Packed Red Blood Cell Transfusion Research Articles

Sustained Efficacy, Safety, and Improved Quality of Life in Adult and Pediatric Patients with Transfusion-Dependent β-Thalassemia up to 9 Years Post Treatment with Betibeglogene Autotemcel (Beti-cel)

Introduction: Beti-cel gene therapy addresses the underlying cause of transfusion-dependent β-thalassemia (TDT) by adding functional copies of a modified β-globin gene to autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) via a third-generation, self-inactivating lentiviral vector (LVV), BB305, which produces functional adult hemoglobin (Hb), HbA T87Q, in red blood cells (RBCs). Here, we report efficacy, safety, and quality of life (QOL) data from adult and pediatric patients treated with beti-cel who were followed for up to 9 years after treatment. These outcomes may inform patient selection for real-world treatment with beti-cel. Methods: Patients with TDT who completed either a phase 1/2 (HGB-204 [NCT01745120]; HGB-205 [NCT02151526]) or phase 3 (HGB-207 [NCT02906202]; HGB-212 [NCT03207009]) beti-cel parent study and subsequently participated in the long-term, 13-year follow-up study LTF-303 (NCT02633943) were included in this analysis. Analyses were performed with data collected through January 30, 2023. Efficacy (including transfusion independence [TI], defined as a weighted average Hb ≥9 g/dL without packed RBC transfusions for ≥12 months) and safety are reported through last follow-up. QOL data are reported for studies HGB-204, HGB-207, and HGB-212 through month 36. Statistical analyses were conducted to examine key outcomes in subgroups based on patient age at enrollment (pediatric: <18 years; adult: ≥18 years). Results:As of January 30, 2023, 63 patients (median [range] age: 17 [4-35] years) had received beti-cel in a phase 1/2 or 3 study and enrolled in LTF-303, with a median (range) follow-up of 60.1 (23.8-109.5) months. Phase 3 studies used the commercial drug product manufacturing process. Ninety percent (37/41) of phase 3 patients achieved and maintained TI through last follow-up (up to 6 years; Table 1). TI rates by study, genotype, and age for phase 3 patients are also presented in Table 1. In phase 1/2 studies that used an older drug manufacturing process, 68.2% (15/22) of patients achieved TI; 14 of these patients sustained TI through last follow-up (up to 9 years). One patient no longer meets protocol-defined TI as a result of Hb level <9g/dL at year 6 due to acute health events unrelated to β-thalassemia, which were not attributed to loss of beti-cel treatment effect. Approximately 80% of pediatric and adult patients required only one mobilization cycle to achieve the drug product dose. The median percentage of drug product cells transduced with the BB305 LVV was comparable between adult and pediatric populations (78% and 80%, respectively), as were the month 6 median peripheral blood vector copy number (1.4 c/dg and 1.1 c/dg) and HbA T87Q (9.4 g/dL and 8.3 g/dL). Adult patients reported improvements in QOL up to month 36 as assessed by the Short Form-36 Health Survey Questionnaire mental and physical component summary scores, Functional Assessment of Cancer Therapy, and EuroQol ( Table 2). Pediatric Quality of Life Inventory scores will be reported at the time of presentation. Overall, 19% (12/63) of patients experienced ≥1 beti-cel-related adverse event (AE); the most common beti-cel-related AEs (occurring in ≥3 patients) were abdominal pain (experienced in 5/63 [7.9%] patients) and thrombocytopenia (3/63 [4.8%] patients). Five patients experienced serious veno-occlusive liver disease; all 5 received defibrotide and recovered. No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported. Age subgroup safety analysis as of last follow-up will be reported in the final presentation. Conclusion: Beti-cel is a potentially curative gene therapy for patients with TDT across ages and genotypes through achievement of TI and normal or near-normal Hb. These data will inform real-world beti-cel treatment decisions for patients with TDT and providers.

AsCas12a Gene Editing of HBG1/2 Promoters with EDIT-301 Results in Rapid and Sustained Normalization of Hemoglobin and Increased Fetal Hemoglobin in Patients with Severe Sickle Cell Disease and Transfusion-Dependent Beta-Thalassemia

Background: Sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) are hereditary blood disorders caused by mutations in the β-globin gene. Clinical evidence has demonstrated that increased fetal hemoglobin (HbF, α2γ2) can reduce or eliminate SCD and TDT complications. EDIT-301, an investigational gene-edited autologous hematopoietic stem cell medicine, has a unique genomic modification that mimics naturally occurring mutations of hereditary persistence of fetal hemoglobin in the γ-globin gene ( HBG1/2) promoters. These mutations reactivate γ-globin expression and increase HbF production. EDIT-301 is manufactured with a highly efficient and specific, proprietary gene editing nuclease, AsCas12a. In preclinical studies, edited CD34 + cells from patients with SCD or TDT increased HbF production in red blood cells (RBCs) sufficient for a therapeutic effect, including reduced sickling (SCD) and improved erythropoiesis (TDT). Aim: RUBY (NCT04853576) and EdiThal (NCT05444894) are Phase I/II, multicenter, open-label, single-arm studies evaluating the safety, efficacy, and tolerability of EDIT-301 in patients with severe SCD and TDT, respectively. As of June 28, 2023, 7 SCD patients and 2 TDT patients have received EDIT-301 treatment. Preliminary clinical efficacy and safety data are reported. Methods: Patients aged 18-50 years with severe SCD (defined as ≥2 severe vaso-occlusive events [VOEs] per year in the 2 years prior to informed consent [IC]) and patients aged 18-35 years with TDT (defined as at least 100 mL/kg/year or 10 U/year of packed RBC transfusions in the 2 years prior to IC) were eligible to enroll in RUBY and EdiThal, respectively. Autologous CD34 + hematopoietic stem and progenitor cells collected by apheresis after plerixafor (RUBY) or plerixafor + filgrastim (EdiThal) mobilization were edited at the HBG1/2 promoters with AsCas12a. After myeloablative conditioning with busulfan, patients received a single infusion of EDIT-301 (a minimum of 3 × 10 6 CD34 + cells/kg), and were monitored for engraftment, total hemoglobin (Hb), HbF, mean HbF concentration/F-cell (MCH-F/F-cell), percentage of F-cells, markers of hemolysis, transfusion requirement, VOEs (SCD only), and adverse events (AEs) for 24 months. Results: Based on a data cut of June 28, 2023, Patients 1-4 with SCD were 12-, 9-, 4-, and 4-months post-EDIT-301 infusion, respectively. Patients 5-7 with SCD were <1-month post-EDIT-301 infusion. Patients 1-2 with TDT were 3- and <1-months post-EDIT-301 infusion, respectively. Neutrophil and platelet engraftment were achieved after a mean (range) of 25 (23-29) and 27 (19-37) days in Patients 1-4 with SCD and on Day 23 and 26 in Patient 1 with TDT, respectively. There were no VOEs in SCD patients post-EDIT-301 infusion, compared with a mean (range) of 4.2 (3.0-5.5) VOEs/year in the 2 years before enrollment (n=6). Following EDIT-301 infusion, Hb levels rapidly increased to 14.2 (12.4-15.7) g/dL by Month 4 (n=4), reaching the normal physiological range, from a mean (range) of 10.5 (8.5-11.9) g/dL at baseline (n=5). By Month 4, the mean (range) HbF concentration was 6.8 (5.7-7.6) g/dL and HbF was >40% (n=4); Patients 3 and 4 had >50% HbF. Percentage of F-cells and MCH-F/F-cell also increased. Key markers of hemolysis improved or normalized in all patients with SCD. Patient 1 with TDT had a HbF concentration of 7.2 g/dL by Month 3, stopped receiving RBC transfusions 20 days after EDIT-301 infusion, and remained transfusion free through the 3-month period. Patient 2 with TDT also showed early improvements. The safety profile of EDIT-301 in both SCD and TDT was consistent with myeloablative conditioning with busulfan. No serious AEs were reported after EDIT-301 infusion. Conclusion: These data demonstrated successful engraftment, a rapid and sustained normalization of Hb as early as 4 months after infusion, an increase in HbF and percentage of F-cells, resolution of VOEs (SCD) and transfusion independence (TDT). In addition, there were improvements in key markers of hemolysis (SCD) and a favorable safety profile in EDIT-301-treated patients. EDIT-301 treatment showed promising results for the first clinical use of AsCas12a in both SCD and TDT patients after gene editing of the γ-globin gene ( HBG1/2) promoters. These findings support further investigation of EDIT-301 in the RUBY and EdiThal trials. Updated data with additional outcomes will be presented.

Improvements in Health-Related Quality of Life after Exagamglogene Autotemcel in Patients with Transfusion-Dependent Beta-Thalassemia

Background: Transfusion-dependent β-thalassemia (TDT), an inherited hematological disorder which requires life-long, chronic red blood cell transfusion (RBC) and regular iron chelation therapy, has a substantial negative impact on health-related qualify of life (HRQoL). Exagamglogene autotemcel (exa-cel) is a one-time, non-viral, ex vivo CRISPR-Cas9 gene-edited cell therapy in phase 3 clinical trials that has been shown to eliminate the need for RBC transfusions and achieve transfusion independence. Here, we report HRQoL data from a pre-specified interim analysis of the exa-cel CLIMB TDT-111 study. Methods: CLIMB TDT-111 is an ongoing, 24-mo, phase 3 trial of a single dose of exa-cel in patients aged 12-35 years with TDT and a history of ≥100 mL/kg/year or ≥10 U/year of packed RBC transfusions for 2 years prior to screening. Changes in patient-reported outcome (PRO) measures including EuroQol Quality of Life Scale 5 dimensions 5 levels of severity (EQ-5D-5L, including descriptive system and visual analog scale [VAS]) and Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, including FACT-General [FACT-G] and bone marrow transplant subscale [BMTS]) for adults and the EuroQol Quality of Life Scale 5 dimensions youth (EQ-5D-Y) and Pediatric Quality of Life Inventory (PedsQL) for adolescents were assessed through month 24 as a secondary endpoint in the trial. Data are presented as of 16 January 2023 for the 24 adults (aged ≥18-35 years) and 11 adolescents (aged ≥12 to < 18 years) who had been followed for ≥16 months after exa-cel infusion. Results: Clinically meaningful improvements, exceeding the minimal clinically important difference (MCID) thresholds, were observed in all PRO measures in adults. Baseline mean EQ-5D-5L health utility US index score (n=24, mean [SD]: 0.85 [0.18]) was near the general population norm and in line with baseline scores previously reported for adult patients with TDT. By month 24, both EQ-5D-5L health utility US index scores and EQ VAS scores showed substantial improvement (mean [SD] changes at month 24 [n=15]: 0.12 [0.26] and 10.2 [20.9] points; MCIDs 0.078 and 7 to 10, respectively). FACT-G Total Score improved from baseline by month 12 and was sustained through month 24 (mean [SD] change at month 24 [n=15] 10.3 [17.0] points; MCID 3 to 7), with improvements observed in all 4 subscales (physical, social/family, emotional, and functional well-being). BMTS score improved by month 12 and was sustained through month 24 (mean [SD] change at month 24 [n=15] 6.8 [4.7] points; MCID 2 to 3). For adolescents, EQ VAS scores improved through month 18 (mean [SD] change from baseline 4.8 [6.1] points). Total PedsQL score improved by month 6 and was sustained through month 18 (mean [SD] change from baseline [n=7] 14.1 [9.2] points; MCID 4.36). Physical functioning and psychosocial health scores, sub-components of PedsQL, both showed sustained improvement through month 18 (mean [SD] change [n=7] 19.2 [9.1] and 11.4 [10.9] points; MCID of 6.66 and 5.30 points, respectively). Improvement in psychosocial score was observed in all 3 subscales (social, emotional, and school functioning). Conclusion: Adults and adolescents infused with exa-cel reported sustained and clinically meaningful improvements in their HRQoL, with improvements observed across different instruments and domains, including physical, emotional, social/family and functional well-being and overall health status. These results demonstrate the broad clinical benefits of exa-cel in patients with TDT.

The impact of red blood cell transfusion in preterm neonates on germinal matrix hemorrhage: incidence and grade with correlation to outcome

BackgroundGerminal matrix hemorrhage affects 20 to 25% of infants with a low birth weight (less than 1500 g). About one-tenth of them progress to intra-parenchymal hemorrhage, usually during the first days after birth. Several studies have found a correlation between packed RBC transfusions and a higher frequency of severe germinal matrix hemorrhage in neonatal intensive care units.Transcranial ultrasound is a safe, noninvasive modality that can be used repeatedly in the neonates with ability to detect different grades of germinal matrix hemorrhage.ObjectiveWas to evaluate the impact of packed RBC transfusion on the incidence and grade of germinal matrix hemorrhage, as evaluated by transcranial Doppler, and correlation to outcome.MethodsThis prospective observational study included one hundred preterm infants admitted to NICU, suffering from GM hemorrhage throughout 9 months duration. Bedside transcranial ultrasound was done for all the patients with a correlation of the grade of hemorrhage to the onset of blood transfusion, different clinical parameters, and the outcome.ResultsStatistical analysis showed a significant relation between the age of the first PRBC transfusion and GM hemorrhage grade. A positive relation was found between total amounts of PRBC transfusion and increasing grade of GM hemorrhage. A negative relation was found between GM hge grades and Apgar scores. GM hge patients who received PRBC transfusion had lower mean birth weight, lower gestational age, and longer duration of hospital stay than those who have not received PRBC transfusion.ConclusionClose monitoring of preterm neonates receiving packed RBCs, by transcranial ultrasound, as early as possible, is mandatory to early detect GM hge and limit subsequent morbidities.

Unraveling Leukocyte Profile Shifts and Platelet Dynamics Following Leukoreduced Packed Red Cell Transfusions in Very Low Birth Weight Preterm Neonates.

Background Packed red blood cell (PRBC) transfusions are routine in neonatal care and the most common blood product administered to sick neonates. However, their impact on leukocyte and platelet profiles in very low birth weight (VLBW) preterm infants remains largely unexplored.This study examines leukocyte profile shifts and platelet dynamics following leukoreduced PRBC transfusions in VLBW preterm infants, offering insights to improve neonatal care and reduce unnecessary interventions. Methods The study utilized a retrospective cohort design within a single center, focusing on VLBW preterm infants who received PRBC transfusions at a level 3 NICU between January 2014 and June 2019. Data collection encompassed white blood cell (WBC) and platelet count measurements taken 24 hours before and up to 72 hours after PRBC transfusion. Neonates lacking complete blood count (CBC) data within the 72-hour post-transfusion window were excluded. A subgroup analysis distinguished the outcome between the initial PRBC transfusion and subsequent ones. The statistical significance of pre- and post-transfusion laboratory data was determined using the Wilcoxon signed ranks test and paired T-test. Results A cohort of 108 VLBW preterm infants who underwent a total of 402 PRBC transfusions was included in the analysis. The subjects exhibited a mean gestational age of 27.2 ± 2.5 weeks and a mean birth weight of 913 ± 264 grams. Analysis of pre- and post-transfusion data revealed no significant differences in total white blood cell count (WBC), absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute eosinophil count, and absolute lymphocyte count. Notably, the platelet count was significantly decreased in the post-transfusion group (p < 0.001). In a subset analysis limited to the first-time transfusions among the 108 infants, a statistically significant increase was observed in total WBC, AMC, and ANC following transfusion. Conclusions The findings of this study highlight that PRBC transfusions can prompt an increase in neutrophils, monocytes, and eosinophils, coupled with a decline in platelet counts, all within a 72-hour window post-transfusion. Notably, these changes were predominantly discernible after the initial transfusion, with subsequent transfusions demonstrating consistency, except for the observed platelet count reduction. Recognizing these patterns could prove instrumental in averting undue investigations for suspected sepsis, particularly following the initial transfusion event. However, further in-depth investigations are necessary to uncover the underlying factors responsible for the shifts in leukocyte and platelet profiles triggered by PRBC transfusions.

Real-World Presentation and Prognostic Effect of Allogeneic Blood Transfusion during the Intensive Induction Phase in Pediatric Acute Lymphoblastic Leukemia.

Purpose: To determine associations between allogeneic blood transfusion (ABT) during the intensive induction phase of therapy and prognostic effect in a real-world cohort of pediatric patients with acute lymphoblastic leukemia (ALL). Methods: A total of 749 pediatric patients who were diagnosed with ALL were enrolled in this study by using a single-center retrospective cohort study method from February 2008 to May 2022. Results: Among the ABT patients, 711 (94.9%) children were transfused with packed red blood cells (PRBCs), 434 (57.9%) with single-donor platelets (SDPs), and 196 (26.2%) with fresh frozen plasma (FFP). Our multivariate analysis demonstrated that FFP transfusion was the unique independent factor that affected both relapse-free survival (RFS) and overall survival (OS). The transfusion of FFP was significantly associated with higher age (p < 0.001), being more likely to receive SCCLG-ALL-2016 protocol (p < 0.001), higher proportion of more than 25 blood product transfusions, more PRBC transfusion (p < 0.001), and higher D33-MRD-positive rates (p = 0.013). Generalized additive models and threshold effect analysis using piece-wise linear regression were applied to identify the cut-off value of 25 mL/kg for average FFP transfusion. K-M survival analysis further confirmed that average FFP transfusion > 25 mL/kg was an independent adverse indicator of inferior outcome in terms of RFS (p = 0.027) and OS (p = 0.033). Conclusions: In blood products, only FFP supplement is closely related to the prognosis of childhood ALL. During the intensive induction phase, the indications of FFP transfusion should be strictly grasped, and the total amount of FFP should be controlled and kept below 25 mL/kg.

Efficacy of the Hepcon system in reducing hemorrhagic and thrombotic complications in antiphospholipid syndrome patients undergoing cardiac surgery.

Patients with Antiphospholipid Syndrome (APS) undergoing cardiopulmonary bypass (CPB) surgery are at increased risk for thrombotic and hemorrhagic complications. Anticoagulation during CPB is typically monitored with activated clotting time (ACT) which may be falsely prolonged in patients with APS. The Hepcon Hemostasis Management System quantitatively determines the whole blood heparin concentration through heparin/protamine titration. This was a retrospective study of APS patients who underwent cardiac surgery requiring CPB at the Cleveland Clinic between April 2013, and July 2020. The primary endpoint was the composite rate of hemorrhagic or thromboembolic complications per surgical case in patients monitored by Hepcon versus patients monitored by ACT. Secondary endpoints were median volume of chest tube output and packed red blood cell (PRBC) transfusion within the first three post-operative days. 43 patients were included. 20 (47%) patients were monitored using Hepcon while 23 (53%) were monitored using ACT. For the primary endpoint of rate of thromboembolic or hemorrhagic complications per surgical case, there was no statistically significant difference between the Hepcon and ACT groups (HMS, 6/20 [30%]; ACT, 7/23 [30%]; p = >0.99). For the secondary endpoints, there was no statistically significant difference in median post-operative chest tube output (780mL vs. 850mL; p = 0.88) and median post-operative PRBC transfusion (1 unit vs. 0 unit; p = 0.28) between the Hepcon and ACT groups, respectively. There was no difference in the composite outcome of thrombotic or hemorrhagic complications in patients monitored by Hepcon versus those monitored by ACT.

In hospitalized patients undergoing therapeutic plasma exchange, major bleeding prevalence depends on the bleeding definition: An analysis of The Recipient Epidemiology and Donor Evaluation Study-III.

Major bleeding in patients undergoing therapeutic plasma exchange (TPE) has been studied in large databases; but without standardizing bleeding definitions. Therefore, we used standardized definitions to evaluate major bleeding in hospitalized patients undergoing TPE using public use data files from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). In a retrospective cross-sectional analysis, we identified TPE-treated adults in a first inpatient encounter. We evaluated major bleeding prevalence using (1) International Classification of Diseases (ICD) or Current Procedural Terminology (CPT) codes, (2) packed red blood cell (PRBC) transfusion, or (3) hemoglobin (Hgb) decline. Patients with major bleeding prior to their first TPE were excluded from the analysis. Among 779 patients undergoing TPE, major bleeding by at least one of the three bleeding definitions occurred in 135 patients (17.3%). For each of the ICD/CPT, PRBC, and Hgb definitions, the prevalence of major bleeding was 2.8% (n = 31), 7.4% (n = 81), and 5.4% (n = 59), respectively. Only 3.7% of bleeds (5/135) were captured by all three definitions and 19.3% (26/135) exclusively by any two pairwise definitions. The addition of PRBC transfusion and Hgb decline to ICD/CPT code definitions increased bleeding prevalence threefold. Among hospitalized adults undergoing TPE in the REDS-III study, the prevalence of major bleeding was 17.3%. The addition of PRBC and Hgb decline to ICD codes increased bleeding prevalence threefold. Future studies are needed to develop validated models that identify patients at risk for major bleeding during TPE.

Red cell transfusions in children with thalassemia: Outcomes of a10mL/kg/h infusion rate.

Children with transfusion-dependent thalassemia have an impaired ability to synthesize alpha or beta globin, which results in anemia. Packed red blood cell (PRBC) transfusions are required to increase hemoglobin, which supports appropriate growth and development. PRBC transfusions must be completed within 4h; however, infusion rates vary across institutions. Our institution infuses PRBCs up to 10mL/kg/h. A descriptive study of 21 children who received a total of 276 transfusions during 2021 demonstrated that this rate is safe and well tolerated. Shorter transfusion times support patients' and families' time, resources, and quality of life and aptly utilize institutional resources.

Age and sex differences in blood product transfusions and mortality in trauma patients at a level I trauma center

ObjectivesHemorrhage is a common complication of trauma. We evaluated age and sex differences in treatment with blood product transfusions and massive transfusions as well as in-hospital mortality following trauma at a Level 1 Trauma Center. MethodsThis cross-sectional study evaluated trauma data from a Level 1 trauma center registry from January 2013 to December 2017. The primary outcome was amount of blood products (packed red blood cells (PRBCs), plasma, platelets), and massive transfusion (MT) by biological sex and by age group: 16-24 (youth), 25-59 (middle age), and >=60 (older age) The secondary outcome was in-hospital mortality to hospital discharge. ResultsThere were 13596 trauma patients in the registry, mean age was 48 years, 4589 (34%) female and 9007 (66%) male, and median ISS of 9. Male patients received significantly more PRBC transfusions than female patients within 4-hours 6.6% vs 4.4%, and 24-hours 6.7% vs 4.5% respectively. Older patients received significantly fewer PRBC transfusions within 4-hours and 24-hours than their younger counterparts, with 6.9% in the youth group, 6.8% in the middle age group, and 3.9% in the older group (p<0.001). When adjusted for injury severity, the odds of receiving a blood transfusion within 4 hours of injury was significantly lower in older females. Using multivariate analysis, predictors of mortality included (in order of significance) injury severity, older age, transfusion within 4 hours of injury, penetrating trauma, and male sex. ConclusionIn this large trauma cohort, older female trauma patients were less likely to receive blood products compared to younger females and to their older male counterparts, even after adjusting for injury severity. Predictors of mortality included injury severity, older age, early transfusion, penetrating trauma, and male sex. Following trauma, older women appear vulnerable to undertreatment. Further study is needed to determine the reasons for these differences and their impact on patient outcomes.

Risk Factors and Management of Blunt Inferior Vena Cava Injury: A Retrospective Study.

Traumatic inferior vena cava (IVC) injuries are uncommon, but the mortality rate remains high at 38-70%. To date, most studies on traumatic IVC injuries have evaluated blunt rather than penetrating injuries. We aimed to identify the clinical features and risk factors that affect the prognosis of patients with blunt IVC injuries to improve treatment strategies for these patients. We retrospectively analyzed patients diagnosed with blunt IVC injury over 8years at a single trauma center. Clinical and biochemical parameters; transfusion, surgical, and resuscitation methods; associated injuries; intensive care unit stay; and complications data were compared between survival and death groups to identify clinical features and risk factors of blunt IVC injury-related mortality. Twenty-eight patients with blunt IVC injury were included during the study periods. Twenty-five (89%) patients underwent surgical treatment, and the mortality was 54%. The mortality rate according to the IVC injury location was the lowest for supra-hepatic IVC injury (25%, n = 2/8), whereas it was the highest for retrohepatic IVC injury (80%, n = 4/5). In the logistic regression analysis, Glasgow Coma Scale (GCS) (odds ratio [OR] = 0.566, 95% confidence interval [CI] [0.322-0.993], p = 0.047) and red blood cell (RBC) transfusion for 24h (OR = 1.132, 95% CI [0.996-1.287], p = 0.058) were independent predictors for mortality. Low GCS score and high-volume packed RBC transfusion requirements for 24h were significant predictors of mortality in patients with blunt IVC injuries. Unlike IVC injuries caused by penetrating trauma, supra-hepatic IVC injuries caused by blunt trauma have a good prognosis.

Case Comparison of Preterm Infant Stability During Packed Red Blood Cell Transfusions.

Very preterm infants (less than 32 weeks gestational age) experience acute morbidity during their stay in a neonatal intensive care unit. Because of their prematurity and frequent laboratory testing, they experience anemia, requiring correction with packed red blood cell (PRBC) transfusion(s). PRBC transfusions have been linked to neonatal morbidity, such as necrotizing enterocolitis, but never signs and symptoms of physiological stability. The secondary data analysis aimed to examine very preterm infants' physiological stability before, during, and after PRBC transfusions. A within-case, mixed-methods design was used in a secondary data analysis for 16 transfusion cases from 13 very preterm infants. The findings showed very preterm infants with physiological variables falling within defined limits based on gestational age during the transfusion. Two contrasting case exemplars will be presented. PRBC transfusions are necessary and prevent morbidity in very preterm infants. Observing instability during transfusions and prospectively studying hypothermia, cardiac instability, and thermal gradients is essential to design interventions to decrease morbidity associated with PRBC transfusions.

Alloimmunization in children with sickle cell disease: A tertiary care experience

IntroductionPatients with sickle cell disease (SCD) show a high prevalence of red blood cell (RBC) alloimmunization, however, few studies have focused on children. The present study was undertaken to determine the prevalence of alloimmunization and autoimmunity in children with SCD and to assess any correlation with age, number of transfusions received, and the number and frequency of crisis. Material & methodsSixty children affected with homozygous SCD, aged between five to eighteen years and having received more than one packed red blood cell (PRBC) transfusion were enrolled in the study.The preliminary tests included antiglobulin test (indirect and direct), alloantibody screening by three panel, antibody typing using 11 panel and auto-control test to detect autoantibodies. ResultsDirect antiglobulin test was negative in all the 60 patients, whereas indirect antiglobulin test was positive in 4/60 (6.6%) patients. Specific typing of alloantibodies revealed anti-D and anti-Kell antibodies in 2 (3.3%) each. Patients with alloantibody (4) had a higher mean age at onset of first symptom (7.05 ± 2.12 years) and age at first transfusion (7.5 ± 2.12 years) as compared to those without alloantibody, (4.48 ± 3.09 and 4.91 ± 3.12 years respectively). Patients with alloantibody received more PRBC transfusions, maintained low hemoglobin, required higher doses of hydroxyurea and also had a larger liver and spleen. ConclusionThe present study found a low prevalence of antibodies in patients with SCD. Patients presenting with symptoms of SCD at younger age received hydroxyurea at an earlier age. Starting hydroxyurea at an earlier age may decrease subsequent alloantibodies development. Larger studies to compare groups of patients related to administration of hydroxyurea are required to confirm this hypothesis.

Cardiac iron overload in pediatric oncology and bone marrow transplant survivors.

e22022 Background: Cardiovascular late effects are a leading cause of mortality and morbidity in childhood cancer and Bone Marrow Transplant (BMT) survivors. In patients receiving chronic red blood cell transfusions, excess iron may be deposited in the liver, heart, and pituitary gland. Iron overload cardiomyopathy is characterized as a restrictive physiology with early diastolic dysfunction ultimately progressing to end-stage dilated cardiomyopathy. Iron loading in the heart can also lead to arrhythmias and increase myocardial ischemia reperfusion injury due to increased formation of reactive oxygen species. It is not yet known whether high transfused packed red blood cell (PRBC) volumes in cancer and BMT patients leads to cardiac iron deposition, and whether iron-induced cardiac injury contributes to the known cardiovascular late effects in these patients. Methods: 83 childhood cancer and BMT survivors with elevated serum ferritin levels and subsequent liver Magnetic Resonance (MR) imaging were identified. 18 patients (21.7%) who had liver iron content of &gt; 12mg/g (mean 16.0 ± 7.36 mg/g) also underwent Cardiac MRI (CMR) to determine cardiac iron content. Results: Median transfused blood volume was 393 ml/kg [95% Confidence Interval (CI) 170-780 ml/kg]. All 18 patients had at least one echocardiogram showing normal ventricular ejection fractions [mean 65.1 ± Standard Deviation (SD) 3.53%] and normal shortening fractions (mean 35.4 ± 3.67%). All patients had myocardial iron content within normal ranges (T2* relaxation time mean 35.1 msec ± 7.1 [normal &gt;20 msec], mean ± SD iron content 0.63± 0.2 mg/g dry weight, range 0.5-1.1). There was no association of cardiac iron content with transfused blood volume, anthracycline dose (mg/m2) or liver iron content (Pearson Correlation Coefficients 0.27, 0.29 and 0.89 respectively). Conclusions: Childhood cancer and BMT patients receive multiple PRBC transfusions to treat symptomatic anemia. It is currently unknown whether excess iron deposition in the heart contributes to the cardiac effects of impaired diastolic function and ultimately systolic dysfunction. In this study, 11 of 18 patients (61.1%) with high levels of liver iron had at least 1 other risk factor for the development of future cardiac dysfunction (either anthracycline exposure, radiation to the chest or total body irradiation or both). Larger studies are needed to determine whether oncology patients with high levels of iron deposition in their liver are also at risk for clinically significant cardiac iron loading, and what risk factors may exist for elevated myocardial iron content.

Predictors of Mortality in Trauma patients Receiving massive Transfusion Protocol.

Massive transfusion protocol (MTP) is often defined as the transfusion of ≥10 units of packed red blood cells (PRBCs) in 24hours. The purpose of this study is to determine which factors most significantly contribute to mortality in patients receiving MTP after trauma. An initial database search followed by retrospective chart review was performed on patients treated at four trauma centers in Southern California. Data were collected on all patients who received MTP, defined as at least 10 units PRBCs within the first 24hours of admission, between January 2015 and December 2019. Patients with isolated head injuries were excluded. Univariate and multivariate analyses were used to determine which factors most significantly influenced mortality. Of 1278 patients who met our inclusion criteria in the database, 596 (46.6%) survived and 682 (53.4%) died. On univariate analysis initial vitals and labs, except for initial hemoglobin and initial platelet count were significant predictors of mortality. A multivariate regression model showed the strongest predictors of mortality were pRBC transfusions at 4 hours (OR 1.073, CI 1.020-1.128, P = .006) and 24hours (OR 1.045, CI 1.003-1.088, P = .036), and FFP transfusion at 24hours (OR 1.049, CI 1.016-1.084, P = .003). Our data indicates that several factors may contribute to mortality in patients receiving MTP. In particular age, mechanism, initial GCS, and PRBC transfusions at 4 and 24hours provided the strongest correlation. Further multicenter trials are indicated to provide further guidance in deciding when to discontinue massive transfusion.

Iron Deficiency Anemia and Ischemic Stroke in Premenopausal Women (P14-5.022)

<h3>Objective:</h3> We describe three young women with iron deficiency anemia who developed ischemic strokes in the absence of typical risk factors. <h3>Background:</h3> Ischemic stroke is the third leading cause of death in women. Women have unique risk factors for ischemic stroke. Iron deficiency anemia disproportionately affects premenopausal women and has previously been identified to be associated with ischemic stroke. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 39-year old woman with hypertension and menorrhagia presented with left leg weakness and dizziness. Labs revealed a hemoglobin of 5.9g/dL, a unremarkable hypercoagulable work up, transesophageal echo, urine toxicology, rheumatological evaluation, and MRA brain vessel wall imaging. An ultrasound of her uterus revealed a pelvic fibroid measuring 6.5cm and MRI brain revealed a small right anterior cerebral artery territory infarction. A 46-year-old woman with chronic iron deficiency anemia with a hemoglobin of 6.8g/dL who presented with left mild sided weakness and was found to have a right MCA M3 occlusion by CT angiography of the head. She received intravenous tenecteplase and underwent decompressive craniectomy for a right temporal infarct associated with cerebral edema seen on MRI brain. Investigations revealed a normal hemoglobin electrophoresis, urine toxicology, hypercoagulable evaluation, rheumatological evaluation and transesophageal echo. A 43 year old woman presented with diplopia secondary to a vertical gaze palsy. MRI brain revealed an infarct in the left thalamus, cerebral peduncle, and midbrain. Cerebral angiography, transesophageal echocardiogram, urine toxicology, rheumatological evaluation, and hypercoagulable work up were unremarkable. Hemoglobin was 7.2g/dL on presentation and an EGD revealed an antral and duodenal ulcer. All three patients received packed RBC transfusions, iron replacement therapy and discontinuation of aspirin until hemoglobin stabilized. <h3>Conclusions:</h3> Iron deficiency anemia may be an important yet under-recognized risk factor for acute ischemic stroke and should be treated aggressively in premenopausal women. Further studies are warranted. <b>Disclosure:</b> Dr. Imam has nothing to disclose. Dr. Salahuddin has nothing to disclose.

Appropriateness of packed red blood cells transfusions in chronic anemic patients in the emergency department: the TRANSFUS-ED retrospective analysis

Patients suffering from chronic anemia can benefit from scheduled transfusions of packed red blood cells (PRBCs), while urgent transfusions have specific indications. These patients frequently seek medical attention in the emergency department (ED), where they can be inappropriately transfused, but research in this field is limited. This study aimed to assess the appropriateness of PRBCs transfusions in chronic anemic patients in the ED. A retrospective analysis was performed on patients who accessed the ED of the Azienda Ospedaliera di Padova (Padova, Italy) between 2016 and 2019 and received PRBCs transfusions. Patients aged ≥ 18 years old and with chronic anemia were included, while those with acute anemia or admitted to the hospital after the transfusion were excluded. Chronic anemia was defined as satisfying one of the following in the past medical history: diagnosis of chronic anemia; two or more previous blood samplings demonstrating anemia; periodic transfusions. As primary outcome, the appropriateness of transfusions was assessed according to the American Association of Blood Banks (AABB) 2016 criteria, using the recommended threshold of 7 g/dL for hemodynamically stable adults and 8 g/dL for patients with pre-existing cardiovascular disease. Out of 1153 transfusions, 344 transfusions were included in the study. According to our criteria, 139 (40.4%) patients were inappropriately transfused, resulting in a total estimated cost of 54,528.71 € in the study period. This study showed that transfusions in chronic anemic patients are recurrent events in the ED and are frequently inappropriate. A possible explanation could be the lack of a well-structured primary care network granting periodic transfusions in ambulatory centers. In the future, implementing and improving chronic anemic patients’ access to transfusion services through dedicated pathways could reduce the burden on the ED and also decrease costs.

Standard Versus Restrictive Transfusion Strategy for Pediatric Cardiac ECLS Patients: Single Center Retrospective Cohort Study.

This retrospective cohort study aimed to compare blood component transfusion before and after the implementation of a restrictive transfusion strategy (RTS) in pediatric cardiac Extracorporeal Life Support (ECLS) patients. The study included children admitted to the pediatric cardiac intensive care unit (PCICU) at the Stollery Children's Hospital who received ECLS between 2012 and 2020. Children on ECLS between 2012 and 2016 were treated with standard transfusion strategy (STS), while those on ECLS between 2016 and 2020 were treated with RTS. During the study, 203 children received ECLS. Daily median (interquartile range [IQR]) packed red blood cell (PRBC) transfusion volume was significantly lower in the RTS group; 26.0 (14.4-41.5) vs. 41.5 (26.6-64.4) ml/kg/day, p value <0.001. The implementation of a RTS led to a median reduction of PRBC transfusion of 14.5 (95% CI: 6.70-21.0) ml/kg/day. Similarly, the RTS group received less platelets: median (IQR) 8.4 (4.50-15.0) vs. 17.5 (9.40-29.0) ml/kg/day, p value <0.001. The implementation of a RTS resulted in a median reduction of platelet transfusion of 9.2 (95% CI: 5.45-13.1) ml/kg/day. The RTS resulted in less median (IQR) fluid accumulation in the first 48 hours: 56.7 (2.30-121.0) vs. 140.4 (33.8-346.2) ml/kg, p value = 0.001. There were no significant differences in mechanical ventilation days, PCICU/hospital days, or survival. The use of RTS resulted in lower blood transfusion volumes, with similar clinical outcomes.

Effect of packed red blood cell transfusion on the prognosis of patients with upper gastrointestinal bleeding: a retrospective analysis of eICU-CRD v2.0 multicenter critically ill patients database

Abstract Background The effects of packed red blood cell (PRBC) transfusion on the prognosis of patients with upper gastrointestinal bleeding (UGIB), particularly on the 30-day mortality rate, are unclear. This study aimed to determine the prognostic influence of PRBC transfusion in patients with UGIB with different hemoglobin (Hb) levels. Methods The subjects in this study were selected from the Philips Electronic ICU Collaborative Research Database Version 2.0 multicenter critically ill patient database from January 2014 to December 2015. A total of 4689 patients were included in this study. The Hb levels were divided into 3 groups: Hb &lt;6 g/dL (Group 1), 6 g/dL ≤ Hb &lt; 8 g/dL (Group 2), and Hb ≥8 g/dL (Group 3). Based on the administration of PRBC transfusion, each group was subdivided into PRBC and non-PRBC groups. Results A total of 4689 patients were enrolled in the study, including 825, 2195, and 1669 patients in Groups 1, 2, and 3, respectively. Furthermore, the PRBC and non-PRBC groups consisted of 1847 and 2842 patients, respectively. There was no significant difference in the 30-day mortality rate between Group 1 and Group 2 or between the PRBC and non-PRBC subgroups. In Group 3, the 30-day mortality rate of patients who received transfusion was higher than that of patients who did not (13.29% vs 9.14%, P = 0.029). For the PRBC group, the difference in 30-day mortality rate was not statistically significant among the 3 groups, whereas for the non-PRBC group, the 30-day mortality rate in Group 3 was the lowest, and there was a significant difference among the 3 groups (P = 0.003). There was no significant difference in the subgroup analysis of bleeding at different sites and etiologies. Conclusion Packed red blood cell transfusion does not improve prognosis or reduce mortality in patients with UGIB but may increase mortality in patients with Hb levels greater than 8 g/dL.

Haematological Trends and Transfusion during Adult Extracorporeal Membrane Oxygenation: A Single Centre Study.

Patient demographics, haematological and coagulation parameters, plasma haemoglobin and fibrinogen concentrations, platelet count, the international normalised ratio (INR), the activated partial thromboplastin time (APTT), and blood product transfusion data from 138 patients who received ECMO in a single high-volume centre were analysed. Ninety-two patients received venoarterial (VA) ECMO and 46 patients received venovenous (VV) ECMO. The median (IQR) duration of VA, and VV ECMO was 8 (5-13) days and 13 (8-23) days, respectively. There were significant reductions in haemoglobin, the platelet count, and the fibrinogen concentration upon initiation of ECMO. On average, over time, patients on VV ECMO had platelet counts 44 × 109/L higher than those on VA ECMO (p ≤ 0.001). Fibrinogen and APTT did not vary significantly based on the mode of ECMO (p = 0.55 and p = 0.072, respectively). A platelet count < 50 × 109/L or a fibrinogen level < 1.8 g/L was associated with 50% chance of PRBC transfusion, regardless of the ECMO type, and packed red blood cell (PRBC) transfusion was more common with VA ECMO. APTT was predictive of the transfusion requirement, and the decrement in APTT was discriminatory between VVECMO survivors and nonsurvivors. ECMO support is associated with reductions in haemoglobin, platelet count, and fibrinogen. Patients supported with VA ECMO are more likely to receive a PRBC transfusion compared to those on VV ECMO. Thrombocytopaenia, hypofibrinogenaemia, and anticoagulation effect the likelihood of requiring PRBC transfusion. Further research is needed to define optimal blood management during ECMO, including appropriate transfusion triggers and the anticoagulation intensity.