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Shock index as predictor of massive transfusion and mortality in patients with trauma: a systematic review and meta-analysis
Carsetti, A., Antolini, R., Casarotta, E., Damiani, E., Gasparri, F., Marini, B., Adrario, E., Donati, A.
Critical Care (London, England). 2023;27(1):85
Abstract
BACKGROUND Management of bleeding trauma patients is still a difficult challenge. Massive transfusion (MT) requires resources to ensure the safety and timely delivery of blood products. Early prediction of MT need may be useful to shorten the time process of blood product preparation. The primary aim of this study was to assess the accuracy of shock index to predict the need for MT in adult patients with trauma. For the same population, we also assessed the accuracy of SI to predict mortality. METHODS This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. We performed a systematic search on MEDLINE, Scopus, and Web of Science from inception to March 2022. Studies were included if they reported MT or mortality with SI recorded at arrival in the field or the emergency department. The risk of bias was assessed using the QUADAS-2. RESULTS Thirty-five studies were included in the systematic review and meta-analysis, for a total of 670,728 patients. For MT the overall sensibility was 0.68 [0.57; 0.76], the overall specificity was 0.84 [0.79; 0.88] and the AUC was 0.85 [0.81; 0.88]. Positive and Negative Likelihood Ratio (LR+; LR-) were 4.24 [3.18-5.65] and 0.39 [0.29-0.52], respectively. For mortality the overall sensibility was 0.358 [0.238; 0.498] the overall specificity 0.742 [0.656; 0.813] and the AUC 0.553 (confidence region for sensitivity given specificity: [0.4014; 0.6759]; confidence region for specificity given sensitivity: [0.4799; 0.6332]). LR+ and LR- were 1.39 [1.36-1.42] and 0.87 [0.85-0.89], respectively. CONCLUSIONS Our study demonstrated that SI may have a limited role as the sole tool to predict the need for MT in adult trauma patients. SI is not accurate to predict mortality but may have a role to identify patients with a low risk of mortality.
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The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma
Hayakawa, M., Tagami, T., Kudo, D., Ono, K., Aoki, M., Endo, A., Yumoto, T., Matsumura, Y., Irino, S., Sekine, K., et al
Journal of intensive care. 2023;11(1):34
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Editor's Choice
Abstract
BACKGROUND The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. METHODS This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. RESULTS The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. CONCLUSIONS Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. TRIAL REGISTRATION NUMBER umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.
PICO Summary
Population
Adult patients with severe trauma at risk of major bleeding, enrolled in the RESTRIC cluster-randomized, crossover trial at 22 tertiary emergency medical institutions in Japan (n= 422).
Intervention
Restrictive transfusion strategy (n= 222).
Comparison
Liberal transfusion strategy (n= 200).
Outcome
The restrictive and liberal red blood cell strategy groups included 216 and 195 patients in the intention-to-treat analysis, respectively. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. The 28-day survival rates of patients in the restrictive (n= 216) and liberal (n= 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02; 95% confidence interval [0.49, 2.13]. Significant non-inferiority was not observed. Transfusion volumes and haemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days.
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Transfusion Guidelines in Traumatic Brain Injury: A Systematic Review and Meta-Analysis of the Currently Available Evidence
Montgomery EY, Barrie U, Kenfack YJ, Edukugho D, Caruso JP, Rail B, Hicks WH, Oduguwa E, Pernik MN, Tao J, et al
Neurotrauma reports. 2022;3(1):554-568
Abstract
Our study aims to provide a synthesis of the best available evidence on the hemoglobin (hgb) red blood cell (RBC) transfusion thresholds in adult traumatic brain injury (TBI) patients, as well as describing the risk factors and outcomes associated with RBC transfusion in this population. A systematic review and meta-analysis was conducted using PubMed, Google Scholar, and Web of Science electronic databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess articles discussing RBC transfusion thresholds and describe complications secondary to transfusion in adult TBI patients in the perioperative period. Fifteen articles met search criteria and were reviewed for analysis. Compared to non-transfused, TBI patients who received transfusion tended to be primarily male patients with worse Injury Severity Score (ISS) and Glasgow Coma Scale. Further, the meta-analysis corroborated that transfused TBI patients are older (p = 0.04), have worse ISS scores (p = 0.001), receive more units of RBCs (p = 0.02), and have both higher mortality (p < 0.001) and complication rates (p < 0.0001). There were no differences identified in rates of hypertension, diabetes mellitus, and Abbreviated Injury Scale scores. Additionally, whereas many studies support restrictive (hgb <7 g/dL) transfusion thresholds over liberal (hgb <10 g/dL), our meta-analysis revealed no significant difference in mortality between those thresholds (p = 0.79). Current Class B/C level III evidence predominantly recommends against a liberal transfusion threshold of 10 g/dL for TBI patients (Class B/C level III), but our meta-analysis found no difference in survival between groups. There is evidence suggesting that an intermediate threshold between 7 and 9 g/dL, reflecting the physiological oxygen needs of cerebral tissue, may be worth exploring.
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Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial
Crombie N, Doughty HA, Bishop JRB, Desai A, Dixon EF, Hancox JM, Herbert MJ, Leech C, Lewis SJ, Nash MR, et al
The Lancet. Haematology. 2022
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Editor's Choice
Abstract
BACKGROUND Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock. METHODS Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938. FINDINGS From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths. INTERPRETATION The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders. FUNDING National Institute for Health Research Efficacy and Mechanism Evaluation.
PICO Summary
Population
Patients aged 16 years old or older with trauma-related haemorrhagic shock enrolled in the resuscitation with pre-hospital blood products (RePHILL) trial, based across four UK prehospital critical care services (n= 432).
Intervention
Packed red blood cells and lyophilised plasma (PRBC-LyoPlas, n= 209).
Comparison
Sodium chloride (n= 223).
Outcome
The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. The composite primary outcome occurred in 128 (64%) of 199 patients receiving PRBC-LyoPlas and 136 (65%) of 210 receiving sodium chloride. The rates of transfusion-related complications in the first 24 hours after emergency department arrival were similar (PRBC-LyoPlas eleven (7%) of 148 compared with sodium chloride nine (7%) of 137). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in the sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the sodium chloride group (abnormal liver function test). There were no treatment-related deaths.
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Systematic review of the efficacy of a hybrid operating theatre in the management of severe trauma
Khoo CY, Liew TYS, Mathur S
World journal of emergency surgery : WJES. 2021;16(1):43
Abstract
BACKGROUND Hybrid operating theatres (OT) allow for simultaneous interventional radiology and operative procedures, serving as a one-stop facility for the treatment of severely injured patients. Several countries have adopted the use of the hybrid OT however their clinical impact in improving efficiency and quality of care remains unclear. This study systematically reviews the clinical impact of the hybrid OT for treatment of the severely injured. METHODS A literature review of the PubMed, Embase and Cochrane databases was performed to identify all published articles in English, from 1st January 2000 to 31st December 2020, reporting on the impact of a hybrid OT for severe trauma. Articles were also reviewed for references of interest. RESULTS Five studies reporting the clinical impact of the hybrid OT, in a total of 951 patients, were shortlisted. All were cohort studies that compared patient outcomes in the hybrid OT versus a conventional group. Out of 3 studies that assessed timeliness to intervention, one reported shorter time associated with the hybrid OT, while the other two reported no difference. Mortality outcomes were reported in 4 studies and showed no significant difference associated with treatment in the hybrid OT. Two studies revealed shorter total procedure times associated with the hybrid OT. Two out of 3 studies that evaluated blood transfusion requirements reported decreased transfusion rates in the hybrid OT group. Only 1 study examined complication rates and demonstrated morbidity benefits associated with the hybrid OT. CONCLUSION Establishment of a hybrid OT requires a significant capital investment as well as a highly functioning multi-disciplinary team. The cost-benefit ratio remains unclear. Future studies, preferably in the form of clinical trials, are required to evaluate its usefulness in improving timeliness to definitive haemorrhage control and outcomes in severe trauma.
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Dose-dependent association between blood transfusion and nosocomial infections in trauma patients: A secondary analysis of patients from the PAMPer trial
Ladhani, H. A., Ho, V. P., Charbonnet, C. C., Sperry, J. L., Guyette, F. X., Brown, J. B., Daley, B. J., Miller, R. S., Harbrecht, B. G., Phelan, H. A., et al
The Journal of Trauma and Acute Care Surgery. 2021;91(2):272-278
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BACKGROUND The Prehospital Air Medical Plasma (PAMPer) trial demonstrated a survival benefit to trauma patients who received thawed plasma as part of early resuscitation. The objective of our study was to examine the association between blood transfusion and nosocomial infections among trauma patients who participated in the PAMPer trial. We hypothesized that transfusion of blood products will be associated with the development of nosocomial infections in a dose-dependent fashion. METHODS We performed a secondary analysis of prospectively collected data of patients in the PAMPer trial with hospital length of stay of at least 3 days. Demographics, injury characteristics, and number of blood products transfused were obtained to evaluate outcomes. Bivariate analysis was performed to identify differences between patients with and without nosocomial infections. Two logistic regression models were created to evaluate the association between nosocomial infections and (1) any transfusion of blood products, and (2) quantity of blood products. Both models were adjusted for age, sex, and Injury Severity Score. RESULTS A total of 399 patients were included: age, 46 years (interquartile range, 29-59 years); Injury Severity Score, 22 (interquartile range, 12-29); 73% male; 80% blunt mechanism; and 40 (10%) deaths. Ninety-three (27%) developed nosocomial infections, including pneumonia (n = 67), bloodstream infections (n = 14), catheter-associated urinary tract infection (n = 10), skin and soft tissue infection (n = 8), Clostridium difficile colitis (n = 7), empyema (n = 6), and complicated intra-abdominal infections (n = 3). Nearly 80% (n = 307) of patients received packed red blood cells (PRBCs); 12% received cryoprecipitate, 69% received plasma, and 27% received platelets. Patients who received any PRBCs had more than a twofold increase in nosocomial infections (odds ratio, 2.15; 95% confidence interval, 1.01-4.58; p = 0.047). The number of PRBCs given was also associated with the development of nosocomial infection (odds ratio, 1.10; 95% confidence interval, 1.05-1.16; p < 0.001). CONCLUSION Trauma patients in the PAMPer trial who received a transfusion of at least 1 U of PRBCs incurred a twofold increased risk of nosocomial infection, and the risk of infection was dose dependent. LEVEL OF EVIDENCE Therapeutic/care management, level IV.
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Pre-hospital transfusion of red blood cells. Part 1: A scoping review of current practice and transfusion triggers
van Turenhout, E. C., Bossers, S. M., Loer, S. A., Giannakopoulos, G. F., Schwarte, L. A., Schober, P.
Transfusion Medicine (Oxford, England). 2020;30(2):86-105
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Abstract
OBJECTIVES The primary aim of this scoping review is to describe the current use of pre-hospital transfusion of red blood cells (PHTRBC) and to evaluate criteria used to initiate PHTRBC. The effects on patients' outcomes will be reviewed in Part 2. BACKGROUND Haemorrhage is a preventable cause of death in trauma patients, and transfusion of red blood cells is increasingly used by Emergency Medical Services (EMS) for damage control resuscitation. However, there are no guidelines and little consensus on when to initiate PHTRBC. METHODS PubMed and Web of Science were searched through January 2019; 71 articles were included. RESULTS Transfusion triggers vary widely and involve vital signs, clinical signs of poor tissue perfusion, point of care measurements and pre-hospital ultrasound imaging. In particular, hypotension (most often defined as systolic blood pressure ≤ 90 mmHg), tachycardia (most often defined as heart rate ≥ 120/min), clinical signs of poor perfusion (eg, prolonged capillary refill time or changes in mental status) and injury type (ie, penetrating wounds) are common pre-hospital transfusion triggers. CONCLUSIONS PHTRBC is increasingly used by Emergency Medical Services, but guidelines on when to initiate transfusion are lacking. We identified the most commonly used transfusion criteria, and these findings may provide the basis for consensus-based pre-hospital transfusion protocols.
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The effect of massive transfusion protocol implementation on the survival of trauma patients: a systematic review and meta-analysis
Consunji R, Elseed A, El-Menyar A, Sathian B, Rizoli S, Al-Thani H, Peralta R
Blood transfusion = Trasfusione del sangue. 2020
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Editor's Choice
Abstract
BACKGROUND Massive transfusion protocol (MTP) has been widely adopted for the care of bleeding trauma patients but its actual effectiveness is unclear. An earlier meta-analysis on the implementation of MTP for injured patients from 1990 to 2013 reported that only 2 out of 8 studies showed statistical improvement in survival. This study aimed to conduct an updated systematic review and meta-analysis to evaluate the effect of implementing an MTP on the mortality of trauma patients. MATERIALS AND METHODS MEDLINE, PubMed, Cochrane Library and Google scholar databases were systematically searched for relevant studies published from 1(st) January 2008 to 30(th) September 2019 using a combination of keywords and additional manual searching of reference lists. Inclusion criteria were: original study in English, study population including trauma patients, and comparison of mortality outcomes before and after institutional implementation of an MTP. Primary outcomes were 24-hour, 30-day, and overall mortality. RESULTS Fourteen studies met inclusion criteria, analysing outcomes from 3,201 trauma patients. There was a wide range of outcomes, patient populations, and process indicators utilised by the different authors. MTP significantly reduced the overall mortality for trauma patients (OR 0.71 [0.56-0.90]). No significant reduction was seen in either the 24-hour mortality (OR 0.81 [0.57-1.14]) or the 30-day mortality (OR 0.73 [0.46-1.16]). However, when mortality timing was unspecified, mortality was statistically reduced (OR 0.69 [0.55-0.86]). DISCUSSION The present study found a significant reduction in mortality following MTP implementation and thus it should be recommended to all institutions managing acutely injured patients. To better identify which elements of an MTP contribute to this effect, we encourage the use of standard nomenclature, indicators, protocols and patient populations in all future MTP studies.
PICO Summary
Population
Trauma patients (14 studies, n= 3201).
Intervention
Implementation of a massive transfusion protocol (MTP) on the mortality of trauma patients.
Comparison
Outcome
There was a wide range of outcomes, patient populations, and process indicators utilised by the different authors. MTP significantly reduced the overall mortality for trauma patients. No significant reduction was seen in either the 24-hour mortality or the 30-day mortality. However, when mortality timing was unspecified, mortality was statistically reduced.
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Dynamic Impact of Transfusion Ratios on Outcomes in Severely Injured Patients: Targeted Machine Learning Analysis of the PROPPR Randomized Clinical Trial
Nguyen M, Pirracchio R, Kornblith LZ, Callcut R, Fox EE, Wade CE, Schreiber M, Holcomb JB, Coyle J, Cohen M, et al
J Trauma Acute Care Surg. 2020
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Abstract
BACKGROUND Massive transfusion protocols to treat post-injury hemorrhage are based on pre-defined blood product transfusion ratios followed by goal-directed transfusion based on patient's clinical evolution. However, it remains unclear how these transfusion ratios impact patient outcomes over time from injury. METHODS The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) is a phase 3, randomized controlled trial, across 12 level-I trauma centers in North America. From 2012 to 2013, 680 severely injured patients required massive transfusion. We used semi-parametric machine learning techniques and causal inference methods to augment the intent-to-treat analysis of PROPPR, estimating the dynamic relationship between transfusion ratios and outcomes: mortality and hemostasis at different time-points during the first 24 hours after admission. RESULTS In the intention-to-treat analysis, the 1:1:1 group tended to have decreased mortality, but with no statistical significance. For patients in whom hemostasis took longer than 2 hours, the 1:1:1 ratio was associated with a higher probability of hemostasis, statistically significant from the 4 hour on. In the per-protocol, actual-transfusion-ratios-received analysis, during four successive time intervals, no significant association was found between the actual ratios and mortality. When comparing patient groups who received both high plasma:PRBC and high platelet:PRBC ratios to the group of low ratios in both, the relative risk of achieving hemostasis was 2.49 (95% CI = 1.19-5.22) during the 3 hour after admission, suggesting a significant beneficial impact of higher transfusion ratios of plasma and platelets on hemostasis. CONCLUSIONS Our results suggest that the impact of transfusion ratios on hemostasis is dynamic. Overall, the transfusion ratios had no significant impact on mortality over time. However, receiving higher ratios of platelets and plasma relative to red blood cells hastens hemostasis in subjects who have yet to achieve hemostasis within 3 hours after hospital admission. LEVEL OF EVIDENCE Prognostic, level III.
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Sex-based differences in transfusion need after severe injury: Findings of the PROPPR study
McCrum ML, Leroux B, Fang T, Bulger E, Arbabi S, Wade CE, Fox E, Holcomb JB, Robinson B
Surgery. 2019
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BACKGROUND Women are underrepresented in trauma research, and aggregated results of clinical trials may mask effects that differ by sex. It is unclear whether women respond differently to severe hemorrhage compared with men. We sought to evaluate sex-based differences in outcomes after severe trauma with hemorrhage. METHODS We performed a secondary analysis of the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial. Trauma patients predicted to require massive transfusion were randomized to a 1:1:1 vs 1:1:2 plasma to platelet to red blood cell transfusion ratio. Analysis was performed according to sex, controlling for clinical characteristics and transfusion arm. RESULTS A total of 134 women and 546 men were analyzed. In multivariable analysis, there was no difference in mortality at 24 hours (hazard ratio for women 0.64, 95% confidence interval 0.34-1.23, P = .18) or in time to hemostasis (hazard ratio 1.10, 95% confidence interval 0.84-1.42, P = .49) by sex. We observed no difference between sexes in volume of blood products transfused during active hemorrhage. However, after anatomic hemostasis, women received lower volumes of all products, with a 38% reduction in fresh frozen plasma (mean ratio 0.62 (95% confidence interval 0.43-0.89, P = .01), 49% reduction in platelets (mean ratio 0.51, 95% confidence interval 0.33-0.79, P < .01) and 49% reduction in volume of red blood cells (mean ratio 0.51, 95% confidence interval 0.33-0.79, P < .01). CONCLUSION Mortality and time to hemostasis of trauma patients with hemorrhage did not differ by sex. Although there was no difference in transfusion requirement during active hemorrhage, once hemostasis was achieved, women received fewer units of all blood products than men. Further research is required to determine whether women exhibit differences in coagulation during and after severe traumatic hemorrhage.