Whole Blood and Blood Component Resuscitation in Trauma: Interaction and Association with Mortality.

OBJECTIVE: Evaluate the interaction between whole blood (WB) and blood component resuscitation in relation to mortality following trauma. SUMMARY BACKGROUND DATA: WB is increasingly available in civilian trauma resuscitation, and it is typically transfused concomitantly with blood components. The interaction between WB and blood component transfusions is unclear. METHODS: Adult trauma patients with a shock index >1 who received ≥4 combined units of red blood cells (RBC) or WB within 4 hours across 501 United States trauma centers were included using the American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) database. The associations between 1)WB resuscitation and mortality, 2)WB to total transfusion volume ratio (WB:TTV) and mortality, 3)balanced blood component transfusion in the setting of combined WB and component resuscitation and mortality were evaluated with multivariable analysis. RESULTS: A total of 12,275 patients were included (WB: 2,884 vs. component-only: 9,391). WB resuscitation was associated with lower odds of 4-hour (adjusted odds ratio [aOR]: 0.81 [0.68-0.97]), 24-hour, and 30-day mortality compared to component-only. Higher WB:TTV ratios were significantly associated with lower 4-hour, 24-hour, and 30-day mortality, with a 13% decrease in odds of 4-hour mortality for each 10% increase in the WB:TTV ratio (0.87 [95%CI:0.80 - 0.94]). Balanced blood component transfusion was associated with significantly lower odds of 4-hour (aOR: 0.45 [95%CI: 0.29 - 0.68]), 24-hour, and 30-day mortality in the setting of combined WB and blood component resuscitation. CONCLUSIONS: WB resuscitation, higher WB:TTV ratios, and balanced blood component transfusion in conjunction with WB were associated with lower mortality in trauma patients presenting in shock requiring 4 units of RBC and/or WB transfusion within 4 hours of arrival.

Association Between Emergency Medical Service Agency Volume and Mortality in Trauma Patients.

OBJECTIVE: The aim of this study was to evaluate the association of annual trauma patient volume on outcomes for emergency medical services (EMS) agencies. BACKGROUND: Regionalization of trauma care saves lives. The underlying concept driving this is a volume-outcome relationship. EMS are the entry point to the trauma system, yet it is unknown if a volume-outcome relationship exists for EMS. METHODS: A retrospective analysis of prospective cohort including 8 trauma centers and 20 EMS air medical and metropolitan ground transport agencies. Patients 18 to 90 years old with injury severity scores ≥9 transported from the scene were included. Patient and agency-level risk-adjusted regression determined the association between EMS agency trauma patient volume and early mortality. RESULTS: A total of 33,511 were included with a median EMS agency volume of 374 patients annually (interquartile range: 90-580). Each 50-patient increase in EMS agency volume was associated with 5% decreased odds of 6-hour mortality (adjusted odds ratio=0.95; 95% CI: 0.92-0.99, P =0.03) and 3% decreased odds of 24-hour mortality (adjusted odds ratio=0.97; 95% CI: 0.95-0.99, P =0.04). Prespecified subgroup analysis showed EMS agency volume was associated with reduced odds of mortality for patients with prehospital shock, requiring prehospital airway placement, undergoing air medical transport, and those with traumatic brain injury. Agency-level analysis demonstrated that high-volume (>374 patients/year) EMS agencies had a significantly lower risk-standardized 6-hour mortality rate than low-volume (<374 patients/year) EMS agencies (1.9% vs 4.8%, P <0.01). CONCLUSIONS: A higher volume of trauma patients transported at the EMS agency level is associated with improved early mortality. Further investigation of this volume-outcome relationship is necessary to leverage quality improvement, benchmarking, and educational initiatives.

Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock. BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667468.

Early Glasgow Coma Scale Score and Prediction of Traumatic Brain Injury: A Secondary Analysis of Three Harmonized Prehospital Randomized Clinical Trials.

OBJECTIVES: The prehospital prediction of the radiographic diagnosis of traumatic brain injury (TBI) in hemorrhagic shock patients has the potential to promote early therapeutic interventions. However, the identification of TBI is often challenging and prehospital tools remain limited. While the Glasgow Coma Scale (GCS) score is frequently used to assess the extent of impaired consciousness after injury, the utility of the GCS scores in the early prehospital phase of care to predict TBI in patients with severe injury and concomitant shock is poorly understood.METHODS: We performed a post-hoc, secondary analysis utilizing data derived from three randomized prehospital clinical trials: the Prehospital Air Medical Plasma trial (PAMPER), the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport trial (STAAMP), and the Pragmatic Prehospital Type O Whole Blood Early Resuscitation (PPOWER) trial. Patients were dichotomized into two cohorts based on the presence of TBI and then further stratified into three groups based on prehospital GCS score: GCS 3, GCS 4-12, and GCS 13-15. The association between prehospital GCS score and clinical documentation of TBI was assessed.RESULTS: A total of 1,490 enrolled patients were included in this analysis. The percentage of patients with documented TBI in those with a GCS 3 was 59.5%, 42.4% in those with a GCS 4-12, and 11.8% in those with a GCS 13-15. The positive predictive value (PPV) of the prehospital GCS score for the diagnosis of TBI is low, with a GCS of 3 having only a 60% PPV. Hypotension and prehospital intubation are independent predictors of a low prehospital GCS. Decreasing prehospital GCS is strongly associated with higher incidence or mortality over time, irrespective of the diagnosis of TBI.CONCLUSIONS: The ability to accurately predict the presence of TBI in the prehospital phase of care is essential. The utility of the GCS scores in the early prehospital phase of care to predict TBI in patients with severe injury and concomitant shock is limited. The use of novel scoring systems and improved technology are needed to promote the accurate early diagnosis of TBI.

Prehospital Time Following Traumatic Injury Is Independently Associated With the Need for In-Hospital Blood and Early Mortality for Specific Injury Types.

OBJECTIVE: Treating traumatic hemorrhage is time sensitive. Prehospital care and transport modes (eg, helicopter and ground) may influence in-hospital events. We hypothesized that prehospital time (on-scene time [OST] and total prehospital time [TPT]) and transport mode are associated with same-day transfusion and mortality. Furthermore, we sought to identify regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. METHODS: We obtained prehospital, in-hospital, and trauma registry data from an 8-center cohort of adult nonburn trauma patients from 2017 to 2022 directly transported from the scene to the hospital and having an Injury Severity Score (ISS) > 9 for the Task Order 1 project of the Linking Investigators in Trauma and Emergency Services research network. We excluded patients missing prehospital times, patients < 18 years of age, patients from interfacility transfers, and recipients of prehospital blood. Our same-day outcomes were in-hospital transfusions within 4 hours and 24-hour mortality. Each outcome was adjusted using multivariable logistic regression for covariates of prehospital phases (OST and TPT), mode of transport (helicopter and ground), age, sex, ISS, Glasgow Coma Scale motor subscale score < 6, and field hypotension (systolic blood pressure < 90 mm Hg). We evaluated the association of prehospital time on outcomes for scene missions by transport mode across severe injury patterns defined by Abbreviated Injury Scale > 2 body regions. RESULTS: Of 78,198 subjects, 34,504 were eligible for the study with a mean age of 47.6 ± 20.3 years, ISS of 18 ± 11, OST of 15.9 ± 9.5 minutes, and TPT of 48.7 ± 20.3 minutes. Adjusted for injury severity and demographic factors, transport type significantly modified the relationship between prehospital time and outcomes. The association of OST and TPT with the odds of 4-hour transfusion was absent for the ground emergency medical services (GEMS) cohort and present for the helicopter emergency medical services (HEMS) ambulance cohort, whereas these times were associated with decreased 24-hour mortality for both transport types. When stratifying by injury to most anatomic regions, OST and TPT were associated with a decreased need for 4-hour transfusions in the GEMS cohort. However, OST was associated with increased early transfusion only among patients with severe injuries of the thorax, and this association persisted after adjusting additionally for injury type (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.00-1.05; P = .02). The presence of polytrauma supported an association between prehospital time and decreased 24-hour mortality for the GEMS cohort (OST: OR = 0.97; 95% CI, 0.95-0.99; P < .01; TPT: OR = 0.99; 95% CI, 0.98-0.99; P = .02), whereas no injuries showed significant association of helicopter prehospital time on mortality after adjustment. CONCLUSION: We determined that transport type affects the relationship between prehospital time and hospital outcomes (4-hour transfusion: positive relationship for HEMS and negative for GEMS, 24-hour mortality: negative for both transport types). Furthermore, we identified regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. Of these regions, most notable were severe isolated injuries to the thorax that supported a positive relationship between HEMS OST and 4-hour transfusions and polytrauma that showed a negative relationship between GEMS OST or TPT and 24-hour mortality after adjustment.

Direct Trauma Center Access by Helicopter Emergency Medical Services is Associated With Improved Survival After Severe Injury.

OBJECTIVE: Evaluate the association of survival with helicopter transport directly to a trauma center compared with ground transport to a non-trauma center (NTC) and subsequent transfer. SUMMARY BACKGROUND DATA: Helicopter transport improves survival after injury. One potential mechanism is direct transport to a trauma center when the patient would otherwise be transported to an NTC for subsequent transfer. METHODS: Scene patients 16 years and above with positive physiological or anatomic triage criteria within PTOS 2000-2017 were included. Patients transported directly to level I/II trauma centers by helicopter were compared with patients initially transported to an NTC by ground with a subsequent helicopter transfer to a level I/II trauma center. Propensity score matching was used to evaluate the association between direct helicopter transport and survival. Individual triage criteria were evaluated to identify patients most likely to benefit from direct helicopter transport. RESULTS: In all, 36,830 patients were included. Direct helicopter transport was associated with a nearly 2-fold increase in odds of survival compared with NTC ground transport and subsequent transfer by helicopter (aOR 2.78; 95% CI 2.24-3.44, P <0.01). Triage criteria identifying patients with a survival benefit from direct helicopter transport included GCS≤13 (1.71; 1.22-2.41, P <0.01), hypotension (2.56; 1.39-4.71, P <0.01), abnormal respiratory rate (2.30; 1.36-3.89, P <0.01), paralysis (8.01; 2.03-31.69, P <0.01), hemothorax/pneumothorax (2.34; 1.36-4.05, P <0.01), and multisystem trauma (2.29; 1.08-4.84, P =0.03). CONCLUSIONS: Direct trauma center access is a mechanism driving the survival benefit of helicopter transport. First responders should consider helicopter transport for patients meeting these criteria who would otherwise be transported to an NTC.

Low Titer Group O Whole Blood In Injured Children Requiring Massive Transfusion.

OBJECTIVE: The aim of this study was to assess the survival impact of low-titer group O whole blood (LTOWB) in injured pediatric patients who require massive transfusion. SUMMARY BACKGROUND DATA: Limited data are available regarding the effectiveness of LTOWB in pediatric trauma. METHODS: A prospective observational study of children requiring massive transfusion after injury at UPMC Children's Hospital of Pittsburgh, an urban academic pediatric Level 1 trauma center. Injured children ages 1 to 17 years who received a total of >40 mL/kg of LTOWB and/or conventional components over the 24 hours after admission were included. Patient characteristics, blood product utilization and clinical outcomes were analyzed using Kaplan-Meier survival curves, log rank tests and Cox proportional hazards regression analyses. The primary outcome was 28-day survival. RESULTS: Of patients analyzed, 27 of 80 (33%) received LTOWB as part of their hemostatic resuscitation. The LTOWB group was comparable to the component therapy group on baseline demographic and physiologic parameters except older age, higher body weight, and lower red blood cell and plasma transfusion volumes. After adjusting for age, total blood product volume transfused in 24 hours, admission base deficit, international normalized ratio (INR), and injury severity score (ISS), children who received LTOWB as part of their resuscitation had significantly improved survival at both 72 hours and 28 days post-trauma [adjusted odds ratio (AOR) 0.23, P = 0.009 and AOR 0.41, P = 0.02, respectively]; 6-hour survival was not statistically significant (AOR = 0.51, P = 0.30). Survivors at 28 days in the LTOWB group had reduced hospital LOS, ICU LOS, and ventilator days compared to the CT group. CONCLUSION: Administration of LTOWB during the hemostatic resuscitation of injured children requiring massive transfusion was independently associated with improved 72-hour and 28-day survival.

Timing of RhD-positive red blood cell administration is associated with D-alloimmunization in injured patients.

BACKGROUND: The D-alloimmunization rate in trauma patients does not appear to depend on the number of RhD-positive units transfused. The effect of the timing and pattern of RhD-positive transfusions has not been evaluated. METHODS: RhD-negative trauma patients who were transfused with RhD-positive red blood cells (RBC) or low titer group O whole blood (collectively called RBCs) on at least two separate calendar days and who had antibody detection tests performed at least 14 days after the second RhD-positive RBC transfusion without receiving RhIg were included in the analysis. Patients whose anti-D was detected within 14 days of the index RhD-positive RBC transfusion were excluded. Patient demographics and the dates of RhD-positive RBC transfusions and results of antibody detection tests performed after the index transfusion were collected on eligible patients. RESULTS: There were 44/61 (72.1%) patients in whom anti-D was not detected (non-alloimmunized) and 17/61 (27.9%) in whom anti-D was detected (alloimmunized). The patients had similar demographics with trends towards higher median admission heart rates and lower median admission Glasgow Coma Scale values in the alloimmunized group. Both groups received statistically identical median quantities of RhD-positive RBCs (non-alloimmunized 5 vs. alloimmunized 4 units, p = .53), however, the alloimmunized group received all their RhD-positive RBCs over a significantly shorter period of time compared to the non-alloimmunized (median 4 vs. 15 days, respectively, p = .01). CONCLUSION: Receipt of all RhD-positive RBCs over a shorter period of time was associated with higher D-alloimmunization rates. These results need to be confirmed in larger studies.

Transfusion of ABO-group identical red blood cells following uncrossmatched transfusion does not lead to higher mortality in civilian trauma patients.

BACKGROUND: Questions persist about the safety of switching non-group O recipients of group O uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) to ABO-identical RBCs during their resuscitation. METHODS: The database of an earlier nine-center study of transfusing incompatible plasma to trauma patients was reanalyzed. The patients were divided into three groups based on 24-h RBC transfusion: (1) group O patients who received group O RBC/LTOWB units (control group, n = 1203), (2) non-group O recipients who received only group O units (n = 646), (3) non-group O recipients who received at least one unit of group O and non-group O units (n = 562). Fixed marginal effect of receipt of non-O RBC units on 6- and 24-h and 30-day mortality was calculated. RESULTS: The non-O patients who received only group O RBCs received fewer RBC/LTOWB units and had slightly but significantly lower injury severity score compared to control group; non-group O patients who received both group O and non-O units received significantly more RBC/LTOWB units and had a slightly but significantly higher injury severity score compared to control group. In the multivariate analysis, the non-O patients who received only group O RBCs had significantly higher mortality at 6-h compared to the controls; the non-group O recipients of O and non-O RBCs did not demonstrate higher mortality. At 24-h and 30-days, there were no differences in survival between the groups. CONCLUSION: Providing non-group O RBCs to non-group O trauma patients who also received group O RBC units is not associated with higher mortality.

The Geography of Injuries in Trauma Systems: Using Home as a Proxy for Incident Location.

INTRODUCTION: Effective trauma system organization is crucial to timely access to care and requires accurate understanding of injury and resource locations. Many systems rely on home zip codes to evaluate geographic distribution of injury; however, few studies have evaluated the reliability of home as a proxy for incident location after injury. METHODS: We analyzed data from a multicenter prospective cohort collected from 2017 to 2021. Injured patients with both home and incident zip codes were included. Outcomes included discordance and differential distance between home and incident zip code. Associations of discordance with patient characteristics were determined by logistic regression. We also assessed trauma center catchment areas based on home versus incident zip codes and variation regionally at each center. RESULTS: Fifty thousand one hundred seventy-five patients were included in the analysis. Home and incident zip codes were discordant in 21,635 patients (43.1%). Injuries related to motor vehicles (aOR: 4.76 [95% CI 4.50-5.04]) and younger adults 16-64 (aOR: 2.46 [95% CI 2.28-2.65]) were most likely to be discordant. Additionally, as injury severity score increased, discordance increased. Trauma center catchment area differed up to two-thirds of zip codes when using home versus incident location. Discordance rate, discordant distance, and catchment area overlap between home and incident zip codes all varied significantly by geographic region. CONCLUSIONS: Home location as proxy for injury location should be used with caution and may impact trauma system planning and policy, especially in certain populations. More accurate geolocation data are warranted to further optimize trauma system design.

High Dimensional Multiomics Reveals Unique Characteristics of Early Plasma Administration in Polytrauma Patients With TBI.

OBJECTIVES: The authors sought to identify causal factors that explain the selective benefit of prehospital administration of thawed plasma (TP) in traumatic brain injury (TBI) patients using mediation analysis of a multiomic database. BACKGROUND: The Prehospital Air Medical Plasma (PAMPer) Trial showed that patients with TBI and a pronounced systemic response to injury [defined as endotype 2 (E2)], have a survival benefit from prehospital administration of TP. An interrogation of high dimensional proteomics, lipidomics and metabolomics previously demonstrated unique patterns in circulating biomarkers in patients receiving prehospital TP, suggesting that a deeper analysis could reveal causal features specific to TBI patients. METHODS: A novel proteomic database (SomaLogic Inc., aptamer-based assay, 7K platform) was generated using admission blood samples from a subset of patients (n=149) from the PAMPer Trial. This proteomic dataset was combined with previously reported metabolomic and lipidomic datasets from these same patients. A 2-step analysis was performed to identify factors that promote survival in E2-TBI patients who had received early TP. First, features were selected using both linear and multivariate-latent-factor regression analyses. Then, the selected features were entered into the causal mediation analysis. RESULTS: Causal mediation analysis of observable features identified 16 proteins and 41 lipids with a high proportion of mediated effect (>50%) to explain the survival benefit of early TP in E2-TBI patients. The multivariate latent-factor regression analyses also uncovered 5 latent clusters of features with a proportion effect >30%, many in common with the observable features. Among the observable and latent features were protease inhibitors known to inhibit activated protein C and block fibrinolysis (SERPINA5 and CPB2), a clotting factor (factor XI), as well as proteins involved in lipid transport and metabolism (APOE3 and sPLA(2)-XIIA). CONCLUSIONS: These findings suggest that severely injured patients with TBI process exogenous plasma differently than those without TBI. The beneficial effects of early TP in E2-TBI patients may be the result of improved blood clotting and the effect of brain protective factors independent of coagulation.

Receipt of at least 4 units of low titer group O whole blood with titer <100 does not lead to hemolysis in adult trauma patients.

BACKGROUND: The serological safety of transfusing low titer group O whole blood (LTOWB) with an anti-A and anti-B titer of <100 was evaluated in group O and non-group O trauma recipients. METHODS: Civilian adult trauma patients who received ≥4 units of leukoreduced LTOWB during their initial resuscitation and who survived for >24 h after admission at two level 1 trauma centers were included in this retrospective study. Lactate dehydrogenase (LDH), total bilirubin, haptoglobin, potassium, creatinine were evaluated on the day of LTOWB transfusion (day 0) and on the next 3 days. RESULTS: There were 77 injured recipients evaluated: 39 non-group O and 38 group O. The median (IQR) number of transfused LTOWB units was 4 (4-6) and 4 (4-5), respectively, and the maximum number of units was 8 and 11, respectively. The non-group O patients received a median (IQR) volume of 1710 ml (1368-2070) of ABO-incompatible plasma. Comparing non-group O to group O recipients, there were no significant differences in the median haptoglobin, LDH, or creatinine concentrations at any time point. The median concentration of total bilirubin was significantly higher amongst the non-group O recipients on days 1 and 2, while on day 0 the median potassium concentration was significantly higher amongst the group O recipients. All median elevated values were within the laboratory's normal range. Amongst the non-group O recipients there were no reported transfusion reactions. CONCLUSION: Receiving at least four LTOWB units (anti-A&B titer <100) was not associated with biochemical/clinical evidence of hemolysis in adult trauma patients.

Accuracy of Risk Estimation for Surgeons Versus Risk Calculators in Emergency General Surgery.

INTRODUCTION: Surgical risk calculators have expanded in both number and sophistication of their predictive approach. These calculators are gaining popularity as validated tools to help surgeons estimate mortality and complications following emergency general surgery (EGS). However, the accuracy of risk estimates generated by these calculators compared to risk estimation by practicing surgeons has not been explored. METHODS: Acute care surgeons at a quaternary care center prospectively estimated 30-d mortality and complications for adult EGS patients (2019-2021). Surgeon predictions were compared to Predictive OpTimal Trees in Emergency Surgery Risk (POTTER) and NSQIP estimates. Observed-to-expected (O:E) ratios of median aggregate estimates were calculated. C-statistics for surgeon and calculator estimations were utilized to quantify predictive accuracy. RESULTS: Among 150 patients (median 61 y, 45% male), 30-d mortality was 15% (n = 23). Observed rates of prolonged mechanical ventilation and acute renal failures were 30% and 10%, respectively. Overall, surgeon predictions were similar to risk calculator estimates for mortality (c-statistics 0.843 [surgeon] versus 0.848 [POTTER] and 0.815 [NSQIP]) and need for prolonged ventilation (c-statistics 0.801 versus 0.722 and 0.689, respectively). Surgeons tended to overestimate complication risks. Surgeon experience was not significantly associated with mortality prediction in an adjusted model. CONCLUSIONS: Acute care surgeons at a quaternary care center predicted postoperative mortality and complications with similar discrimination when compared to surgical risk calculators. Surgeon expertise should be utilized in conjunction with risk calculators when counseling EGS patients regarding anticipated postoperative outcomes. Surgeons should be cognizant of patterns in overestimation or underestimation of complications.

THOR-AABB Working Party Recommendations for a Prehospital Blood Product Transfusion Program.

The evidence for the lifesaving benefits of prehospital transfusions is increasing. As such, emergency medical services (EMS) might increasingly become interested in providing this important intervention. While a few EMS and air medical agencies have been providing exclusively red blood cell (RBC) transfusions to their patients for many years, transfusing plasma in addition to the RBCs, or simply using low titer group O whole blood (LTOWB) in place of two separate components, will be a novel experience for many services. The recommendations presented in this document were created by the Trauma, Hemostasis and Oxygenation Research (THOR)-AABB (formerly known as the American Association of Blood Banks) Working Party, and they are intended to provide a framework for implementing prehospital blood transfusion programs in line with the best available evidence. These recommendations cover all aspects of such a program including storing, transporting, and transfusing blood products in the prehospital phase of hemorrhagic resuscitation.

Early Prehospital Tranexamic Acid Following Injury Is Associated With a 30-day Survival Benefit: A Secondary Analysis of a Randomized Clinical Trial.

OBJECTIVE: We sought to characterize the timing of administration of prehospital tranexamic acid (TXA) and associated outcome benefits. BACKGROUND: TXA has been shown to be safe in the prehospital setting post-injury. METHODS: We performed a secondary analysis of a recent prehospital randomized TXA clinical trial in injured patients. Those who received prehospital TXA within 1 hour (EARLY) from time of injury were compared to those who received prehospital TXA beyond 1 hour (DELAYED). We included patients with a shock index of >0.9. Primary outcome was 30-day mortality. Kaplan-Meier and Cox Hazard regression were utilized to characterize mortality relationships. RESULTS: EARLY and DELAYED patients had similar demographics, injury characteristics, and shock severity but DELAYED patients had greater prehospital resuscitation requirements and longer prehospital times. Stratified Kaplan-Meier analysis demonstrated significant separation for EARLY patients (N = 238, log-rank chi-square test, 4.99; P = 0.03) with no separation for DELAYED patients (N = 238, log-rank chi-square test, 0.04; P = 0.83). Stratified Cox Hazard regression verified, after controlling for confounders, that EARLY TXA was associated with a 65% lower independent hazard for 30-day mortality [hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.19-0.65, P = 0.001] with no independent survival benefit found in DELAYED patients (HR 1.00, 95% CI 0.63-1.60, P = 0.999). EARLY TXA patients had lower incidence of multiple organ failure and 6-hour and 24-hour transfusion requirements compared to placebo. CONCLUSIONS: Administration of prehospital TXA within 1 hour from injury in patients at risk of hemorrhage is associated with 30-day survival benefit, lower incidence of multiple organ failure, and lower transfusion requirements.

Prehospital Blood Product and Crystalloid Resuscitation in the Severely Injured Patient: A Secondary Analysis of the Prehospital Air Medical Plasma Trial.

OBJECTIVE: The aim of this study was to determine whether prehospital blood products reduce 30-day mortality in patients at risk for hemorrhagic shock compared with crystalloid only resuscitation. SUMMARY OF BACKGROUND DATA: Hemorrhage is the primary cause of preventable death after injury. Large volume crystalloid resuscitation can be deleterious. The benefits of prehospital packed red blood cells (PRBCs), plasma, or transfusion of both products among trauma patients is unknown compared with crystalloid. METHODS: Secondary analysis of the multicenter PAMPer trial was performed on hypotensive injured patients from the scene. The trial randomized 27 helicopter bases to prehospital plasma or standard resuscitation. Standard resuscitation at the sites was equally divided between crystalloid and crystalloid + PRBC. This led to 4 prehospital resuscitation groups: crystalloid only; PRBC; plasma; and PRBC+plasma. Cox regression determined the association between resuscitation groups and risk-adjusted 30-day mortality. The dose effect of resuscitation fluids was also explored. RESULTS: Four hundred seven patients were included. PRBC+plasma had the greatest benefit [hazard ratio (HR) 0.38; 95% confidence interval (95% CI) 0.26-0.55, P < 0.001], followed by plasma (HR 0.57; 95% CI 0.36-0.91, P = 0.017) and PRBC (HR 0.68; 95% CI 0.49-0.95, P = 0.025) versus crystalloid only. Mortality was lower per-unit of PRBC (HR 0.69; 95% CI 0.52-0.92, p = 0.009) and plasma (HR 0.68; 95% CI 0.54-0.88, P = 0.003). Crystalloid volume was associated with increased mortality among patients receiving blood products (HR 1.65; 95% CI 1.17-2.32, P = 0.004). CONCLUSION: Patients receiving prehospital PRBC+plasma had the greatest mortality benefit. Crystalloid only had the worst survival. Patients with hemorrhagic shock should receive prehospital blood products when available, preferably PRBC+plasma. Prehospital whole blood may be ideal in this population.

Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials.

OBJECTIVE: To address the clinical and regulatory challenges of optimal primary endpoints for bleeding patients by developing consensus-based recommendations for primary clinical outcomes for pivotal trials in patients within 6 categories of significant bleeding, (1) traumatic injury, (2) intracranial hemorrhage, (3) cardiac surgery, (4) gastrointestinal hemorrhage, (5) inherited bleeding disorders, and (6) hypoproliferative thrombocytopenia. BACKGROUND: A standardized primary outcome in clinical trials evaluating hemostatic products and strategies for the treatment of clinically significant bleeding will facilitate the conduct, interpretation, and translation into clinical practice of hemostasis research and support alignment among funders, investigators, clinicians, and regulators. METHODS: An international panel of experts was convened by the National Heart Lung and Blood Institute and the United States Department of Defense on September 23 and 24, 2019. For patients suffering hemorrhagic shock, the 26 trauma working-group members met for almost a year, utilizing biweekly phone conferences and then an in-person meeting, evaluating the strengths and weaknesses of previous high quality studies. The selection of the recommended primary outcome was guided by goals of patient-centeredness, expected or demonstrated sensitivity to beneficial treatment effects, biologic plausibility, clinical and logistical feasibility, and broad applicability. CONCLUSIONS: For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. Particular attention was recommended to injury and treatment time, as well as robust assessments of multiple safety related outcomes.

Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock.

BACKGROUND: After a person has been injured, prehospital administration of plasma in addition to the initiation of standard resuscitation procedures in the prehospital environment may reduce the risk of downstream complications from hemorrhage and shock. Data from large clinical trials are lacking to show either the efficacy or the risks associated with plasma transfusion in the prehospital setting. METHODS: To determine the efficacy and safety of prehospital administration of thawed plasma in injured patients who are at risk for hemorrhagic shock, we conducted a pragmatic, multicenter, cluster-randomized, phase 3 superiority trial that compared the administration of thawed plasma with standard-care resuscitation during air medical transport. The primary outcome was mortality at 30 days. RESULTS: A total of 501 patients were evaluated: 230 patients received plasma (plasma group) and 271 received standard-care resuscitation (standard-care group). Mortality at 30 days was significantly lower in the plasma group than in the standard-care group (23.2% vs. 33.0%; difference, -9.8 percentage points; 95% confidence interval, -18.6 to -1.0%; P=0.03). A similar treatment effect was observed across nine prespecified subgroups (heterogeneity chi-square test, 12.21; P=0.79). Kaplan-Meier curves showed an early separation of the two treatment groups that began 3 hours after randomization and persisted until 30 days after randomization (log-rank chi-square test, 5.70; P=0.02). The median prothrombin-time ratio was lower in the plasma group than in the standard-care group (1.2 [interquartile range, 1.1 to 1.4] vs. 1.3 [interquartile range, 1.1 to 1.6], P<0.001) after the patients' arrival at the trauma center. No significant differences between the two groups were noted with respect to multiorgan failure, acute lung injury-acute respiratory distress syndrome, nosocomial infections, or allergic or transfusion-related reactions. CONCLUSIONS: In injured patients at risk for hemorrhagic shock, the prehospital administration of thawed plasma was safe and resulted in lower 30-day mortality and a lower median prothrombin-time ratio than standard-care resuscitation. (Funded by the U.S. Army Medical Research and Materiel Command; PAMPer ClinicalTrials.gov number, NCT01818427 .).

Rate of RhD-alloimmunization after the transfusion of multiple RhD-positive primary red blood cell-containing products.

INTRODUCTION: Early transfusion reduces mortality in bleeding patients. In this setting, RhD-positive blood products might be transfused. This study determined the association between the RhD-alloimmunization rate and the number of RhD-positive products transfused. METHODS: RhD-negative patients between 13 and 50 years who were transfused with ≥1 RhD-positive red blood cell (RBC) or whole blood units between January 1, 2000 and December 31, 2019 in a healthcare network were identified. Study patients had to have had at least one antibody detection test performed ≥14 days after the index RhD-positive transfusion and not receive RhIg. Patients were stratified into groups that received 1, 2, 3-5, 6-10, 11-20, and >20 RhD-positive transfusions and the RhD-alloimmunization rate was determined for each group. RESULTS: There were 335 patients included; 52/335 (15.5%) were females. Overall, there were 117/335 (34.9%, CI: 29.8%-40.3%) recipients who became RhD-alloimmunized. There was no significant dosage effect in the RhD-alloimmunization rates as the exposure to RhD-positive units increased from one RhD-positive unit to more than 20 RhD-positive units (p = .270 for non-parametric trend test). In an exploratory analysis, patients who received 100% of their RhD-positive transfusions within 72 h of the index transfusion had a significantly higher rate of RhD-alloimmunization compared to those who were transfused over a longer period of time (42.3% vs. 21.4%, respectively; p = .001). CONCLUSION: These results suggest that there may not be an increased RhD-alloimmunization risk with transfusing multiple RhD-positive units after one RhD-positive unit has been transfused. These findings need confirmation in larger studies.

Injured recipients of low-titer group O whole blood have similar clinical outcomes compared to recipients of conventional component therapy: A single-center, retrospective study.

INTRODUCTION: Low-titer group O whole blood (LTOWB) is being increasingly transfused to injured patients. This study evaluated a range of clinical outcomes to determine if receipt of LTOWB predisposed recipients to worse outcomes compared to recipients of conventional component therapy (CCT). METHODS: A retrospective analysis of trauma patients who received at least 3 units of LTOWB (LTOWB group) versus those that received at least 3 units of RBCs, 1 unit of plasma and 1 unit of platelets but no LTOWB (CCT group) during the first 24 h of their admission was performed. Causal treatment effects were explored using propensity score matching (PSM) and coarsened exact matching (CEM). Important clinical outcomes were evaluated. RESULTS: There were 165 CCT and 155 LTOWB recipients eligible for matching. PSM and CEM reduced covariate imbalances between the CCT and LTOWB groups, with the exception that males remained over-represented in the LTOWB group due to the hospital's former resuscitation policy of not administering RhD-positive LTOWB to females <50. In both of the matched analyses, the LTOWB group received a median of 4 LTOWB units. There were no significant differences in 6-, 24-h mortality or 30-day mortality between groups, nor were there differences in the frequency of other clinical outcomes such as acute kidney injury, sepsis, venous/arterial thromboembolism; delta MODS was lower for the LTOWB recipients in the exact match group. CONCLUSION: In both matched analyses, administration of a median of four LTOWB units did not result in a different frequency of major clinical outcomes including mortality.