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Objectives: To assess if transfusion with low-titer group O whole blood (LTOWB) is associated with improved early and/or late survival compared with component blood product therapy (CT) in bleeding trauma patients., Data Sources: A systematic search of PubMed, CINAHL, and Web of Science was performed from their inception through December 1, 2023. Key terms included injury, hemorrhage, bleeding, blood transfusion, and whole blood., Study Selection: All studies comparing outcomes in injured civilian adults and children who received LTOWB versus CT were included., Data Extraction: Data including author, publication year, sample size, total blood volumes, and clinical outcomes were extracted from each article and reported following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Main outcomes were 24-hour (early) and combined 28-day, 30-day, and in-hospital (late) mortality rates between recipients of LTOWB versus CT, which were pooled using random-effects models., Data Synthesis: Of 1297 studies reviewed, 24 were appropriate for analysis. Total subjects numbered 58,717 of whom 5,164 received LTOWB. Eleven studies included adults-only, seven included both adults and adolescents, and six only included children. The median (interquartile range) age for patients who received LTOWB and CT was 35 years (24-39) and 35.5 years (23-39), respectively. Overall, 14 studies reported early mortality and 22 studies reported late mortality. LTOWB was associated with improved 24-hour survival (risk ratios [RRs] [95% CI] = 1.07 [1.03-1.12]) and late (RR [95% CI] = 1.05 [1.01-1.09]) survival compared with component therapy. There was no evidence of small study bias and all studies were graded as a moderate level of bias., Conclusions: These data suggest hemostatic resuscitation with LTOWB compared with CT improves early and late survival outcomes in bleeding civilian trauma patients. The majority of subjects were injured adults; multicenter randomized controlled studies in injured adults and children are underway to confirm these findings., Competing Interests: Dr. Spinella is a consultant for Cerus and Hemanext, on the advisory board for Haima and Octapharma, and is a Co-Founder and Chief Medical Officer of Kalocyte. He also has funding from Biomedical Advanced Research and Development Authority to perform a trial examining the safety and efficacy of whole blood. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: To assess the impact of antifibrinolytics in children with life-threatening hemorrhage., Design: Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a prospective observational study of children with life-threatening bleeding events., Setting: Twenty-four children's hospitals in the United States, Canada, and Italy., Patients: Children 0-17 years old who received greater than 40 mL/kg of total blood products over 6 hours or were transfused under activation of massive transfusion protocol., Intervention/exposure: Children were compared according to receipt of antifibrinolytic medication (tranexamic acid or aminocaproic acid) during the bleeding event., Measurements and Main Results: Patient characteristics, medications administered, and clinical outcomes were analyzed using Cox proportional hazard and Kaplan-Meier survival analysis. The primary outcome was 24-hour mortality. Of 449 patients analyzed, median age was 7 years (2-15 yr), and 55% were male. The etiology of bleeding was 46% traumatic, 34% operative, and 20% medical. Twelve percent received antifibrinolytic medication during the bleeding event (n = 54 unique subjects; n = 18 epsilon aminocaproic acid, n = 35 tranexamic acid, and n = 1 both). The antifibrinolytic group was comparable with the nonantifibrinolytic group on baseline demographic and physiologic parameters; the antifibrinolytic group had longer massive transfusion protocol duration, received greater volume blood products, and received factor VII more frequently. In the antifibrinolytic group, there was significantly less 6-hour mortality overall (6% vs 17%; p = 0.04) and less 6-hour mortality due to hemorrhage (4% vs 14%; p = 0.04). After adjusting for age, bleeding etiology, Pediatric Risk of Mortality score, and plasma deficit, the antifibrinolytic group had decreased mortality at 6- and 24-hour postbleed (adjusted odds ratio, 0.29 [95% CI, 0.09-0.93]; p = 0.04 and adjusted odds ratio, 0.45 [95% CI, 0.21-0.98]; p = 0.04, respectively)., Conclusions: Administration of antifibrinolytic medications during the life-threatening event was independently associated with improved 6- and 24-hour survivals in bleeding children. Consideration should be given to use of antifibrinolytics in pediatric patients with life-threatening hemorrhage., Competing Interests: Dr. Spinella is a consultant for Secure Transfusion Services, Hemanext, and Haima; Dr. Leonard receives royalty payments from UpToDate; Dr. Josephson is a consultant for Immucor, Octapharma, and Cellphine, and has an unrestricted grant from Medtronics. Drs. Spinella, Leonard, and Josephson received support for article research from the National Institutes of Health. Dr. Leonard’s institution received funding from National Institutes of Child Health and Development. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: The purpose of our study was to describe children with life-threatening bleeding., Design: We conducted a prospective observational study of children with life-threatening bleeding events., Setting: Twenty-four childrens hospitals in the United States, Canada, and Italy participated., Subjects: Children 0-17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under massive transfusion protocol were included., Interventions: Children were compared according bleeding etiology: trauma, operative, or medical., Measurements and Main Results: Patient characteristics, therapies administered, and clinical outcomes were analyzed. Among 449 enrolled children, 55.0% were male, and the median age was 7.3 years. Bleeding etiology was 46.1% trauma, 34.1% operative, and 19.8% medical. Prior to the life-threatening bleeding event, most had age-adjusted hypotension (61.2%), and 25% were hypothermic. Children with medical bleeding had higher median Pediatric Risk of Mortality scores (18) compared with children with trauma (11) and operative bleeding (12). Median Glasgow Coma Scale scores were lower for children with trauma (3) compared with operative (14) or medical bleeding (10.5). Median time from bleeding onset to first transfusion was 8 minutes for RBCs, 34 minutes for plasma, and 42 minutes for platelets. Postevent acute respiratory distress syndrome (20.3%) and acute kidney injury (18.5%) were common. Twenty-eight-day mortality was 37.5% and higher among children with medical bleeding (65.2%) compared with trauma (36.1%) and operative (23.8%). There were 82 hemorrhage deaths; 65.8% occurred by 6 hours and 86.5% by 24 hours., Conclusions: Patient characteristics and outcomes among children with life-threatening bleeding varied by cause of bleeding. Mortality was high, and death from hemorrhage in this population occurred rapidly., Competing Interests: Drs. Leonard’s, Nair’s, and Spinella’s institutions received funding from the National Heart, Lung, and Blood Institute (NHLBI). Drs. Leonard, Josephson, Davis, Fitzgerald, Muszynski, Steiner, Wills, and Spinella received support for article research from the National Institutes of Health (NIH). Dr. Josephson received funding from Immucor, LLC, and Octapharma. Drs. Allen’s, Hewes’s, Rouse’s, and Steiner’s institutions received funding from the NIH grant administered by Washington University in St. Louis. Drs. Davis’, Nair’s, and Steiner’s institutions received funding from an NIH Exploratory/Developmental Research Grant Award (R21). Dr. Finkelstein received funding from Trauma In Kids Course via the Royal College of Physicians and Surgeons of Canada and the Pediatric Trauma Society from New York Presbyterian Weill Cornell, Carilion Clinic, and Texas Children’s Hospital, Society of Critical Care Medicine as a Faculty Instructor, Giblin, Combs, Schwartz, Cunningham, & Scarpa, LLC, Aaronson Rappaport Feinstein & Deutsch, LLP, and Ruprecht Hart Weeks & Ricciardulli, LLP; he disclosed that his wife has stock in Pfizer and Proctor & Gamble. Drs. Fitzgerald’s, Muszynski’s, and Spinella’s institutions received funding from the NIH. Drs. Johnson’s and Wills’ institutions institution received funding from Massive Transfusion Epidemiology and Outcomes in Children Study, 5R21HL128863-02 NHLBI. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)