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Patient selection for pediatric extracorporeal membrane oxygenation (ECMO) support has broadened over the years to include children with pre-existing neurologic morbidities. We aimed to determine the prevalence and nature of pre-ECMO neurologic disorders or disability and investigate the association between pre-ECMO neurologic disorders or disability and mortality and unfavorable neurologic outcome.Multicenter retrospective observational cohort study.Eight hospitals reporting to the Pediatric ECMO Outcomes Registry between October 2011 and June 2019.Children younger than 18 years supported with venoarterial or venovenous ECMO.The primary exposure was presence of pre-ECMO neurologic disorders or moderate-to-severe disability, defined as Pediatric Cerebral Performance Category (PCPC) or Pediatric Overall Performance Category (POPC) 3-5. The primary outcome was unfavorable outcome at hospital discharge, defined as in-hospital mortality or survival with moderate-to-severe disability (discharge PCPC 3-5 with deterioration from baseline).Of 598 children included in the final cohort, 68 of 598 (11%) had a pre-ECMO neurologic disorder, 70 of 595 (12%) had a baseline PCPC 3-5, and 189 of 592 (32%) had a baseline POPC 3-5. The primary outcome of in-hospital mortality ( n = 267) or survival with PCPC 3-5 with deterioration from baseline ( n = 39) was observed in 306 of 598 (51%). Overall, one or more pre-ECMO neurologic disorders or disability were present in 226 of 598 children (38%) but, after adjustment for age, sex, diagnostic category, pre-ECMO cardiac arrest, and ECMO mode, were not independently associated with increased odds of unfavorable outcome (unadjusted odds ratio [OR], 1.34; 95% CI, 1.07-1.69; multivariable adjusted OR, 1.30; 95% CI, 0.92-1.82).In this exploratory study using a multicenter pediatric ECMO registry, more than one third of children requiring ECMO support had pre-ECMO neurologic disorders or disability. However, pre-existing morbidities were not independently associated with mortality or unfavorable neurologic outcomes at hospital discharge after adjustment for diagnostic category and other covariates.

Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock.

Background The use of low-titer group O whole blood is increasing. To reduce wastage, unused units can be converted to packed red blood cells. Supernatant is currently discarded post-conversion; however, it could be a valuable transfusable product. The aim of this study was to evaluate supernatant prepared from late-storage low-titer group O whole blood being converted to red blood cells, hypothesizing it will have higher hemostatic activity compared to fresh never-frozen liquid plasma. Methods Low-titer group O whole blood supernatant (n=12) prepared on storage day 15 was tested on day 15, 21, and 26 and liquid plasma (n=12) on 3, 15, 21, and 26. Same day assays included cell counts, rotational thromboelastometry, and thrombin generation. Centrifuged plasma from units was banked for microparticle characterization, conventional coagulation, clot structure, hemoglobin, and additional thrombin generation assays. Results Low-titer group O whole blood supernatant contained more residual platelets and microparticles compared to liquid plasma. At day 15, low-titer group O whole blood supernatant elicited a faster intrinsic clotting time compared to liquid plasma (257 +/- 41 vs. 299 +/- 36 seconds, p=0.044), and increased clot firmness (49 +/- 9 vs. 28 +/- 5 mm, p Conclusions Plasma supernatant produced from late-storage low-titer group O whole blood shows comparable, if not enhanced, in vitro hemostatic efficacy to liquid plasma.

BackgroundCommunity-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce.MethodsWe evaluated children and adolescents aged ResultsOf the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01–1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05–1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36–2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15–4.62]) was associated with bacterial coinfection.ConclusionsCommunity-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.

OBJECTIVE: Primary objective: to determine if transfusion of short-storage red blood cells (RBCs) compared to standard-issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective: to assess if RBC transfusion was independently associated with delirium/coma. DESIGN: This study was performed in two stages. First we compared patients receiving either short-storage or standard RBCs in a multi-institutional prospective randomized controlled trial (RCT). Then we compared all transfused patients in the RCT to a single-center cohort of non-transfused patients matched for confounders of delirium/coma. SETTING: Twenty academic pediatric intensive care units who participated in the Age of Transfused Blood in Critically Ill Children (ABC-PICU) trial. PATIENTS: Children 3-days to 16-years of age who were transfused RBCs within the first seven days of admission. INTERVENTIONS: Subjects were randomized to either short-storage RBC study arm (defined as RBCs stored for up to seven days) or standard-issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12-hours after transfusion for up to three days. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was development of delirium/coma within three days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually-matched non-transfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short-storage RBCs and 77 to standard-issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%, p=0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than 8-fold higher than in the non-transfused matched cohort, even after controlling for hemoglobin (aOR 8.9; CI 2.8–28.4, p

Background Accurate assessment of hemostatic function is essential to guide care in critically ill children with acute and acquired coagulopathies. Thrombin generation (TG) provides a global assessment of procoagulant and anticoagulant factors and is commonly used in hemostasis research laboratories. Our objective was to determine the correlation of clinically available hemostasis assays with TG in critically ill children. Methods Children (3 kg in weight) in the intensive care unit were enrolled from March 2016 to December 2019 in a prospective 2-center study. Coagulation tests were prothrombin time, activated thromboplastin time, anti-Xa assay, viscoelastic assays (thromboelastography [TEG], rotational thromboelastometry [ROTEM]), and TG (induced by 20 pM tissue factor in platelet poor plasma and reported as endogenous thrombin potential [ETP; nM*min]). Data are reported as median (interquartile range) or Spearman coefficient (ρ). Results Patients (n = 106, age 10.2 years [3.8–15.3]) were divided into 3 groups: (a) no anticoagulation (n = 46), (b) anticoagulation (unfractionated heparin) without extracorporeal life support (n = 34), or (c) with extracorporeal life support (n = 26). ETP was decreased in anticoagulated compared to non-anticoagulated patients (group 1: 902.4 [560.8–1234], group 2: 315.6 [0.0–962.2], group 3: 258.5 [0.0–716.6]; P Conclusions Standard and viscoelastic assays have varying correlation with TG in critically ill children. TEG-K time had the most consistent moderate correlation with ETP across all groups.

Research evaluating hemostatic agents for the treatment of clinically significant bleeding has been hampered by inconsistency and lack of standardized primary clinical trial outcomes. Clinical trials of hemostatic agents in both cardiac surgery and mechanical circulatory support, such as extracorporeal membrane oxygenation and ventricular assist devices, are examples of studies that lack implementation of universally accepted outcomes.A subgroup of experts convened by the National Heart, Lung, and Blood Institute and the US Department of Defense developed consensus recommendations for primary outcomes in cardiac surgery and mechanical circulatory support.For cardiac surgery the primary efficacy endpoint of total allogeneic blood products (units vs mL/kg for pediatric patients) administered intraoperatively and postoperatively through day 5 or hospital discharge is recommended. For mechanical circulatory support outside the perioperative period the recommended primary outcome for extracorporeal membrane oxygenation is a 5-point ordinal score of thrombosis and bleeding severity adapted from the Common Terminology Criteria for Adverse Events version 5.0. The recommended primary endpoint for ventricular assist device is freedom from disabling stroke (Common Terminology Criteria for Adverse Events AE ≥ grade 3) through day 180.The proposed composite risk scores could impact the design of upcoming clinical trials and enable comparability of future investigations. Harmonizing and disseminating global consensus definitions and management guidelines can also reduce patient heterogeneity that would confound standardized primary outcomes in future research.

Negative reinforcement mechanisms, wherein individuals smoke at regular intervals to ameliorate craving and withdrawal, are integral to persistent smoking. This is consistent with the behavior of dependent smokers but does not fully account for the behavior of intermittent smokers, who do not smoke enough to maintain steady nicotine levels. This study examined the independent and combined impacts of nicotine and tobacco consumption on cigarette craving, withdrawal, and subsequent smoking behavior in 18 nondependent light and intermittent smokers (LITS) and 23 daily, dependent smokers (DDS). Participants administered conventional nicotine-containing cigarettes (NC; 18.9 mg nicotine; 1.41 mg deliverable), reduced nicotine content cigarettes (RNC; 0.4 mg nicotine, 0.05 mg deliverable), nicotine inhalers (NI; 10 mg nicotine, 4 mg deliverable), or nicotine-free inhalers (NFI) across 4 sessions following overnight abstinence. Participants rated craving and withdrawal before and after product administration, then completed a cigarette self-administration task. For cigarette self-administration, neither smoking status nor product affected latency to initiate smoking; however, LITS were more likely to abstain from smoking and administered fewer puffs than DDS. Across participants, pharmacologically active products (NC, RNC, NI) were associated with fewer cigarette puffs than the NFI. For subjective measures, only cigarettes (NC, RNC) reduced craving in both LITS and DDS. NC, RNC, and NI reduced withdrawal in DDS, while withdrawal remained at floor levels across time points among LITS. While subjective ratings and smoking behavior were largely comparable across LITS and DDS, differing patterns of withdrawal symptoms suggest that dependent smoking is motivated by negative reinforcement while nondependent smoking is not. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Platelet transfusion is a potentially life-saving therapy for actively bleeding patients, ranging from those undergoing planned surgical procedures to those suffering unexpected traumatic injuries. Platelets are currently stored at room temperature (20°C–24°C) with a maximum storage duration of 7 days after donation. The CHIlled Platelet Study trial will compare the efficacy and safety of standard room temperature–stored platelets with platelets that are cold-stored (1°C–6°C), that is, chilled, with a maximum of storage up to 21 days in adult and pediatric patients undergoing complex cardiac surgical procedures. Methods/Results: CHIlled Platelet Study will use a Bayesian adaptive design to identify the range of cold storage durations for platelets that are non-inferior to standard room temperature–stored platelets. If cold-stored platelets are non-inferior at durations greater than 7 days, a gated superiority analysis will identify durations for which cold-stored platelets may be superior to standard platelets. We present example simulations of the CHIlled Platelet Study design and discuss unique challenges in trial implementation. The CHIlled Platelet Study trial has been funded and will be implemented in approximately 20 clinical centers. Early randomization to enable procurement of cold-stored platelets with different storage durations will be required, as well as a platelet tracking system to eliminate platelet wastage and maximize trial efficiency and economy. Discussion: The CHIlled Platelet Study trial will determine whether cold-stored platelets are non-inferior to platelets stored at room temperature, and if so, will determine the maximum duration (up to 21 days) of storage that maintains non-inferiority. Trial registration: ClinicalTrials.gov, NCT04834414

In paediatric trauma patients, there are limited prospective data regarding blood components and mortality, with some literature suggesting decreased mortality with high ratios of plasma and platelets to red blood cells (RBCs) in massive transfusions; however, most paediatric massive transfusions occur for non-traumatic aetiologies and few studies assess blood product ratios in these children. This study's objective was to evaluate whether high blood product ratios or low deficits conferred a survival benefit in children with non-traumatic life-threatening bleeding.This is a secondary analysis of the five-year, multicentre, prospective, observational massive transfusion epidemiology and outcomes in children study of children with life-threatening bleeding from US, Canadian and Italian medical centres. Primary interventions were plasma:RBC and platelets:RBC (high ratio ≥1:2 ml/kg) and plasma and platelet deficits. The primary outcome was mortality at 6 h, 24 h and 28 days. Multivariate logistic regression models were used to determine independent associations with mortality.A total of 222 children were included from 24 medical centres: 145 children (median [interquartile range] age 2.1 years [0.3-11.8]) with operative bleeding and 77 (8.0 years [1.2-14.7]) with medical bleeding. In adjusted analyses, neither blood product ratios nor deficits were associated with mortality at 6 h, 24 h or 28 days.This paper addresses a lack of prospective data in children regarding optimal empiric massive transfusion strategies in non-traumatic massive haemorrhage and in finding no decrease in mortality with high plasma or platelet to RBC ratios or lower deficits supports an exploratory analysis for mortality.

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. MEASURES 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.

High-quality evidence guiding optimal transfusion and other supportive therapies to reduce bleeding is needed to improve outcomes for patients with either severe bleeding or hemostatic disorders that are associated with poor outcomes. Alongside challenges in performing high-quality clinical trials in patient populations who are at risk of bleeding or who are actively bleeding, the interpretation of research evaluating hemostatic agents has been limited by inconsistency in the choice of primary trial outcomes. This lack of standardization of primary endpoints or outcomes decreases the ability of clinicians to assess the validity of endpoints and compare research results across studies, impairs meta-analytic efforts, and, ultimately, delays the translation of research results into clinical practice. To address this challenge, an international panel of experts was convened by the National Heart Lung and Blood Institute and the US Department of Defense on September 23 and 24, 2019, to develop expert opinion, consensus-based recommendations for primary clinical trial outcomes for pivotal trials in pediatric and adult patients with six categories in various clinical settings. This publication documents the conference proceedings from the workshop funded by the National Heart Lung and Blood Institute and the US Department of Defense that consolidated expert opinion regarding clinically meaningful outcomes across a wide range of disciplines to provide guidance for outcomes of future trials of hemostatic products and agents for patients with active bleeding.

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.

The clinical state of shock constitutes a relative or absolute deficiency of circulating volume for adequate oxygen delivery to meet the metabolic demands.1 Although shock states differ in epidemiology, etiology, and pathophysiologic pathways, a common denominator of shock is endothelial barrier dysfunction.2, 3 Different kinds of shock states, such as occurring after major surgery, trauma, and in sepsis, can result in strong pro‐inflammatory host responses with ensuing endothelial hyperpermeability.4, 5, 6 Loss of endothelial barrier results in leakage of fluid into surrounding tissue, contributing to edema, tissue hypoxia, and organ failure.6 This loss of fluids further aggravates the intravascular circulatory volume deficiency during shock. Obviously, septic and traumatic shock are different entities, with different etiologies and differences in initiation of host response and coagulation response. However, endothelial activation with loss of endothelial barrier integrity is a common finding in both shock states. In trauma‐induced shock, current resuscitation strategies consist of the early transfusion of whole blood or a balanced ratio of plasma, platelets, and red blood cells.7, 8 The aim of resuscitation is to ensure adequate oxygen delivery and to correct coagulopathy. Plasma transfusion may play a key role, as trials point toward improved survival with high dose or early use of plasma transfusion compared to standard care.9, 10, 11 Upon reaching surgical hemostasis, it is general practice to stop transfusion. However, as a result of ongoing inflammation and endothelial activation, patients can continue to be fluid dependent, which is often responded to with crystalloids. However, liberal use of crystalloids in traumatic hemorrhagic shock is associated with increased mortality and increased endothelial permeability, inflammation, and reduced perfusion of vital organs.12, 13, 14 In septic shock, the primary treatment of shock is volume resuscitation with crystalloid or colloids, as advocated in guidelines.15 However, comparable to traumatic hemorrhagic shock, use of a restrictive fluid balance reduces the occurrence of organ failure as well as mortality in sepsis.16, 17, 18 most likely, the association between the amount of infused volume and adverse outcome in shock states is related to increased shedding of the glycocalix, breakdown of adherent junctions, and tight junctions resulting in an increased gradient of leakage over the hyper permeable endothelium.19 Taken together, due to a relative or absolute deficiency of intravascular volume, patients with shock are likely to need volume expansion to maintain perfusion pressure. This poses a challenge to the treatment of shock, as fluid therapy is both a cornerstone of therapy as well as a foe. Different fluids may have differential effects on endothelial integrity. Low‐protein‐content fluids seem to aggravate shedding of glycocalix,20 whereas protein‐rich fluids such as plasma may be superior to normal saline in protecting the glycocalix and endothelial barrier function.21 Transfusion with plasma as a volume expander in shock may seem controversial at first, but one needs to consider that despite the fact that plasma is transfused in millions of patients annually, there currently is limited understanding of its mechanisms of action. In traumatic blood loss, transfusion of plasma may improve survival by decreasing exsanguination.7, 10 The common perception is that plasma is a pro‐coagulant blood product, by replenishing coagulation factors. However, as plasma contains coagulation factors but also anticoagulant proteins, the net effect of plasma on coagulation may be neutral. In line with this, plasma transfusion increases the amount of coagulation factors as well as levels of anti‐coagulant proteins,22 resulting in unchanged thrombin generation, at least in non‐bleeding critically ill patients with an inflammatory‐driven consumption coagulopathy. In patients with traumatic hemorrhagic shock, it is not apparent whether the mechanism of effect of plasma is directly related to the correction of coagulopathy.23 In rats with hemorrhagic shock, deranged thrombin formation was somewhat restored with resuscitation with plasma but not with crystalloids, but whether this relates to prevention of dilutional coagulopathy or to a specific pro‐coagulant effect of plasma is not clear.24, 25 Other mechanisms of the protective effect of plasma may be at hand. These may include preservation of the glycocalix, decreasing inflammation and decreasing endothelial leak. This review aims to discuss the potential of plasma as a resuscitation fluid in shock, with an emphasis on possible mechanisms of benefit on the activated endothelium. Studies comparing plasma with other fluids on (markers of) endothelial integrity have found effects both in (models of) trauma‐induced shock and in septic shock. As loss of endothelial integrity may be a common denominator of shock, we will discuss both these shock states.

Screening for the risk of thromboembolism (TE) due to tranexamic acid (TXA) in patients with severe traumatic injury has not been performed in randomized clinical trials. Our objective was to determine if TXA dose was independently-associated with thromboembolism.This is a secondary analysis of a single-center, double-blinded, randomized controlled trial comparing placebo to a 2-g or 4-g intravenous TXA bolus dose in trauma patients with severe injury. We used multivariable discrete-time Cox regression models to identify associations with risk for thromboembolic events within 30 days post-enrollment. Event curves were created using discrete-time Cox regression.There were 50 patients in the placebo group, 49 in the 2-g, and 50 in the 4-g TXA group. In adjusted analyses for thromboembolism, a 2-g dose of TXA had an hazard ratio (HR, 95% confidence interval [CI]) of 3.20 (1.12-9.11) (p = .029), and a 4-g dose of TXA had an HR (95% CI) of 5.33 (1.94-14.63) (p = .001). Event curves demonstrated a higher probability of thromboembolism for both doses of TXA compared to placebo. Other parameters independently associated with thromboembolism include time from injury to TXA administration, body mass index, and total blood products transfused.In patients with severe traumatic injury, there was a dose-dependent increase in the risk of at least one thromboembolic event with TXA. TXA should not be withheld, but thromboembolism screening should be considered for patients receiving a dose of at least 2-g TXA intravenously for traumatic hemorrhage.