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Red blood cell (RBC) antigen matching beyond ABO and RhD is commonly recommended for patients with sickle cell disease (SCD) and thalassaemia. We present an updated systematic literature review to inform evidence-based guidelines on RBC matching. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool was used to develop recommendations. Six new observational studies (4 prospective, 2 retrospective) were identified. The six studies reported on 583 patients in total, including cross-over designs, with sample sizes from 10 to 343. Studies were heterogeneous, utilising varying degrees of RBC matching and different definitions for 'extended' matching. All reported on alloimmunisation. One study reported on molecular matching. The reported prevalence of alloimmunisation using limited matching was 0%-50% and with extended matching was 0%-24%. Eighty-two patients were alloimmunised before study entry. The risk of bias across studies was moderate to critical. The guideline panel recommends that ABO, RhDCcEe, and K-compatible RBCs are selected for individuals with SCD and thalassaemia, even in the absence of alloantibodies, and that RBCs which are antigen-negative to already existing clinically significant antibodies are chosen. There is a need for comparative research to define the benefit, impact, cost-effectiveness, and feasibility of extended RBC matching strategies to prevent alloimmunisation., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Blood transfusions, crucial in managing anemia and coagulopathy in intensive care unit (ICU) settings, require accurate prediction for effective resource allocation and patient risk assessment. However, existing clinical decision support systems have primarily targeted a particular patient demographic with unique medical conditions and focused on a single type of blood transfusion. This study aims to develop an advanced machine learning-based model to predict the probability of transfusion necessity over the next 24 h for a diverse range of non-traumatic ICU patients. Methods: We conducted a retrospective cohort study on 72,072 non-traumatic adult ICU patients admitted to a high-volume US metropolitan academic hospital between 2016 and 2020. We developed a meta-learner and various machine learning models to serve as predictors, training them annually with 4-year data and evaluating on the fifth, unseen year, iteratively over 5 years. Results: The experimental results revealed that the meta-model surpasses the other models in different development scenarios. It achieved notable performance metrics, including an area under the receiver operating characteristic curve of 0.97, an accuracy rate of 0.93, and an F1 score of 0.89 in the best scenario. Conclusion: This study pioneers the use of machine learning models for predicting the likelihood of blood transfusion receipt in a diverse cohort of critically ill patients. The findings of this evaluation confirm that our model not only effectively predicts transfusion reception but also identifies key biomarkers for making transfusion decisions., Competing Interests: Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Alireza Rafiei et al.)

Background: Pediatric Patient Blood Management (PBM) programs require continuous surveillance of errors and near misses. However, most PBM programs rely on passive surveillance methods. Our objective was to develop and evaluate a set of automated trigger tools for active surveillance of pediatric PBM errors., Materials and Methods: We used the Rand-UCLA method with an expert panel of pediatric transfusion medicine specialists to identify and prioritize candidate trigger tools for all transfused blood products. We then iteratively developed automated queries of electronic health record (EHR) data for the highest priority triggers. Two physicians manually reviewed a subset of cases meeting trigger tool criteria and estimated each trigger tool's positive predictive value (PPV). We then estimated the rate of PBM errors, whether they reached the patient, and adverse events for each trigger tool across four years in a single pediatric health system., Results: We identified 28 potential triggers for pediatric PBM errors and developed 5 automated trigger tools (positive patient identification, missing irradiation, unwashed products despite prior anaphylaxis, transfusion lasting >4 hours, over-transfusion by volume). The PPV for ordering errors ranged from 38-100%. The most frequently detected near miss event reaching patients was first transfusions without positive patient identification (estimate 303, 95% CI: 288-318 per year). The only adverse events detected were from over-transfusions by volume, including 4 adverse events detected on manual review that had not been reported in passive surveillance systems., Discussion: It is feasible to automatically detect pediatric PBM errors using existing data captured in the EHR that enable active surveillance systems. Over-transfusions may be one of the most frequent causes of harm in the pediatric environment.

Few data describe pediatric patients who receive massive transfusion for life-threatening hemorrhage (LTH) while on extracorporeal membrane oxygenation (ECMO). We present a retrospective secondary analysis of a multicenter prospective observational study to describe resource utilization and mortality in pediatric patients with LTH while on ECMO. Children who were on ECMO during an LTH were compared to children with LTH who were not on ECMO. Primary outcomes were volumes of blood products administered and 28 day mortality. Comparisons were assessed by two-sided Fisher's exact test or Wilcoxon rank sum test. A total of 449 children, including 36 on ECMO, were included. Compared to those not on ECMO, children on ECMO received a higher volume of blood products (110 [50-223] vs . 59 [28-113]) ml/kg, p = 0.002) and were more likely to receive antifibrinolytic therapy (39% vs . 10%, p < 0.001). Blood product ratios were similar. Extracorporeal membrane oxygenation patients had higher 28 day mortality (64% vs. 35%, p = 0.001), although 24 hour mortality was similar (17% vs . 23%, p = 0.5). In conclusion, children on ECMO with LTH experience high resource utilization and 28 day mortality. Studies are needed to identify children at risk for LTH and to evaluate ECMO-specific treatment strategies., Competing Interests: Disclosure: M.E.S. is a consultant for Medtronic education services; P.C.S. is a consultant for Cerus, Hemanext, CSL Behring, and Haima and is founder and chief medical officer for Kalocyte. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Objectives: To assess sex-specific differences in the association between pre-transfusion haemoglobin values and early neurodevelopmental function., Design: Observational follow-up of infants with birth weights <1000 g and gestational ages 22-28 weeks who were enrolled in the NICHD Neonatal Research Network Transfusion of Prematures (TOP) Trial at 19 U.S. sites, 2012-2017., Main Outcome Measures: Pretransfusion haemoglobin values were obtained longitudinally through 36 weeks' postmenstrual age. The infant's mean pretransfusion haemoglobin was used as a marker of degree of anaemia (n=1655 measures). Measures of brain function were obtained at 22-26 months' corrected age using the Bayley Scales of Infant & Toddler Development, third edition (BSID-III) (n=1290 BSID-III scores). Sex-specific estimates for the linear relation between pretransfusion haemoglobin and BSID-III scores were obtained from repeated-measures regression analysis, adjusted for gestational age, birth weight, study site, clinical characteristics, and demographic covariates., Results: The relation of pretransfusion haemoglobin with 24-month BSID-III scores showed significant, independent interactions with both (1) sex (p=0.046) and (2) retinopathy of prematurity (ROP; p=0.004). In 614 males, BSID-III scores were higher by 1.07 points per g/dL (95% CI 1.58 to 4.33; p=0.008), not differing significantly among the three subscales (cognitive, language and motor; p=0.94). In 247 infants with ROP, BSID-III scores were higher by 2.95 points per g/dL (95% CI 0.28 to 1.87; p<0.0001), uniformly across subscales (p=0.73). These associations were non-significant in 676 females (p=0.96) and 1043 infants without ROP (p=0.81)., Conclusions: This study demonstrates sex-specific associations between mean pretransfusion haemoglobin (a marker of the severity of anaemia throughout the neonatal intensive care unit [NICU] hospitalisation) and early neurodevelopmental function at 22-26 months' corrected age., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Post-transfusion survival of donor red blood cells (RBCs) is important for effective chronic transfusion therapy in conditions including sickle cell disease (SCD). Biotin labeling RBCs allows direct in vivo measurement of multiple donor RBC units simultaneously post-transfusion., Study Design and Methods: In an observational trial of patients with SCD receiving monthly chronic transfusion therapy, aliquots of RBCs from one transfusion episode were biotin-labeled and infused along with the unlabeled RBC units. Serial blood samples were obtained to measure RBC survival. Donor units were tested for RBC indices, hemoglobin fractionation, and glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. For microcytic donor RBCs (MCV < 70 fL), HBA1 and HBA2 genetic testing was performed on whole blood., Results: We present one recipient, a pediatric patient with SCD and splenectomy who received two RBC units with aliquots from each unit labeled at distinct biotin densities (2 and 18 μg/mL biotin). One donor unit was identified to have microcytosis (MCV 68.5 fL after biotinylation); whole blood sample obtained at a subsequent donation showed 2-gene deletion alpha-thalassemia trait (ɑ- 3.7kb /ɑ- 3.7kb ) and normal serum ferritin. G6PD activity was >60% of normal mean for both. The RBCs with alpha-thalassemia RBC had accelerated clearance and increased surface phosphatidylserine post-transfusion, as compared with the normocytic RBC (half life 65 vs. 86 days, respectively)., Discussion: Post-transfusion RBC survival may be lower for units from donors with alpha-thalassemia trait, although the impact of thalassemia trait donors on transfusion efficacy requires further study., (© 2024 AABB.)

Importance: Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants., Objective: To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either higher or lower hemoglobin transfusion thresholds., Design, Setting, and Participants: This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023., Exposures: First, the distribution of RBC transfusions and the occurrence of NEC up to postnatal day 60 were examined. Second, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, the risk of NEC in posttransfusion hazard periods was compared with that in pretransfusion control periods, stratifying the risk based on randomization group (higher or lower hemoglobin transfusion threshold group)., Main Outcomes and Measures: The primary outcome was incidence of NEC stage 2 or 3. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, taking into account the number of days at risk., Results: Of 1824 ELBW infants randomized during the TOP trial, 1690 were included in the present analysis (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female). After categorizing 4947 hazard periods and 5813 control periods, we identified 133 NEC cases. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The risk of NEC was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32; P = .74). This risk did not differ significantly between randomization groups, but the incidence rate of NEC per 1000 days peaked between postnatal days 20 and 29 in the lower hemoglobin transfusion threshold group., Conclusions and Relevance: The findings of this post hoc analysis suggest that, among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher risk of NEC during 72-hour posttransfusion hazard periods. Given that the incidence rate of NEC peaked between postnatal days 20 and 29 among infants with lower hemoglobin values, a more in-depth examination of this at-risk period using larger data sets is warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT01702805.

Introduction: Transfusion may increase the risk of organ failure through immunomodulatory effects. The primary objective of this study was to assess for patient or transfusion-related factors that are independently associated with the risk of acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in a cohort of children with life-threatening bleeding from all etiologies., Methods: In a secondary analysis of the prospective observational massive transfusion in children (MATIC) study, multivariable logistic regression was performed in an adjusted analysis to determine if blood product ratios or deficits were independently associated with AKI or ARDS in children with life-threatening bleeding., Results: There were 449 children included with a median (interquartile range, IQR) age of 7.3 years (1.7-14.7). Within 5 days of the life-threatening bleeding event, AKI occurred in 18.5% and ARDS occurred in 20.3% of the subjects. Every 10% increase in the platelet to red blood cell transfusion ratio is independently associated with a 12.7% increase in the odds of AKI (adjusted odds ratio 1.127; 95% confidence interval 1.025-1.239; p-value .013). Subjects with operative or medical etiologies were independently associated with an increased risk of AKI compared to those with traumatic injury. No transfusion-related variables were independently associated with the risk of developing ARDS., Conclusion: The use of increased platelet to red blood cell transfusion ratios in children with life-threatening bleeding of any etiology may increase the risk of AKI but not ARDS. Prospective trials are needed to determine if increased platelet use in this cohort increases the risk of AKI to examine possible mechanisms., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Recent data suggest female sex imparts a survival benefit after trauma in adults. The independent associations between patient sex and age with outcomes have not been examined in children with life-threatening hemorrhage (LTH) from all etiologies., Study Design and Methods: In a secondary analysis of a multicenter prospective observational study of children with LTH, Massive Transfusion in Children (MATIC), we analyzed if patient sex and age were associated with differences in severity of illness, therapies, and outcomes. Primary outcomes were 24 hour mortality and weight-adjusted transfusion volume during LTH. Kruskal-Wallis, chi-square testing, and multivariable linear regression were used for adjusted analyses., Results: Of 449 children, 45% were females and 55% were males. Females were more commonly younger, white, and with less trauma as the etiology of LTH compared to males. Markers of clinical severity were similar between groups, except injury severity score (ISS) was higher in females in the trauma subgroup. In terms of resuscitative practices, females received greater weight-adjusted total transfusion volumes compared to males (76 (40-150) mL/kg vs. 53 (24-100) mL/kg), as well as increased red blood cells (RBCs), plasma, and platelets compared to males. After adjustment for confounders, female sex and age 0-11 years were independently associated with increased transfusion volume during LTH. There were no differences in mortality or adverse outcomes according to patient sex., Conclusion: Patient sex and age may impact factors associated with LTH and therapies received. Studies in developmental hemostasis are needed to determine the optimal transfusion strategy for LTH according to patient sex and age., (© 2024 AABB.)

Background: Red blood cell (RBC) antibodies are common in multiply transfused patients with sickle cell disease (SCD). Unlike RBC alloantibodies, the potential of autoantibodies to cause post-transfusion hemolysis may be uncertain. Biotin-labeling provides a direct measurement of red cell survival (RCS) over time, thus can be used to assess the clinical significance of RBC antibodies. Antibodies to biotinylated RBC (B-RBC) occasionally are detected after exposure, which may impact B-RBC survival in subsequent RCS studies., Study Design and Methods: Pediatric patients with SCD receiving monthly chronic transfusions underwent RCS studies, receiving aliquots of allogeneic RBC labeled at distinct densities of biotin (2-18 μg/mL). B-RBC survival was followed for 4 months post-transfusion, and B-RBC antibody screening for 6 months. Patients with warm autoantibodies (WAA) or B-RBC antibodies are reported here., Results: RBC antibodies were detected during RCS in four patients: one with WAA, one with WAA followed by B-RBC-specific antibodies, and two with transient B-RBC antibodies within the first 5 weeks of exposure. B-RBC half-lives (T 50 ) ranged 37.6-61.7 days (mean 47.8 days). There was no evidence of increased hemolysis or accelerated B-RBC clearance in the presence of WAA or B-RBC antibodies., Discussion: Biotinylation of allogenic RBC can be used to assess the possible effects of RBC antibodies on transfusion survival in individual cases, particularly when it is uncertain if the detected antibodies may result in hemolysis. In the cases presented here, neither WAA nor B-RBC antibodies were associated with significant shortening of B-RBC survival in individuals with SCD., (© 2024 AABB.)

Purpose: Balanced blood product resuscitation with red blood cells, plasma, and platelets can be achieved using whole blood (WB) or component therapy (CT). However, balanced resuscitation of younger children with severe traumatic hemorrhage may be complicated by delays in delivering all blood components and concerns regarding multiple product exposures. We hypothesized that WB achieves balanced resuscitation faster than CT, with fewer product exposures and improved clinical outcomes., Methods: Children younger than 12 years receiving balanced resuscitation within 4 hours of arrival were identified from the 2017 to 2019 Trauma Quality Improvement Program database. Time to balanced resuscitation was defined as the time of initiation of WB or all three components. Patient characteristics, resuscitation details, and outcomes were compared between WB and CT groups. Time to balanced resuscitation was compared using Kaplan-Meier analysis and Cox regression modeling to adjust for covariates. Additional multivariable regression models compared number of transfusion exposures, intensive care unit (ICU) length of stay, and mortality., Results: There were 390 patients (109 WB, 281 CT) with median age 7 years, 12% penetrating mechanism, 42% severe traumatic brain injury, and 49% in-hospital mortality. Time to balanced resuscitation was shorter for WB versus CT (median, 28 vs. 87 minutes; hazard ratio [HR], 2.93; 95% confidence interval [CI], 2.31-3.72; p < 0.0001). Whole blood patients received fewer transfusion exposures (mean, 3.2 vs. 3.9; adjusted incidence rate ratio, 0.82; 95% CI, 0.72-0.92; p = 0.001) and lower total product volumes (50 vs. 85 mL/kg; p = 0.01). Intensive care unit stays trended shorter for WB versus CT (median, 10 vs. 12 days; adjusted HR, 1.32; 95% CI, 0.93-1.86), while in-hospital mortality was similar (50% vs. 45%; adjusted odds ratio, 1.11; 95% CI, 0.65-1.88)., Conclusion: In critically injured preadolescent children receiving emergent transfusion, WB was associated with faster time to balanced resuscitation, fewer transfusion exposures, lower blood product volumes, and a trend toward shorter ICU stays than CT., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)