Larger versus smaller red blood cell volume per transfusion in hospitalized adults, children and preterm neonates.

rationaleWhile substantial research has evaluated the safety of hemoglobin thresholds and storage length for red blood cell (RBC) transfusion, there is minimal literature on RBC transfusion volume per transfusion event in hospitalized patients. The Choosing Wisely initiative has made a recommendation to transfuse a single unit of RBC per transfusion event, although this is based on little evidence. No recommendation has been made for pediatrics. This review evaluates the effect of the volume of RBC transfusion, administered when the decision has been made to transfuse a hospitalized patient, on mortality and other important outcomes.

objectivesTo compare the effectiveness and safety of larger versus smaller RBC volume per transfusion for anemia in hospitalized adults, children, and preterm neonates. SEARCH

methodsWe searched Evidence-Based Medicine Reviews (EBMR; including CENTRAL), MEDLINE, Embase, Web of Science, and other databases on 5 August 2025, with reference checking, citation searching and contacting study authors to identify additional studies. ELIGIBILITY CRITERIA: Eligible studies were randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) that included adults, children or neonates and compared a larger volume of RBC per transfusion event (intervention) to a smaller volume of RBC transfusion (control). We defined a transfusion event as a single administration of blood products within six hours. OUTCOMES: The critical outcome was mortality. Important outcomes were length of hospital stay, hospital-free days, transfusion-associated adverse events (TAAE), organ dysfunction, number of RBCs transfused, rebleeding and allogeneic donor exposure. RISK OF BIAS: We assessed risk of bias using the Cochrane RoB 2 tool for RCTs and the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) version 2 tool for NRSIs. SYNTHESIS

methodsTwo authors independently extracted data from included studies and assessed the risks of bias. We analyzed data from the included RCTs and NRSIs separately. We used the risk ratio (RR) and mean difference (MD) for pooled effects, using a random-effects model to account for heterogeneity between studies. We used GRADE to assess the certainty of evidence. INCLUDED STUDIES: We included 12 studies (5478 participants); five RCTs, and seven controlled NRSIs. Nine studies included adults (1945 participants), one included children (3199 participants) and two included preterm neonates (334 participants). Eight of the adult studies' participants were in hematology wards or bone marrow transplant units, and one study included postpartum participants. The pediatric study included anemic children, and the neonatal studies included preterm infants < 32 weeks' gestation or weighing < 1.5 kg. All adult studies compared two units of RBCs to one unit of RBCs per transfusion event. The pediatric study compared 15 mL/kg to 10 mL/kg RBCs, and the neonatal studies compared 20 mL/kg to 10 mL/kg RBCs. The included RCTs ranged from low to high risk of bias and the NRSIs ranged from low to critical risk of bias. SYNTHESIS OF

resultsNine studies reported on mortality, although the definition of time of death varied. Meta-analysis of adult studies demonstrated no difference in mortality between the two-unit RBC transfusion group and the one-unit RBC transfusion group in RCTs (RR 1.29, 95% CI 0.62 to 2.67; 2 RCTs, 322 participants; low-certainty evidence) or in NRSIs (RR 1.03, 95% CI 0.62 to 1.71; 5 NRSIs, 1198 participants; low-certainty evidence). There was no difference in hospital length of stay between the two-unit RBC group and the one-unit RBC group in RCTs (MD 0.08, 95% CI -0.66 to 0.82; 2 RCTs, 311 participants; low-certainty evidence) and in NRSIs (MD -0.15, 95% CI -1.68 to 1.38; 4 NRSIs, 1048 participants; very low-certainty evidence). No studies reported hospital-free days as an outcome. There was no difference in TAAEs between the two-unit RBC group and the one-unit RBC group for RCTs (RR 1.25, 95% CI 0.61 to 2.56; 3 RCTs, 388 participants; low-certainty evidence) or NRSIs (RR 0.74, 95% CI 0.30 to 1.82; 3 NRSIs, 546 participants; very low-certainty evidence). During their hospital stay, participants in the two-unit RBC transfusion group received more RBC units than those in the one-unit RBC transfusion group in the NRSIs (MD 0.65 units, 95% CI 0.55 to 0.75; 4 NRSIs, 1064 participants; low-certainty evidence). However, no difference was seen between groups in the RCTs (MD 0.90 units, 95% CI 0.68 to 1.11; 3 RCTs, 378 participants; low-certainty evidence). During each transfusion event, patients in the two-unit RBC transfusion group received 0.66 RBC units more compared to those in the one-unit RBC group (MD 0.66 units, 95% CI 0.59 to 0.73; 3 NRSIs, 791 participants), reflecting adherence to the intervention. There was no difference between the two RBC transfusion groups' rates of thrombosis reported in RCTs (RR 2.26, 95% CI 0.51 to 9.95; 2 RCTs, 311 participants; very low-certainty evidence). No NRSIs reported rates of thrombosis. There was no difference between the two RBC transfusion groups' rebleeding rates in either RCTs (RR 0.52, 95% CI 0.16 to 1.68; 1 RCT, 245 participants; moderate-certainty evidence) or NRSIs (RR 0.64, 95% CI 0.36 to 1.14; 3 studies, 585 participants; very low-certainty evidence). No studies reported on allogenic donor exposure. AUTHORS'

conclusionsIn adults, when comparing two units of RBCs (larger volume) to one unit of RBCs (smaller volume) for a single transfusion event, there was no difference in mortality, length of hospital stay or TAAEs, albeit with low or very low-certainty evidence. However, it reduced the number of required RBC units. The results indicate that a larger transfusion volume confers no clinical benefit over a smaller, more restrictive transfusion strategy (lower transfusion volume), but may lead to a higher amount of blood administered. Given the adverse events associated with RBC transfusion and the resource limitation of the allogeneic blood supply, it is reasonable to support the recommendations for single unit RBC transfusion per transfusion event in adults. In children, evidence is still too limited to be able to make a recommendation on an RBC volume.

fundingThis study did not receive funding. REGISTRATION: This review protocol was previously published with the Cochrane database of systematic reviews (DOI 10.1002/14651858.CD015898).