RBC-Enhance: A Randomized Pilot Feasibility Trial of Red Cell Transfusion Thresholds in Myelodysplastic Syndromes

Recent advances in the management of acute upper gastrointestinal bleeding

Upper gastrointestinal bleeding is a common medical emergency with associated significant morbidity and mortality. There are multiple published national and international guidelines on the management of acute upper gastrointestinal bleeding (AUGIB). However, the 2015 National Confidential Enquiry into Patient Outcome and Death group (NCEPOD) report identified several areas of concern regarding suboptimal care. This article discusses the latest evidence and guidance on the pre-endoscopic, endoscopic and post-endoscopic management of patients presenting with AUGIB. AUGIB should be assessed for risk stratification using a validated score, such as the Glasgow-Blatchford Score, Rockall Score or AIMS65. Treatment considerations include the optimum threshold for red blood cell transfusion, as well as the reintroduction of antithrombotic agents. Novel endoscopic therapies include haemostatic powder spray, over-the-scope clips, ultrasound doppler probes and self-expandable oesophageal stents.

Systematic reviews and meta-analyses comparing mortality in restrictive and liberal haemoglobin thresholds for red cell transfusion: an overview of systematic reviews

BackgroundThere are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality.MethodsThis was a systematic review of systematic reviews (overview). We searched MEDLINE, Embase, Web of Science Core Collection, PubMed, Google Scholar, and the Joanna Briggs Institute EBP Database, from 2008 to 2018. We included systematic reviews and meta-analyses of randomised controlled trials comparing mortality in patients assigned to red cell transfusion strategies based on haemoglobin thresholds. Two independent reviewers extracted data and assessed methodological quality. We assessed the methodological quality of included reviews using AMSTAR 2 and the quality of evidence pooled using an algorithm to assign GRADE levels.ResultsWe included 19 systematic reviews reporting 33 meta-analyses of mortality outcomes from 53 unique randomised controlled trials. Of the 33 meta-analyses, one was graded as high quality, 15 were moderate, and 17 were low. Of the meta-analyses presenting high- to moderate-quality evidence, 12 (75.0%) reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and four (25.0%) reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. We found few systematic reviews addressed clinical differences between included studies: variation was observed in haemoglobin threshold concentrations, the absolute between group difference in haemoglobin threshold concentration, time to randomisation (resulting in transfusions administered prior to randomisation), and transfusion dosing regimens.ConclusionsMeta-analyses graded as high to moderate quality indicate that in most patient populations no difference in mortality exists between patients assigned to a restrictive or liberal transfusion strategy.Trial registrationPROSPERO CRD42019120503

In search for a haemoglobin threshold in myelodysplastic syndromes.

In search for a haemoglobin threshold in myelodysplastic syndromes.

Current red cell transfusion practice: are we too liberal with this precious resource?

Current National Institute for Health and Care Excellence (NICE) guidance recommends restrictive thresholds for red cell transfusion, dependent upon patient factors such as haemodynamic status.1 NICE also recommends that individuals should be provided with information regarding the risks and benefits of blood transfusion and those patients should give informed consent prior to blood transfusion. Informed consent is a recurrent theme in the Infected Blood Inquiry.2 We audited red cell transfusion (RCTx) practices according to NICE guidelines and examined documentation around consent. The study consisted of 4 parts.

Red cell transfusion in outpatients with myelodysplastic syndromes: a feasibility and exploratory randomised trial.

Optimal red cell transfusion support in myelodysplastic syndromes (MDS) has not been tested and established. The aim of this study was to demonstrate feasibility of recruitment and follow-up in an outpatient setting with an exploratory assessment of quality of life (QoL) outcomes (EORTC QLQ-C30 and EQ-5D-5L). We randomised MDS patients to standardised transfusion algorithms comparing current restrictive transfusion thresholds (80g/l, to maintain haemoglobin 85-100g/l) with liberal thresholds (105g/l, maintaining 110-125g/l). The primary outcomes were measures of compliance to transfusion thresholds. Altogether 38 patients were randomised (n=20 restrictive; n=18 liberal) from 12 participating sites in UK, Australia and New Zealand. The compliance proportion for the intention-to-treat population was 86% (95% confidence interval 75-94%) and 99% (95-100%) for restrictive and liberal arms respectively. Mean pre-transfusion haemoglobin concentrations for restrictive and liberal arms were 80g/l (SD6) and 97g/l (SD7). The total number of red cell units transfused on study was 82 in the restrictive and 192 in the liberal arm. In an exploratory analysis, the five main QoL domains were improved for participants in the liberal compared to restrictive arm. Our findings support the feasibility and need for a definitive trial to evaluate the effect of different red cell transfusion thresholds on patient-centred outcomes.

Systematic reviews and meta-analyses comparing mortality in restrictive and liberal haemoglobin thresholds for red cell transfusion: protocol for an overview of systematic reviews

IntroductionThere has been a significant increase in the number of systematic reviews and meta-analyses of randomised controlled trials investigating thresholds for red blood cell transfusion. To systematically collate, appraise and...