Liberal Transfusion Thresholds Research Articles

Abstract 4131460: Restrictive or Liberal Blood Transfusion in Patients with Myocardial Infarction and Renal Insufficiency

Background: Chronic kidney disease (CKD) is associated with risk of myocardial infarction (MI) and anemia. Among patients with CKD and anemia who experience MI, it remains uncertain if a liberal transfusion threshold (LTT) strategy (hemoglobin cutoff [Hgb] < 10 g/dL) is superior to a restrictive transfusion threshold (RTT, Hgb 7-8 g/dL) strategy. Objectives: To evaluate outcomes of those with CKD randomized to RTT vs. LTT in the Myocardial Ischemia and Transfusion (MINT) trial (NCT02981407). Methods: Among 3,495 MINT participants with non-missing creatinine (99.7%), we compared the baseline characteristics and outcomes at 30 days post-randomization of those individuals without CKD (N = 1279), CKD with eGFR 30-60 mL/min/1.73 m 2 (N = 999), CKD with eGFR < 30 mL/min/1.73 m 2 (N = 802), and CKD requiring dialysis (N = 415), both overall and by randomized transfusion strategy. Interaction terms for eGFR category by treatment assignment on each outcome were assessed. Results: Individuals with CKD compared to those without CKD more frequently presented with NSTEMI (all p < 0.001) and had a greater risk of all-cause death, recurrent MI, rehospitalization, and heart failure (all p < 0.05). Compared to a liberal transfusion strategy, a restrictive strategy among non-dialysis dependent individuals with an eGFR < 30 mL/min/1.73 m 2 was associated with an increased risk of death/recurrent MI ( Figure 1 ) and unplanned rehospitalization ( Figure 2 ). Among individuals with an eGFR 30-60 mL/min/1.73 m 2 , a restrictive strategy was associated with an increased risk of cardiac death ( Figure 1 ). No eGFR category by treatment assignment interaction terms were significant. Conclusions: In this prespecified analysis, individuals with CKD were at greater risk of death, recurrent MI, heart failure, and unplanned rehospitalization at 30 days post-randomization than those without CKD. In individuals with CKD, a restrictive transfusion strategy was associated with increased risk of adverse outcomes.

A liberal blood transfusion strategy is safe in patients with myocardial infarction, anemia, and heart failure: lessons from MINT

Abstract Background In patients with acute myocardial infarction (MI) and anemia, the Myocardial Ischemia and Transfusion (MINT) trial found a trend toward increased 30-day death or recurrent MI with a restrictive compared with a liberal blood transfusion strategy. Patients with and without heart failure (HF) may respond differently to blood transfusion. Purpose To characterize the effects of restrictive vs. liberal transfusion strategies on clinical outcomes in patients with MI and anemia with and without baseline HF. Methods In the MINT trial, 3504 patients with MI and hemoglobin <10 g/dL were randomized to restrictive (7-8 g/dL) or liberal (10 g/dL) transfusion thresholds. We compared outcomes between patients with and without baseline HF, defined as any history of HF, acute HF, or baseline left ventricular ejection fraction (LVEF) <45%. Outcomes included death or incident HF, death or recurrent MI, death, and incident HF, all at 30 days. Results Compared with patients without baseline HF (n=1633), patients with baseline HF (overall n=1871 (history of HF n=1066, acute HF n=780, LVEF <45% n= 1099) were older, more frequently male and Black, and had higher rates of prior PCI, diabetes, and hypertension. In the restrictive strategy, patients with and without baseline HF received an average of 0.63 and 0.80 units of blood and had a median LOS of 6 and 4 days, respectively. In the liberal strategy, patients with and without baseline HF received an average of 2.44 and 2.49 units of blood and had a median LOS of 5 and 4 days, respectively. Patients with baseline HF had higher rates of death or incident HF (18.0% vs. 10.0%, risk ratio [RR]=1.79 [95% confidence interval {CI} 1.50-2.13]), death or recurrent MI (17.6% vs. 13.5%, RR=1.31 [95% CI 1.12-1.53]), and death (10.5% vs. 7.5%, RR 1.41 [95% CI 1.14-1.75]). Among patients with baseline HF, a restrictive transfusion strategy resulted in a trend toward an increase in death or HF and death or MI compared with a liberal transfusion strategy (Table, Figure). Among patients without baseline HF, the risk of incident HF was lower with restrictive than with liberal transfusion strategy. Conclusions Among patients with MI and anemia, a restrictive transfusion strategy resulted in a greater increase in death or HF, death or MI, and death in patients with baseline HF than in patients without baseline HF. A liberal transfusion strategy is safe for patients with MI and anemia, including those with prior or acute HF.TableFigure

Generalizability of SELECT to a contemporary cohort of cardiac surgical patients: analysis of the TRICS III Randomized Trial

Abstract Background The SELECT trial reported a significant reduction in cardiovascular (CV) outcomes with semaglutide amongst patients without diabetes who had pre-existing CV disease and a body-mass index (BMI) of 27 or greater. Patients undergoing cardiac surgery represent a high-risk subset of those with established CV disease, and may benefit from treatment with semaglutide. Purpose This study evaluated the generalizability of SELECT to a contemporary international cohort of cardiac surgical patients, and assessed whether differences between SELECT-eligible and non-eligible patients translated to altered risks of CV outcomes. Methods Present data was gathered from the TRICS III trial, a multicentre, randomized trial of restrictive versus liberal red-cell transfusion thresholds amongst 5243 cardiac surgical patients with a EuroSCORE I of ≥6. The proportion of cardiac surgical patients eligible for SELECT was determined by applying its selection criteria to the TRICS III cohort. Finally, baseline characteristics and outcomes stratified by SELECT eligibility were compared. Results A total of 4887 patients from the TRICS III cohort had available data for analysis, of which 452 (9.2%) were deemed to have been eligible for the SELECT trial. A comparison of baseline characteristics between SELECT-eligible and non-eligible patients are presented in Table 1; while SELECT-eligible patients were more likely to have preserved left ventricular function (71.7% vs. 61.0%), EuroSCORE I values were comparable between the two groups (7.8±2.1 vs. 7.9±1.9). The rate of a 3-point MACCE of Death, MI or stroke in the present cohort of SELECT-eligible patients undergoing cardiac surgery (16.6%) was numerically higher than those enrolled in SELECT receiving semaglutide (8.1%) or placebo (10.0%), despite the shorter follow-up (6 months vs. 39.8 months). Six month outcomes following cardiac surgery were similar regardless of SELECT eligibility (Figure 1); no difference in risk of outcomes was documented for the 3-point MACCE [SELECT Eligible vs. Non-eligible – 16.6% vs. 14.5%; OR 1.17 (0.9-1.53); P=0.24] and the TRICS III primary composite of Death, MI, Stroke, or New-Onset Renal Failure with Dialysis [17.0% vs. 17.0%; OR 1.0 (0.77-1.29); P=0.98]. There was a trend towards higher rates of MI at 6 months amongst SELECT-eligible patients, but this difference failed to reach statistical significance [8.5% vs. 6.3%; OR 2.0 (0.96-1.39); P=0.08). Conclusions In this large international cohort of contemporary cardiac surgical patients, nearly 10% would have met eligibility for SELECT. SELECT-eligible patients undergoing cardiac surgery in TRICS III had a numerically higher rate of MACCE than those enrolled in SELECT, highlighting the high risk nature of this patient subgroup. However, amongst SELECT-eligible and non-eligible patients undergoing cardiac surgery, no significant difference in CV outcomes was uncovered.

Red Blood Cell Transfusion in European Neonatal Intensive Care Units, 2022 to 2023

Red blood cell (RBC) transfusions are frequently administered to preterm infants born before 32 weeks of gestation in the neonatal intensive care unit (NICU). Two randomized clinical trials (Effects of Transfusion Thresholds on Neurocognitive Outcomes of Extremely Low-Birth-Weight Infants [ETTNO] and Transfusion of Prematures [TOP]) found that liberal RBC transfusion thresholds are nonsuperior to restrictive thresholds, but the extent to which these results have been integrated into clinical practice since publication in 2020 is unknown. To describe neonatal RBC transfusion practice in Europe. This international prospective observational cohort study collected data between September 1, 2022, and August 31, 2023, with a 6-week observation period per center, from 64 NICUs in 22 European countries. Participants included 1143 preterm infants born before 32 weeks of gestation. Admission to the NICU. Study outcome measures included RBC transfusion prevalence rates, cumulative incidence, indications, pretransfusion hemoglobin (Hb) levels, volumes, and transfusion rates, Hb increment, and adverse effects of RBC transfusion. A total of 1143 preterm infants were included (641 male [56.1%]; median gestational age at birth, 28 weeks plus 2 days [IQR, 26 weeks plus 2 days to 30 weeks plus 2 days]; median birth weight, 1030 [IQR, 780-1350] g), of whom 396 received 1 or more RBC transfusions, totaling 903 transfusions. Overall RBC transfusion prevalence rate during postnatal days 1 to 28 was 3.4 transfusion days per 100 admission days, with considerable variation across countries, only partly explained by patient mix. By day 28, 36.5% (95% CI, 31.6%-41.5%) of infants had received at least 1 transfusion. Most transfusions were given based on a defined Hb threshold (748 [82.8%]). Hemoglobin levels before transfusions indicated for threshold were below the restrictive thresholds set by ETTNO in 324 of 729 transfusions (44.4%) and TOP in 265 of 729 (36.4%). Conversely, they were between restrictive and liberal thresholds in 352 (48.3%) and 409 (56.1%) transfusions, respectively, and above liberal thresholds in 53 (7.3%) and 55 (7.5%) transfusions, respectively. Most transfusions given based on threshold had volumes of 15 mL/kg (470 of 738 [63.7%]) and were administered over 3 hours (400 of 738 [54.2%]), but there was substantial variation in dose and duration. In this cohort study of very preterm infants, most transfusions indicated for threshold were given for pretransfusion Hb levels above restrictive transfusion thresholds evaluated in recent trials. These results underline the need to optimize practices and for implementation research to support uptake of evidence.

Orthopaedic Trauma and Anemia: Conservative versus Liberal Transfusion Strategy: A Prospective Randomized Study

OBJECTIVES: To determine whether it is safe to use a conservative packed red blood cell transfusion hemoglobin (Hgb) threshold (5.5 g/dL) compared with a liberal transfusion threshold (7.0 g/dL) for asymptomatic musculoskeletal injured trauma patients who are no longer in the initial resuscitative period. METHODS: Design: Prospective, randomized, multicenter trial. Setting: Three level 1 trauma centers. Patient Selection Criteria: Patients aged 18–50 with an associated musculoskeletal injury with Hgb less than 9 g/dL or expected drop below 9 g/dL with planned surgery who were stable and no longer being actively resuscitated were randomized once their Hgb dropped below 7 g/dL to a conservative transfusion threshold of 5.5 g/dL versus a liberal threshold of 7.0 g/dL. Outcome Measures and Comparisons: Postoperative infection, other post-operative complications and Musculoskeletal Functional Assessment scores obtained at baseline, 6 months, and 1 year were compared for liberal and conservative transfusion thresholds. RESULTS: Sixty-five patients completed 1 year follow-up. There was a significant association between a liberal transfusion strategy and higher rate of infection (P = 0.01), with no difference in functional outcomes at 6 months or 1 year. This study was adequately powered at 92% to detect a difference in superficial infection (7% for liberal group, 0% for conservative, P < 0.01) but underpowered to detect a difference for deep infection (14% for liberal group, 6% for conservative group, P = 0.2). CONCLUSIONS: A conservative transfusion threshold of 5.5 g/dL in an asymptomatic young trauma patient with associated musculoskeletal injuries leads to a lower infection rate without an increase in adverse outcomes and no difference in functional outcomes at 6 months or 1 year. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

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.

Blood Transfusions and Adverse Events after Colorectal Surgery: A Propensity-Score-Matched Analysis of a Hen–Egg Issue

Blood transfusions are considered a risk factor for adverse outcomes after colorectal surgery. However, it is still unclear if they are the cause (the hen) or the consequence (the egg) of adverse events. A prospective database of 4529 colorectal resections gathered over a 12-month period in 76 Italian surgical units (the iCral3 study), reporting patient-, disease-, and procedure-related variables, together with 60-day adverse events, was retrospectively analyzed identifying a subgroup of 304 cases (6.7%) that received intra- and/or postoperative blood transfusions (IPBTs). The endpoints considered were overall and major morbidity (OM and MM, respectively), anastomotic leakage (AL), and mortality (M) rates. After the exclusion of 336 patients who underwent neo-adjuvant treatments, 4193 (92.6%) cases were analyzed through a 1:1 propensity score matching model including 22 covariates. Two well-balanced groups of 275 patients each were obtained: group A, presence of IPBT, and group B, absence of IPBT. Group A vs. group B showed a significantly higher risk of overall morbidity (154 (56%) vs. 84 (31%) events; OR 3.07; 95%CI 2.13-4.43; p = 0.001), major morbidity (59 (21%) vs. 13 (4.7%) events; OR 6.06; 95%CI 3.17-11.6; p = 0.001), and anastomotic leakage (31 (11.3%) vs. 8 (2.9%) events; OR 4.72; 95%CI 2.09-10.66; p = 0.0002). No significant difference was recorded between the two groups concerning the risk of mortality. The original subpopulation of 304 patients that received IPBT was further analyzed considering three variables: appropriateness of BT according to liberal transfusion thresholds, BT following any hemorrhagic and/or major adverse event, and major adverse event following BT without any previous hemorrhagic adverse event. Inappropriate BT was administered in more than a quarter of cases, without any significant influence on any endpoint. The majority of BT was administered after a hemorrhagic or a major adverse event, with significantly higher rates of MM and AL. Finally, a major adverse event followed BT in a minority (4.3%) of cases, with significantly higher MM, AL, and M rates. In conclusion, although the majority of IPBT was administered with the consequence of hemorrhage and/or major adverse events (the egg), after adjustment accounting for 22 covariates, IPBT still resulted in a definite source of a higher risk of major morbidity and anastomotic leakage rates after colorectal surgery (the hen), calling urgent attention to the implementation of patient blood management programs.

Comparative efficacy and safety of restrictive versus liberal transfusion thresholds in anemic preterm infants: a meta-analysis of 12 randomized controlled trials

The comparative efficacy and safety of restrictive with liberal transfusion thresholds remain controversial in anemic preterm infants. This meta-analysis aimed to compare the efficacy and safety of these two transfusion thresholds for anemic preterm infants. We searched PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) for relevant randomized controlled trials (RCTs) comparing restrictive with liberal transfusion thresholds in anemic preterm infants through April 30, 2022. Two independent investigators screened literature, extracted data, and appraised the methodological quality of eligible studies. Meta-analysis was conducted using RevMan version 5.3.5. Twelve RCTs with 4380 preterm infants were included. Liberal transfusion threshold significantly increased the level of hemoglobin after transfusion (mean difference (MD): −10.03; 95% confidence interval (CI): −15.98 to −4.08; p=0.001; I2=94%) and hematocrit (MD: −3.62; 95%CI: −6.78 to −0.46; p=0.02; I2=80%) compared with restrictive transfusion. Infants’ age at first transfusion in restrictive transfusion group was higher than that of infants in liberal transfusion group (MD: 5.08; 95%CI: 2.27 to7.89; p=0.004; I2=54%); however, restrictive transfusion was associated with more time on supplemental oxygen (MD: 3.56; 95%CI: 1.93 to 5.18; p<0.001; I2=62%) and ventilator or CPAP (MD: 3.31; 95%CI: 1.42 to 5.20; p=0.006; I2=75%). For the remaining outcomes, two transfusion strategies were comparable. Furthermore, a series of sensitivity analyses confirmed the robustness of the level of hemoglobin after transfusion, age at first transfusion, time on ventilator or CPAP, and safety outcomes. Evidence with substantial heterogeneity indicates that liberal and restrictive transfusion thresholds are effective and safe blood cell transfusion strategies in anemic preterm infants, but the liberal strategy may be more effective in shortening the length of necessary respiratory support.

Transfusion Guidelines in Traumatic Brain Injury: A Systematic Review and Meta-Analysis of the Currently Available Evidence.

Our study aims to provide a synthesis of the best available evidence on the hemoglobin (hgb) red blood cell (RBC) transfusion thresholds in adult traumatic brain injury (TBI) patients, as well as describing the risk factors and outcomes associated with RBC transfusion in this population. A systematic review and meta-analysis was conducted using PubMed, Google Scholar, and Web of Science electronic databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess articles discussing RBC transfusion thresholds and describe complications secondary to transfusion in adult TBI patients in the perioperative period. Fifteen articles met search criteria and were reviewed for analysis. Compared to non-transfused, TBI patients who received transfusion tended to be primarily male patients with worse Injury Severity Score (ISS) and Glasgow Coma Scale. Further, the meta-analysis corroborated that transfused TBI patients are older (p = 0.04), have worse ISS scores (p = 0.001), receive more units of RBCs (p = 0.02), and have both higher mortality (p < 0.001) and complication rates (p < 0.0001). There were no differences identified in rates of hypertension, diabetes mellitus, and Abbreviated Injury Scale scores. Additionally, whereas many studies support restrictive (hgb <7 g/dL) transfusion thresholds over liberal (hgb <10 g/dL), our meta-analysis revealed no significant difference in mortality between those thresholds (p = 0.79). Current Class B/C level III evidence predominantly recommends against a liberal transfusion threshold of 10 g/dL for TBI patients (Class B/C level III), but our meta-analysis found no difference in survival between groups. There is evidence suggesting that an intermediate threshold between 7 and 9 g/dL, reflecting the physiological oxygen needs of cerebral tissue, may be worth exploring.

Transfusion thresholds in cardiac surgery: Commentary on Bracey et al., 1999.

Transfusion thresholds in cardiac surgery: Commentary on Bracey et al., 1999.

Impact of restrictive red blood cell transfusion strategy on thrombosis-related events: A meta-analysis and systematic review.

There is an ongoing controversy regarding the risks of restrictive and liberal red blood cell (RBC) transfusion strategies. This meta-analysis assessed whether transfusion at a lower threshold was superior to transfusion at a higher threshold, with regard to thrombosis-related events, that is, whether these outcomes can benefit from a restrictive transfusion strategy is debated. We searched PubMed, Cochrane Central Register of Controlled Trials and Scopus from inception up to 31 July 2021. We included randomized controlled trials (RCTs) in any clinical setting that evaluated the effects of restrictive versus liberal RBC transfusion in adults. We used random-effects models to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) based on pooled data. Thirty RCTs involving 17,334 participants were included. The pooled RR for thromboembolic events was 0.65 (95% CI 0.44-0.94; p= 0.020; I2 = 0.0%, very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR=0.83; 95% CI 0.64-1.09; p= 0.180; I2 = 0.0%, very low-quality evidence) or myocardial infarction (RR=1.05; 95% CI 0.87-1.26; p= 0.620; I2 = 0.0%, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced (1) thromboembolic events in RCTs conducted in North America and (2) myocardial infarctions in the subgroup of RCTs where the restrictive transfusion threshold was 7g/dl but not in the 8g/dl subgroup (with a liberal transfusion threshold of 10g/dl in both subgroups). A restrictive (relative to liberal) transfusion strategy may be effective in reducing venous thrombosis but not arterial thrombosis.

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. Mixed method approach combining multicenter retrospective study and survey. Sixteen ICUs worldwide. Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. None. The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

Transfusion thresholds for guiding red blood cell transfusion.

Transfusion thresholds for guiding red blood cell transfusion.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients.

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.

Patient Blood Management

Impact Statement: Patient blood management (PBM) recommendations can help providers manage anemia and assist in transfusion-related decision-making. Introduction: Blood transfusions are often a necessary treatment for operative patients, but they are not without potential complications, including hemolytic reactions, and even death. Establishing parameters and guidelines for transfusions in patients undergoing an operation is imperative in treating them safely and effectively; patient blood management protocols provide these guidelines. Literature review: Patient blood management (PBM) is based on three pillars: treatment of underlying anemia, minimizing blood loss, and the use of transfusion thresholds. Establishing hemoglobin levels that dictate transfusion thresholds can be either restrictive (transfusing at lower thresholds) or liberal (transfusing at higher thresholds). Current literature recommends restrictive transfusion thresholds (hemoglobin less than 7 gm/dL) with consideration for individual patient status. Description of the case: A 56-year old male underwent an emergent exploratory laparotomy to locate a source of bleeding four days after having a hemicolectomy. He received one unit of packed red blood cells (PRBCs) in the intensive care unit overnight and arrived in the operating room (OR) on a phenylephrine drip. After induction, the patient required a vasopressin drip as well. The patient remained hemodynamically unstable and his hemoglobin was 9.8 g/dL, thus, the decision was made to administer one unit of PRBCs in the OR. The patient remained unstable throughout the case and a hemoglobin recheck was 9.5 g/dL, so a second unit of PRBCs was given. The transfusion threshold utilized in this case was liberal (less than 10 g/dL). Discussion and conclusions: In this case, all three pillars of PBM were taken into account. Pre-operative anemia was treated with a blood transfusion. Determining the cause and providing treatment of anemia before surgery can help decrease the need for transfusions. There was minimal intraoperative blood loss during the case, however techniques to manage this potential complication include: cell saver, hemodilution, and goal-directed fluid therapy. Finally, a liberal transfusion threshold was found appropriate as the patient was hemodynamically unstable. A lower transfusion threshold (less than 7 g/dL) is generally recommended for stable patients. Utilization of PBM can help guide transfusion decision-making and decrease the number of blood products given without increasing patient morbidity or mortality.

Current Controversy on Platelets and Patent Ductus Arteriosus Closure in Preterm Infants.

Platelets are critically involved in murine patent ductus arteriosus (PDA) closure. To date, the clinical significance of these findings in human preterm infants with PDA is still controversial. We discuss the available study data on the role of platelets for PDA closure in preterm infants: Several mostly retrospective studies have yielded conflicting results on whether thrombocytopenia contributes to failed spontaneous ductal closure. The same applies to investigations on the role of thrombocytopenia as a risk factor for unsuccessful ductus arteriosus closure by pharmacological treatment with cyclooxygenase inhibitors. Nonetheless, recent meta-analyses have concluded that thrombocytopenia constitutes an independent risk factor for both failed spontaneous and pharmacological PDA closure in preterm infants. However, the available investigations differ in regard to patient characteristics, diagnostic strategies, and treatment protocols. Several studies suggest that impaired platelet function rather than platelet number is critically involved in failure of ductus arteriosus closure in the preterm infant. A recent randomized-controlled trial on platelet transfusions in preterm infants with PDA failed to show any benefit for liberal vs. restrictive transfusion thresholds on PDA closure rates. Importantly, liberal transfusions were associated with an increased rate of intraventricular hemorrhage, and thus should be avoided. In conclusion, the available evidence suggests that thrombocytopenia and platelet dysfunction contribute to failure of spontaneous and pharmacological PDA closure in preterm infants. However, these platelet effects on PDA seem to be of only moderate clinical significance. Furthermore, platelet transfusions in thrombocytopenic preterm infants in order to facilitate PDA closure appear to cause more harm than good.

Assessing the appropriateness of blood transfusion among injured patients at a Ghanaian tertiary hospital: Time for clarity on the use of a scarce resource.

Hemorrhage is an important cause of preventable injury-related death. Many low- and middle-income country (LMIC) patients do not have timely access to safe blood. We sought to determine the degree of appropriateness of blood transfusion among patients with injuries requiring surgical intervention at presentation to a tertiary hospital in Ghana. We performed a retrospective review of such patients presenting to Komfo Anokye Teaching Hospital (KATH), from January 2015 to December 2016. Patients' hemoglobin levels at presentation were determined as the first record of hemoglobin after presentation and their receipt of blood transfusion was determined by explicit documentation in the chart. We defined appropriate blood transfusion practice as patients receiving transfusion when hemoglobin was equal or below a threshold, or patients not being transfused when hemoglobin was above the threshold. We considered both restrictive (hemoglobin ≤7 g/dL) and liberal (hemoglobin ≤10 g/dL) transfusion thresholds. There were 1,408 patients who presented to KATH with injuries that met inclusion criteria. Two hundred and ninety two (292) patients were excluded because of missing hemoglobin information. Four hundred and fifty eight (458;41%) patients received blood transfusion. Transfused patients had a higher mean age (38 vs 35 years) and were less likely to be male (62% vs 71%). Transfused patients underwent more external fixation procedures (28% vs 19%), trauma amputations (5% vs 1%) and trauma laparotomies (3% vs 1%). At a restrictive transfusion threshold (hemoglobin ≤7 g/dL), 20% of patients who needed a transfusion did not receive one and 39% of patients who did not need a transfusion received one. At a liberal threshold (hemoglobin ≤10 g/dL), 33% of patients who needed a transfusion did not receive one and 30% of patients who did not need a transfusion received one. Blood transfusion practice was inappropriate in 31%-39% of all patients. Our data suggest that clearer guidelines for blood transfusion among emergency surgery patients are needed in Ghana and similar LMICs to avoid inappropriate use of blood as a scarce resource.

Liberal Versus Restrictive Hemoglobin Levels as Thresholds for Blood Transfusions.

Blood transfusion is a common treatment of anemia due to chronic disease or acute blood loss. However, there continues to be uncertainty concerning the appropriate threshold for transfusion. A restrictive protocol could decrease blood administered, transmissible infections, transfusion reactions, volume overload, and utilization of a limited commodity. However, anemia may result in decreased oxygen delivery which could lead to metabolic dysfunction an increased cell death. Determining an appropriate transfusion threshold is thus an important objective. A previous Cochrane review found the use of restrictive thresholds decreased transfusions compared to liberal thresholds. No difference in secondary outcomes, including 30-day mortality, hospital length of stay, cardiac events, and myocardial infarction, was noted.