Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis: A Secondary Analysis of a Randomized Clinical Trial.

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.

Reversibility of Cognitive Deficits and Functional Connectivity With Transfusion in Children With Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: People with sickle cell disease (SCD) are at risk of cognitive dysfunction independent of stroke. Diminished functional connectivity in select large-scale networks and white matter integrity reflect the neurologic consequences of SCD. Because chronic transfusion therapy is neuroprotective in preventing stroke and strengthening executive function abilities in people with SCD, we hypothesized that red blood cell (RBC) transfusion facilitates the acute reversal of disruptions in functional connectivity while white matter integrity remains unaffected. METHODS: Children with SCD receiving chronic transfusion therapy underwent a brain MRI measuring white matter integrity with diffusion tensor imaging and resting-state functional connectivity within 3 days before and after transfusion of RBCs. Cognitive assessments with the NIH Toolbox were acquired after transfusion and then immediately before the following transfusion cycle. RESULTS: Sixteen children with a median age of 12.5 years were included. Global assessments of functional connectivity using homotopy (p = 0.234) or modularity (p = 0.796) did not differ with transfusion. Functional connectivity within the frontoparietal network significantly strengthened after transfusion (median intranetwork Z-score 0.21 [0.17-0.30] before transfusion, 0.29 [0.20-0.36] after transfusion, p < 0.001), while there was not a significant change seen within the sensory motor, visual, auditory, default mode, dorsal attention, or cingulo-opercular networks. Corresponding to the change within the frontoparietal network, there was a significant improvement in executive function abilities after transfusion (median executive function composite score 87.7 [81.3-90.7] before transfusion, 90.3 [84.3-93.7] after transfusion, p = 0.021). Participants with stronger connectivity in the frontoparietal network before transfusion had a significantly greater improvement in the executive function composite score with transfusion (r = 0.565, 95% CI 0.020-0.851, p = 0.044). While functional connectivity and executive abilities strengthened with transfusion, there was not a significant change in white matter integrity as assessed by fractional anisotropy and mean diffusivity within 16 white matter tracts or globally with tract-based spatial statistics. DISCUSSION: Strengthening of functional connectivity with concomitant improvement in executive function abilities with transfusion suggests that functional connectivity MRI could be used as a biomarker for acutely reversible neurocognitive injury as novel therapeutics are developed for people with SCD.

Leading digit bias in hemoglobin thresholds for red cell transfusion.

BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Redefining hyperviscosity in acute leukemia: Potential implications for red cell transfusions in the microvasculature.

Hyperleukocytosis is an emergency of acute leukemia leading to blood hyperviscosity, potentially resulting in life-threatening microvascular obstruction, or leukostasis. Due to the high number of red cells in the circulation, hematocrit/hemoglobin levels (Hct/Hgb) are major drivers of blood viscosity, but how Hct/Hgb mediates hyperviscosity in acute leukemia remains unknown. In vivo hemorheological studies are difficult to conduct and interpret due to issues related to visualizing and manipulating the microvasculature. To that end, a multi-vessel microfluidic device recapitulating the size-scale and geometry of the microvasculature was designed to investigate how Hct/Hgb interacts with acute leukemia to induce "in vitro" leukostasis. Using patient samples and cell lines, the degree of leukostasis was different among leukemia immunophenotypes with respect to white blood cell (WBC) count and Hct/Hgb. Among lymphoid immunophenotypes, severe anemia is protective against in vitro leukostasis and Hct/Hgb thresholds became apparent above which in vitro leukostasis significantly increased, to a greater extent with B-cell acute lymphoblastic leukemia (ALL) versus T-cell ALL. In vitro leukostasis in acute myeloid leukemia was primarily driven by WBC with little interaction with Hct/Hgb. This sets the stage for prospective clinical studies assessing how red cell transfusion may affect leukostasis risk in immunophenotypically different acute leukemia patients.

Peripheral perfusion index stratifies risk in patients with intraoperative anemia: A multicentre cohort study.

STUDY OBJECTIVE: Evidence for red blood cell (RBC) transfusion thresholds in the intraoperative setting is limited, and current perioperative recommendations may not correspond with individual intraoperative physiological demands. Hemodynamics relevant for the decision to transfuse may include peripheral perfusion index (PPI). The objective of this prospective study was to assess the associations of PPI and hemoglobin levels with the risk of postoperative morbidity and mortality. DESIGN: Multicenter cohort study. SETTING: Bispebjerg and Hvidovre University Hospitals, Copenhagen, Denmark. PATIENTS: We included 741 patients who underwent acute high risk abdominal surgery or hip fracture surgery. INTERVENTIONS: No interventions were carried out. MEASUREMENTS: Principal values collected included measurements of peripheral perfusion index and hemoglobin values. METHODS: The study was conducted using prospectively obtained data on adults who underwent emergency high-risk surgery. Subjects were categorized into high vs. low subgroups stratified by pre-defined PPI levels (PPI: > 1.5 vs. < 1.5) and Hb levels (Hb: > 9.7 g/dL vs. < 9.7 g/dL). The study assessed mortality and severe postoperative complications within 90 days. MAIN RESULTS: We included 741 patients. 90-day mortality was 21% (n = 154), frequency of severe postoperative complications was 31% (n = 231). Patients with both low PPI and low Hb had the highest adjusted odds ratio for both 90-day severe postoperative complications (2.95, [1.62-5.45]) and 90-day mortality (3.13, [1.45-7.11]). A comparison of patients with low PPI and low Hb to those with high PPI and low Hb detected significantly higher 90-day mortality risk in the low PPI and low Hb group (OR 8.6, [1.57-162.10]). CONCLUSION: High PPI in acute surgical patients who also presents with anemia was associated with a significantly better outcome when compared with patients with both low PPI and anemia. PPI should therefore be further investigated as a potential parameter to guide intraoperative RBC transfusion therapy.

Association between perioperative red blood cell transfusions and postoperative venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Whether perioperative red blood cell transfusions increases the risk of postoperative venous thromboembolism is controversial and uncertain.We aims to explore the relationship between perioperative red blood cell transfusions and the risk of postoperative venous thromboembolism by conducting a meta-analysis. OBJECTIVE: To conduct a meta-analysis to systematically evaluate the relationship between perioperative red blood cell transfusions and the risk of postoperative venous thromboembolism. METHODS: PubMed, Embase, Cochrane, and Web of Science databases were searched to identify studies examining the relationship between perioperative red blood cell transfusions and the risk of postoperative venous thromboembolism. The databases were searched from establishment to August 2023.Two researchers independently screened literature and extracted data according to inclusion and exclusion criteria. Newcastle-ottawa Scale was used for quality assessment. Meta-analysis of data was performed using RevMan 5.4 software. RESULTS: A total of 15 studies involving 1,880,990 patients were included in this study.Meta-analysis showed that perioperative red blood cell transfusions increased the risk of postoperative venous thromboembolism [OR = 1.61, 95%CI (1.37, 1.89), P < 0.001]. Subgroup analyses showed that the transfusion dose,transfusion timing,study population and follow-up time were closely related to the risk of postoperative venous thromboembolism. CONCLUSIONS: In summary, this meta-analysis demonstrated a significant positive association between perioperative red blood cell transfusions and postoperative venous thromboembolism.Healthcare professionals should pay attention to the influence of blood transfusions on postoperative venous thromboembolism, strengthen management and prevention.

[PATIENT BLOOD MANAGEMENT - IT IS IMPOSSIBLE TO IGNORE THIS POLICY].

INTRODUCTION: Anemia is common and is an independent risk factor for morbidity and mortality, especially in pre- (30-40% of patients undergoing major surgery) or post-operative anemia (up to 80-90%). Using World Health Organization (WHO) criteria, in 2010 one quarter of the global population was anemic (1.9 billion people) and iron deficiency anemia (IDA( was and still remains the most common type of anemia worldwide, accounting for more than half of the total anemia burden. In a systematic analysis for the Global Burden of Disease Study 2016, IDA was the fourth leading cause of years lived with disability, particularly in women, thus highlighting prevention and treatment of IDA as a major public health goal. Red blood cells (RBC) transfusion is a common therapeutic intervention with considerable variation in clinical practice. More than 85 million units packed RBC (PRBC) are transfused annually worldwide. The principal indication for blood transfusion (BT) is anemia, yet a significant percentage of RBC transfusions are inappropriately overused. For many physicians and clinicians, across many different specialties, BT is still considered to be the first-line treatment when facing anemia. The Joint Commission along with the American Medical Association has included BT in a list of the five most overused therapeutic procedures in the United States. Restrictive blood transfusion (RBT) is an evidence-based policy, at least as effective, if not superior to the liberal policy of BT. Patient blood management (PBM) is a patient-centered systematic, evidence-based approach, supported by RBT. In this article we analyze the factors which influence the implementation of PBM.

Machine Learning-Based Prediction of Intraoperative Red Blood Cell Transfusion in Aortic Valve Replacement Surgery.

BACKGROUND: Blood shortage is a global challenge, impacting elective surgeries with high bleeding risk. Predicting intraoperative blood use, optimizing resource allocation, and ensuring safe elective surgery are vital. This study targets identifying key bleeding risk factors in Aortic Valve Replacement (AVR) through machine learning. METHODS: Data from 702 AVR patients were split into 70% training and 30% test sets. Thirteen models predicted RBC transfusion. SHapley Additive exPlanations (SHAP) analyzed risk factors. RESULTS: Logistic Regression excelled, with Area Under Curve (AUC) 0.872 and 81.0% accuracy on the test set. Notably, female gender, Hemoglobin (HGB) < 131.91 g/L, Hematocrit (HCT) < 0.41L/L, weight < 59.49 kg, age > 54.47 year, Mean Corpuscular Hemoglobin (MCH) < 29.15 pg, Total Protein (TP) > 69.7 g/L, FIB > 2.61 g/L, height < 160 cm, and type of operation is Surgical Aortic Valve Replacement (SAVR) were significant RBC transfusion predictors. CONCLUSIONS: The study's model accurately forecasts AVR-related RBC transfusions. This informs presurgery blood preparations, reducing resource waste and aiding clinicians in optimizing patient care.

Development of a Risk Assessment Model for Predicting Red Blood Cell Transfusion in Neonatal Patients.

BACKGROUND: The goal was to develop a risk assessment model for predicting red blood cell (RBC) transfusion in neonatal patients to assist hospital blood supply departments in providing small portions of RBCs to those requiring RBC transfusion on time. METHODS: Clinical information was collected from 1,201 children admitted to the neonatal unit. Clinical factors associated with predicting RBC transfusion were screened, and prediction models were developed using stepwise and multifactorial logistic regression analyses, followed by the evaluation of prediction models using receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). RESULTS: Overall, 81 neonatal patients were transfused with RBCs, and the variables of gestational age at birth, age < 1 month, receipt of mechanical ventilation, and infant anemia were included in the final prediction model. The area under the curve of the prediction model was 0.936 (0.921 - 0.949), which was significantly higher than that of the individual indicators of gestational age at birth, age at admission < 1 month, receipt of mechanical ventilation, and infant anemia (p < 0.001). DCA showed a standardized net benefit for the possible risk of infant RBC transfusion at 0.1 - 1.0. CONCLUSIONS: We developed a risk assessment model to predict the risk of RBC transfusion in neonatal patients that can effectively assess the risk of RBC transfusion in children.

Optimization of single-needle red cell exchange in patients with sickle cell disease.

The hypercoagulable state associated with sickle cell disease (SCD) can be challenging for apheresis procedures. Among 62 single-needle red cell exchanges (SN-RCEs) performed over a 15-month period, 4 patients experienced 6 hemolytic events with a discolored plasma layer, elevated plasma/RBC interface in the centrifuge, and accompanying alarms of "Cells were detected in plasma line from centrifuge" or "AIM system detected RBC at top of connector." The hemolysis originated from the apheresis instrument because samples from the apheresis belt but not the patients' peripheral blood were positive for hemolysis. Further analysis showed the alarms occurred more often in SN-RCEs (20.4%) than double-needle RCEs (2.7%), and the hemolysis was probably secondary to clumping. To optimize SN-RCE, we increased the anticoagulant dosage by changing Inlet/AC ratio from 13 to 8 and lowered the inlet rate to the level comparable to double-needle RCE. The adjustments were well-tolerated with no more hemolysis.

Does red blood cell transfusion affect clinical outcomes in critically ill patients? A report from a large teaching hospital in south Iran.

BACKGROUND: Despite the beneficial effects, RBC transfusion can be associated with infectious and non-infectious complications in critically ill patients. OBJECTIVES: Investigate current RBC transfusion practices and their effect on the clinical outcomes of patients in intensive care units (ICUs). DESIGN: Retrospective observational study. SETTING: Three mixed medical-surgical adult ICUs of a large academic tertiary hospital. PATIENTS AND METHODS: From March 2018 to February 2020, all adult patients admitted to medical or surgical ICU. Patients who received one or more RBC transfusions during the first month of ICU admission were included in the "transfusion" group, while the remaining patients were assigned to the "non-transfusion" group. MAIN OUTCOME MEASURES: Mortality and length of ICU and hospital stay. SAMPLE SIZE: 2159 patients. RESULTS: Of 594 patients who recieved transfusions, 27% of patients received red blood cell (RBC) products. The mean pre-transfusion hemoglobin (Hb) level was 8.05 (1.46) g/dL. There was a significant relationship between higher APACHE II scores and ICU mortality in patients with Hb levels of 7-9 g/dL (OR adjusted=1.05). Also, ICU mortality was associated with age (OR adjusted=1.03), APACHE II score (OR adjusted=1.08), and RBC transfusion (OR adjusted=2.01) in those whose Hb levels were >9 (g/dl). CONCLUSION: RBC transfusion was associated with an approximately doubled risk of ICU mortality in patients with Hb>9 g/dL. High APACHE II score and age increase the chance of death in the ICU by 8% and 3%, respectively. Hence, ICU physicians should consider a lower Hb threshold for RBC transfusion, and efforts must be made to optimize RBC transfusion practices. LIMITATIONS: Single-center and retrospective study.

Using Blood Wisely: lessons learnt in establishing a national implementation programme to reduce inappropriate red blood cell transfusion.

BACKGROUND: Up to 50% of blood is transfused inappropriately despite best evidence. In 2020, Choosing Wisely Canada launched a major national programme, 'Using Blood Wisely', the aim was to engage hospitals to audit their red blood cell transfusion use against national benchmarks and participate in a programme to decrease inappropriate use. STUDY DESIGN: Using Blood Wisely is a quality improvement programme including national benchmarks, an audit tool, recommended evidence-based effective interventions and a designation to reward success. Hospital engagement was measured using the number of hospitals signing up, performing a baseline audit, submitting the planning survey, entering two or more audits and achieving hospital designation. Barriers to implementation were collected. RESULTS: From 1 September 2020 to 31 December 2022, 229 individual hospitals signed up over time to participate. Their results are reported as 159 hospitals and hospital groups. Collectively, this accounts for 72% of the blood used in Canada. Overall, 147 (92%) performed a baseline audit, 10 (6%) submitted a planning survey and 130 (82%) entered two or more audits. At baseline (time of enrolment), 75 (51%) met both benchmarks. The designation was awarded to 62 (39%) hospital groups (a total of 105 individual hospitals) that met and sustained benchmarks. Barriers to implementation included human resource shortages, lack of local expertise to advise the team, need for more education of transfusion prescribers and competing priorities. CONCLUSION: In its initial phase, Using Blood Wisely engaged a substantial number of hospitals in transfusion quality improvement work and maintained that engagement. This large-scale engagement across a big country was more successful than anticipated. Additional efforts are needed to rigorously evaluate the programme's impact on utilisation.

Post-transfusion biotin-labeled red blood cell survival studies in pediatric sickle cell disease with antibodies of uncertain significance.

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 (T50) 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.

A novel measure to summarize blood transfusion practice during critical illness.

BACKGROUND: Large-scale observational studies have summarized transfusion practice using traditional measures of central tendency (e.g., the mean hemoglobin concentration at the time of transfusion). However, the mean hemoglobin concentration fails to identify specific hemoglobin concentration thresholds that drive practice. In the following brief report, we propose a novel measure of "practice discontinuity" that identifies specific practice-defining hemoglobin thresholds. STUDY DESIGN AND METHODS: We used the PINC AI Database (2016-2022) to identify adult patients admitted to an intensive care unit with at least one hemoglobin concentration measurement. For each day that hemoglobin was measured, we identified whether the patient received a red blood cell transfusion using hospital charge codes. We defined the "practice discontinuity" measure as the hemoglobin concentration at which there was the largest increase in transfusion use going from a higher to an incrementally lower hemoglobin concentration. We also calculated the mean and median pretransfusion hemoglobin concentrations. RESULTS: We identified 1,298,367 patients and 4,905,839 patient-days for inclusion. RBC transfusion occurred in a total of 530,654 (10.8%) patient-days. The overall pre-transfusion mean and median hemoglobin concentrations were 8.4 and 8.0 g/dL, respectively. The practice discontinuity measure identified 7.0 g/dL as the hemoglobin concentration at which transfusion use increased the most, from 46.6% of patient-days at a concentration of 7.0 g/dL to 74.8% of patient-days at a concentration of 6.9 g/dL. DISCUSSION: We propose that future studies of red blood cell transfusion practice consider inclusion of the practice discontinuity measure to more fully summarize clinical practice.

Rh immune globulin immunoprophylaxis after RhD-positive red cell exposure in RhD-negative patients via transfusion: A survey of practices.

BACKGROUND: Current Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD-negative patients are exposed to RhD-positive red cells. This is a survey of AABB-accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD-negative patients receive RhD-positive (i.e., RhD-incompatible) packed red blood cell (pRBC) and platelet transfusions. RESULTS: Approximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD-incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD-incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD-incompatible pRBC transfusions. DISCUSSION: With approximately half of US AABB-accredited institutions report having policies on RhIG immunoprophylaxis after both RhD-incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD-incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required. CONCLUSION: This survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh-negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

Luspatercept in low-risk myelodysplastic syndromes: a paradigm shift in treatment strategies.

INTRODUCTION: In patients with myelodysplastic syndromes (MDS), anemia is prevalent affecting 80%-85% of low-risk (LR-MDS) patients, with 40% eventually requiring red blood cell (RBC) transfusions. Except forlenalidomide, exclusively approved for those with deletion of chromosome 5q,erythropoiesis-stimulating agents (ESAs) are the primary treatment choice for low-risk patients. Those unresponsive to ESAs face limited alternatives, eventually necessitating long-term RBC transfusions, leading to secondary iron overload and adversely affecting quality of life (QoL). AREA COVERED: Luspatercept is a pioneering erythroid maturation agent. It received approval by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for treating adults experiencing transfusion-dependent anemia associated with LR-MDS or ß-thalassemia. Recently, the FDA approved luspatercept as first- line therapy in patients with very low- to intermediate-risk MDS who require RBC transfusions and have not previously received ESAs. This review summarizes the historical impact of luspatercept intreating LR-MDS unresponsive to ESAs and illustrates its potential benefit asfrontline therapy in MDS and its employment in patients with myelofibrosis-induced anemia. EXPERT OPINION: Luspatercept has revolutionized the therapeutic paradigm of LR-MDS, for which there was a limited therapeutic arsenal, especially in the setting of patients who did not respond or fail after ESA treatment.

Increased platelet to red blood cell transfusion ratio associated with acute kidney injury in children with life-threatening bleeding.

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.

Red blood cell transfusion in neurocritical patients: a systematic review and meta-analysis.

BACKGROUND: Anemia can lead to secondary brain damage by reducing arterial oxygen content and brain oxygen supply. Patients with acute brain injury have impaired self-regulation. Brain hypoxia may also occur even in mild anemia. Red blood cell (RBC) transfusion is associated with increased postoperative complications, poor neurological recovery, and mortality in critically ill neurologic patients. Balancing the risks of anemia and red blood cell transfusion-associated adverse effects is challenging in neurocritical settings. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE (PubMed) from inception to January 31, 2024. We included all randomized controlled trials (RCTs) assessing liberal versus restrictive RBC transfusion strategies in neurocritical patients. We included all relevant studies published in English. The primary outcome was mortality at intensive care unit (ICU), discharge, and six months. RESULTS: Of 5195 records retrieved, 84 full-text articles were reviewed, and five eligible studies were included. There was no significant difference between the restrictive and liberal transfusion groups in ICU mortality (RR: 2.53, 95% CI: 0.53 to 12.13), in-hospital mortality (RR: 2.34, 95% CI: 0.50 to 11.00), mortality at six months (RR: 1.42, 95% CI: 0.42 to 4.78) and long-term mortality (RR: 1.22, 95% CI: 0.64 to 2.33). The occurrence of neurological adverse events and most major non-neurological complications was similar in the two groups. The incidence of deep venous thrombosis was lower in the restrictive strategy group (RR: 0.41, 95% CI: 0.18 to 0.91). CONCLUSIONS: Due to the small sample size of current studies, the evidence is insufficiently robust to confirm definitive conclusions for neurocritical patients. Therefore, further investigation is encouraged to define appropriate RBC transfusion thresholds in the neurocritical setting.