The Cochrane database of systematic reviewsOct 20, 2025

Guiding red blood cell transfusions using transfusion limits and other methods

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

A restrictive transfusion strategy reduced the risk of receiving at least one red blood cell transfusion by 42% across various clinical contexts.

Restrictive transfusion strategies did not change the risk of 30-day mortality compared to liberal strategies.
In patients with gastrointestinal bleeding, a restrictive strategy was associated with a lower 30-day mortality.
Critically ill patients with brain injury showed better neurological outcomes with a liberal transfusion strategy at 6 to 12 months.
Transfusion-specific reactions occurred more frequently with the liberal strategy.
There was no clear difference in 30-day mortality among pediatric patients between restrictive and liberal transfusion strategies.

Simplified

BACKGROUND: The optimal haemoglobin threshold for use of red blood cell (RBC) transfusions in anaemic patients remains an active area of research. Blood is a limited resource, and there are concerns about risks, including transmitted infections. If a liberal transfusion strategy does not improve clinical outcomes, or if it is equivalent, then adopting a more restrictive approach should be recognised as the standard of care.

OBJECTIVES: The aim of this review update was to compare 30-day mortality and other clinical outcomes for participants randomised to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all clinical conditions. The restrictive transfusion threshold uses a lower haemoglobin concentration as a threshold for transfusion (most commonly, 7.0 g/dL to 8.0 g/dL), and the liberal transfusion threshold uses a higher haemoglobin concentration to direct transfusion (most commonly, 9.0 g/dL to 10.0 g/dL). Increasingly, investigators are considering other strategies including physiological triggers (i.e. central venous oxygen saturation), alone or in combination with such thresholds, to determine when a transfusion is indicated, so it is important to assess this growing body of evidence in tandem.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Transfusion Evidence Library, Web of Science Conference Proceedings Citation Index, trial registries and PubMed on 14 October 2024. We checked reference lists of published reviews and papers for additional trials.

SELECTION CRITERIA: We included randomised trials of surgical or medical participants that recruited adults or children. We excluded studies that focused on preterm neonates. Eligible trials assigned intervention groups based on different transfusion strategies or thresholds, usually defined by a haemoglobin concentration below which a RBC transfusion would be administered. We included trials in which investigators had allocated participants to higher thresholds or more liberal transfusion strategies compared to more restrictive ones, which might include no transfusion.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We pooled risk ratios across trials using a random-effects model. We assessed risk of bias using the Cochrane RoB 1 tool, and assessed the certainty of evidence using GRADE. We defined participants randomly allocated to the lower transfusion threshold as being in the 'restrictive transfusion' group and those randomly allocated to the higher transfusion threshold as being in the 'liberal transfusion' group.

MAIN RESULTS: Adult threshold comparison We included 61 trials (27,639 participants), across a range of clinical contexts: orthopaedic, cardiac or vascular surgery; critical care; neurocritical care; gastrointestinal bleeding; trauma; acute myocardial infarction; haematological malignancies and postpartum haemorrhage. The haemoglobin concentration used to define the restrictive transfusion group in most trials was between 7.0 g/dL and 8.0 g/dL. The main outcomes were exposure to blood transfusion, 30-day mortality, neurologic function, myocardial infarction, congestive heart failure, cerebral vascular accident, infection and thromboembolism. Studies were generally at low risk of bias. Restrictive transfusion strategies reduced the risk of receiving at least one RBC transfusion by 42% when combining all clinical contexts (risk ratio (RR) 0.58, 95% confidence interval (CI) 0.52 to 0.65; high-certainty evidence), with a large amount of heterogeneity between trials (I² = 97%), reflecting diversity in the strength of estimates, not the efficacy of the policy. When combining all clinical contexts, restrictive transfusion strategies did not modify the risk of 30-day mortality compared with liberal transfusion strategies (RR 1.01, 95% CI 0.90 to 1.14; 44 studies, 22,575 participants; high-certainty evidence) or any of the other outcomes assessed including myocardial infarction, stroke, thromboembolism or infection (moderate to high-certainty evidence). There were two exceptions in clinical populations. In gastrointestinal bleeding, 30-day mortality was lower with a restrictive transfusion strategy (RR 0.63, 95% CI 0.42 to 0.95; 4 studies, 1574 participants). In critically ill patients with brain injury, unfavourable neurological outcome at 6 to 12 months was lower with a liberal transfusion strategy (RR 1.14, 95% CI 1.05 to 1.22; 4 studies, 2297 participants) (moderate-certainty evidence). Transfusion-specific reactions are uncommon, but occurred more frequently with the liberal strategy (Peto odds ratio 0.47, 95% CI 0.36 to 0.62; 18 studies, 11,505 participants). Paediatric threshold comparison We included eight trials (2764 participants), across a limited range of clinical contexts (critical care, cardiac surgery, haematological malignancies and severe malarial anaemia). The haemoglobin concentration used to define the restrictive group in critical care and haematological malignancies trials was between 6.5 g/dL and 8.0 g/dL, and between 7.0 g/dL and 9 g/dL in cardiac surgery trials, depending on the cardiac abnormality and stage of repair. Studies were generally at low risk of bias. There was no clear difference in 30-day mortality between restrictive and liberal transfusion strategies, although confidence intervals were wide (RR 1.22, 95% CI 0.72 to 2.08; 7 studies, 2571 participants; low-certainty evidence). There was moderate-certainty evidence of no clear difference between threshold strategies for infection; very low-certainty evidence of little to no difference for thrombosis and very low-certainty evidence of little to no difference for the outcomes multiple organ dysfunction and cerebrovascular accident. Physiological triggers Nine trials in adults (3818 participants) and one trial in children (100 participants) were identified. These tested different interventions and measures of physiological parameters in diverse clinical populations. The risk of bias was variable. Meta-analysis was not appropriate due to heterogeneity.

AUTHORS' CONCLUSIONS: A restrictive transfusion strategy significantly decreased the proportion of adults and children exposed to RBC transfusion. In most clinical contexts, there was no evidence of harm from a restrictive compared with a liberal transfusion strategy. Neurocritically ill patients, however, have better neurological outcomes at 6 to 12 months with a liberal transfusion strategy. Further work is needed to improve our understanding of outcomes beyond mortality, and to what degree the optimal strategies for transfusion should be modified in some patient populations, including different types of acute bleeding, cancers and subgroups of patients with myocardial infarction and other neurological injuries. New studies need to recognise the clinical context and the limitations of the adoption of a single threshold of haemoglobin, and to consider evaluating the use of physiological parameters to modify transfusion.

Funding

Competing interests

We have considered disclosures relevant to this review. Jeffrey Carson reports being the chief investigator on four trials included in this review (Carson 1998; Carson 2011 (FOCUS); Carson 2013 (MINT pilot); Carson 2023a (MINT)). He has received multiple grants supporting his institution from the US National Institutes of Health. He has been involved with guideline development for red cell transfusions in the Association for the Advancement of Blood & Biotherapies (AABB). He has received travel expenses and an honorarium from Bristol Myer for attending a meeting and giving a lecture. He chaired a Data and Safety Monitoring Board (DSMB) for a trial sponsored by Cerus, for which he received travel expenses and an honorarium. Carolyn Dorée: nothing to declare. Dean Fergusson reports being an author on five completed trials included within this review (Hébert 1999 (TRICC); Mazer 2017 (TRICS III) (TRICS III); Shehata 2012; English 2024 (SAHaRA); Turgeon 2024 (HEMOTION)). He was a Co‐Principal Investigator on the TRICSIII trial (Mazer 2017 (TRICS III)); he was a member of the Steering Committee for the MINT trial (Carson 2023a (MINT)). Paul Hébert reports being an author on four completed trials identified in this review (Hébert 1995 (TRICC pilot); Hébert 1999 (TRICC); Lacroix 2007 (TRIPICU); Carson 2023a (MINT)). He was the lead investigator on the study NCT02619136, the Canadian pilot study for MINT (Carson 2023a (MINT)) for which he was a member of the Executive Committee; he has published six non‐Cochrane reviews in this area. He serves on a guideline panel for the American College of Chest Physicians (ACCP) and has written several editorials for leading journals concerning transfusion triggers. Nareg Roubinian: nothing to declare. Simon Stanworth reports being an author on four included studies. He is the chief investigator on one (Stanworth 2020 (REDDS)); a co‐investigator on another (New 2025 (RePAST)) and a researcher and co‐author on two others (Gillies 2020 (RESULT‐NOF) and Morton 2022 (REAL pilot)); he is a co‐investigator on one ongoing study (Mo 2024) and contributes to another (POPTICCA; NCT03871244). He has received funding through institutions for RBC transfusion trials, including three in patients with haematological malignancy (with no direct funding). He has published four Cochrane and non‐Cochrane systematic reviews in this area, and is an Editor in a Cochrane thematic group; however, he has had no involvement in the editorial process for this review. He is a member of the AABB/International red cell transfusion guideline committee. He is employed by NHSBT, a national blood service, that collects blood for processing and issuing to hospitals. He is current Chair of the International Collaboration for Transfusion Medicine Guidelines (ICTMG). Jane Dennis: membership of AABB/International RBC guideline committee. Marialena Trivella: position of Statistical Editor in a Cochrane thematic group. MT has, however, had no involvement in the editorial process for this review. Monica Pagano: membership of AABB RBC guideline committee. She has received travel expenses and an honorarium from the European Haematology Association (EHA) to attend their annual meeting. Stacey Valentine ‐ membership of AABB RBC guideline committee. Alexis Turgeon reports being an author on two included studies (as chief investigator on Turgeon 2024 (HEMOTION) and author on English 2024 (SAHaRA)). He is also the Director of Cochrane Canada Francophone; however, he has had no involvement in the editorial process for this review. He is the chair holder of the Canada Research Chair in Critical Care Neurology and Trauma. All data extraction and decisions on risk of bias assessments were made by review authors not involved in the trials as researchers.

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Guiding red blood cell transfusions using transfusion limits and other methods

Abstract

Funding

Competing interests

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