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.

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.

Impact of hypocalcemia on mortality in pediatric trauma patients who require transfusion.

BACKGROUND: Admission hypocalcemia has been associated with poor outcomes in injured adults. The impact of hypocalcemia on mortality has not been widely studied in pediatric trauma. METHODS: A pediatric trauma center database was queried retrospectively (2013-2022) for children younger than 18 years who received blood transfusion within 24 hours of injury and had ionized calcium (iCal) level on admission. Children who received massive transfusion (>40 mL/kg) prior to hospital arrival or calcium prior to laboratory testing were excluded. Hypocalcemia was defined by the laboratory lower limit (iCal <1.00). Main outcomes were in-hospital mortality and 24-hour blood product requirements. Logistic regression analysis was performed to adjust for Injury Severity Score (ISS), admission shock index, Glasgow Coma Scale (GCS) score, and weight-adjusted total transfusion volume. RESULTS: In total, 331 children with median (IQR) age of 7 years (2-3 years) and median (IQR) ISS 25 (14-33) were included, 32 (10%) of whom were hypocalcemic on arrival to the hospital. The hypocalcemic cohort had higher ISS (median (IQR) 30(24-36) vs. 22 (13-30)) and lower admission GCS score (median (IQR) 3 (3-12) vs. 8 (3-15)). Age, sex, race, and mechanism were not significantly different between groups. On univariate analysis, hypocalcemia was associated with increased in-hospital (56% vs. 18%; p < 0.001) and 24-hour (28% vs. 5%; p < 0.001) mortality. Children who were hypocalcemic received a median (IQR) of 22 mL/kg (7-38) more in total weight-adjusted 24-hour blood product transfusion following admission compared to the normocalcemic cohort ( p = 0.005). After adjusting for ISS, shock index, GCS score, and total transfusion volume, hypocalcemia remained independently associated with increased 24-hour (odds ratio, 4.93; 95% confidence interval, 1.77-13.77; p = 0.002) and in-hospital mortality (odds ratio, 3.41; 95% confidence interval, 1.22-9.51; p = 0.019). CONCLUSION: Hypocalcemia is independently associated with mortality and receipt of greater weight-adjusted volumes of blood product transfusion after injury in children. The benefit of timely calcium administration in pediatric trauma needs further exploration. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Receipt of RhD-positive whole blood for life-threatening bleeding in female children: A survey in alloimmunized mothers regarding minimum acceptable survival benefit relative to risk of maternal alloimmunization to anti-D.

BACKGROUND: Low-titer group O whole blood (LTOWB) for treatment of hemorrhagic shock sometimes necessitates transfusion of RhD-positive units due to short supply of RhD-negative LTOWB. Practitioners must choose between using RhD-positive LTOWB when RhD-negative is unavailable against the risk to a female of childbearing potential of becoming RhD-alloimmunized, risking hemolytic disease of the fetus and newborn (HDFN) in future children, or using component therapy with RhD-negative red cells. This survey asked females with a history of red blood cell (RBC) alloimmunization about their risk tolerance of RhD alloimmunization compared to the potential for improved survival following transfusion of RhD-positive blood for an injured RhD negative female child. STUDY DESIGN AND METHODS: A survey was administered to RBC alloimmunized mothers. Respondents were eligible if they were living in the United States with at least one red cell antibody known to cause HDFN and if they had at least one RBC alloimmunized pregnancy. RESULTS: Responses from 107 RBC alloimmmunized females were analyzed. There were 32/107 (30%) with a history of severe HDFN; 12/107 (11%) had a history of fetal or neonatal loss due to HDFN. The median (interquartile range) absolute improvement in survival at which the respondents would accept RhD-positive transfusions for a female child was 4% (1%-14%). This was not different between females with and without a history of severe or fatal HDFN (p = .08 and 0.38, respectively). CONCLUSION: Alloimmunized mothers would accept the risk of D-alloimmunization in a RhD-negative female child for improved survival in cases of life-threatening bleeding.

Whole blood: total blood product ratio impacts survival in injured children.

INTRODUCTION: Some studies in both children and adults have shown a mortality benefit for the use of low titer group O whole blood (LTOWB) compared to component therapy for traumatic resuscitation. Although LTOWB is not widely available at pediatric trauma centers, its use is increasing. We hypothesized that in children who received whole blood after injury, the proportion of whole blood in relation to the total blood product resuscitation volume would impact survival. METHODS: The trauma database from a single academic pediatric level 1 trauma center was queried for pediatric (age < 18 years) recipients of LTOWB after injury (years 2015-2022). Weight-based blood product (LTOWB, red blood cells, plasma and platelet) transfusion volumes during the first 24 hours of admission were recorded. The ratio of LTOWB to total transfusion volume was calculated. The primary outcome was in-hospital mortality. Multivariable logistic regression model adjusted for the following variables: age, sex, mechanism of injury, injury severity score, shock index, and Glasgow Coma Scale (GCS) score. Adjusted odds ratio representing the change in the odds of mortality by a 10% increase in the LTOWB:total transfusion volume ratio was reported. RESULTS: There were 95 pediatric LTOWB recipients included in the analysis, with median (IQR) age of 10 years (5-14), 58% male, median (IQR) injury severity score of 26 (17-35), 25% penetrating mechanism. The median(IQR) volume of LTOWB transfused was 17 (15-35) mL/kg. LTOWB comprised a median (IQR) of 59% (33-100) of the total blood product resuscitation. Among patients who received LTOWB, there was a 38% decrease in in-hospital mortality for each 10% increase in the proportion of WB within total transfusion volume (p < 0.001) after adjusting for age, sex, mechanism of injury, injury severity score, shock index, and GCS score. CONCLUSION: Increased proportions of LTOWB within the total blood product resuscitation was independently associated with survival in injured children. Based on existing data that suggests safety and improved outcomes with whole blood, consideration may be given to increasing the use of LTOWB over CT resuscitation in pediatric trauma resuscitation. ARTICLE TYPE: Level 3 Evidence; Observational Cohort Study.

Massive Transfusion in Pediatric Patients on Extracorporeal Membrane Oxygenation: A Secondary Analysis of the Massive Transfusion in Children (MATIC) Study.

Few data describe pediatric patients who receive massive transfusion for life-threatening hemorrhage (LTH) while on extracorporeal membrane oxygenation (ECMO). We present a retrospective secondary analysis of a multicenter prospective observational study to describe resource utilization and mortality in pediatric patients with LTH while on ECMO. Children who were on ECMO during an LTH were compared to children with LTH who were not on ECMO. Primary outcomes were volumes of blood products administered and 28 day mortality. Comparisons were assessed by two-sided Fisher's exact test or Wilcoxon rank sum test. A total of 449 children, including 36 on ECMO, were included. Compared to those not on ECMO, children on ECMO received a higher volume of blood products (110 [50-223] vs. 59 [28-113]) ml/kg, p = 0.002) and were more likely to receive antifibrinolytic therapy (39% vs. 10%, p < 0.001). Blood product ratios were similar. Extracorporeal membrane oxygenation patients had higher 28 day mortality (64% vs. 35%, p = 0.001), although 24 hour mortality was similar (17% vs. 23%, p = 0.5). In conclusion, children on ECMO with LTH experience high resource utilization and 28 day mortality. Studies are needed to identify children at risk for LTH and to evaluate ECMO-specific treatment strategies.

The Efficacy of Low-Titer Group O Whole Blood Compared With Component Therapy in Civilian Trauma Patients: A Meta-Analysis.

OBJECTIVES: To assess if transfusion with low-titer group O whole blood (LTOWB) is associated with improved early and/or late survival compared with component blood product therapy (CT) in bleeding trauma patients. DATA SOURCES: A systematic search of PubMed, CINAHL, and Web of Science was performed from their inception through December 1, 2023. Key terms included injury, hemorrhage, bleeding, blood transfusion, and whole blood. STUDY SELECTION: All studies comparing outcomes in injured civilian adults and children who received LTOWB versus CT were included. DATA EXTRACTION: Data including author, publication year, sample size, total blood volumes, and clinical outcomes were extracted from each article and reported following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Main outcomes were 24-hour (early) and combined 28-day, 30-day, and in-hospital (late) mortality rates between recipients of LTOWB versus CT, which were pooled using random-effects models. DATA SYNTHESIS: Of 1297 studies reviewed, 24 were appropriate for analysis. Total subjects numbered 58,717 of whom 5,164 received LTOWB. Eleven studies included adults-only, seven included both adults and adolescents, and six only included children. The median (interquartile range) age for patients who received LTOWB and CT was 35 years (24-39) and 35.5 years (23-39), respectively. Overall, 14 studies reported early mortality and 22 studies reported late mortality. LTOWB was associated with improved 24-hour survival (risk ratios [RRs] [95% CI] = 1.07 [1.03-1.12]) and late (RR [95% CI] = 1.05 [1.01-1.09]) survival compared with component therapy. There was no evidence of small study bias and all studies were graded as a moderate level of bias. CONCLUSIONS: These data suggest hemostatic resuscitation with LTOWB compared with CT improves early and late survival outcomes in bleeding civilian trauma patients. The majority of subjects were injured adults; multicenter randomized controlled studies in injured adults and children are underway to confirm these findings.

Increased platelet to red blood cell transfusion ratio associated with acute kidney injury in children with life-threatening bleeding.

INTRODUCTION: Transfusion may increase the risk of organ failure through immunomodulatory effects. The primary objective of this study was to assess for patient or transfusion-related factors that are independently associated with the risk of acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in a cohort of children with life-threatening bleeding from all etiologies. METHODS: In a secondary analysis of the prospective observational massive transfusion in children (MATIC) study, multivariable logistic regression was performed in an adjusted analysis to determine if blood product ratios or deficits were independently associated with AKI or ARDS in children with life-threatening bleeding. RESULTS: There were 449 children included with a median (interquartile range, IQR) age of 7.3 years (1.7-14.7). Within 5 days of the life-threatening bleeding event, AKI occurred in 18.5% and ARDS occurred in 20.3% of the subjects. Every 10% increase in the platelet to red blood cell transfusion ratio is independently associated with a 12.7% increase in the odds of AKI (adjusted odds ratio 1.127; 95% confidence interval 1.025-1.239; p-value .013). Subjects with operative or medical etiologies were independently associated with an increased risk of AKI compared to those with traumatic injury. No transfusion-related variables were independently associated with the risk of developing ARDS. CONCLUSION: The use of increased platelet to red blood cell transfusion ratios in children with life-threatening bleeding of any etiology may increase the risk of AKI but not ARDS. Prospective trials are needed to determine if increased platelet use in this cohort increases the risk of AKI to examine possible mechanisms.

Patient sex and outcomes in children with life-threatening hemorrhage.

BACKGROUND: Recent data suggest female sex imparts a survival benefit after trauma in adults. The independent associations between patient sex and age with outcomes have not been examined in children with life-threatening hemorrhage (LTH) from all etiologies. STUDY DESIGN AND METHODS: In a secondary analysis of a multicenter prospective observational study of children with LTH, Massive Transfusion in Children (MATIC), we analyzed if patient sex and age were associated with differences in severity of illness, therapies, and outcomes. Primary outcomes were 24 hour mortality and weight-adjusted transfusion volume during LTH. Kruskal-Wallis, chi-square testing, and multivariable linear regression were used for adjusted analyses. RESULTS: Of 449 children, 45% were females and 55% were males. Females were more commonly younger, white, and with less trauma as the etiology of LTH compared to males. Markers of clinical severity were similar between groups, except injury severity score (ISS) was higher in females in the trauma subgroup. In terms of resuscitative practices, females received greater weight-adjusted total transfusion volumes compared to males (76 (40-150) mL/kg vs. 53 (24-100) mL/kg), as well as increased red blood cells (RBCs), plasma, and platelets compared to males. After adjustment for confounders, female sex and age 0-11 years were independently associated with increased transfusion volume during LTH. There were no differences in mortality or adverse outcomes according to patient sex. CONCLUSION: Patient sex and age may impact factors associated with LTH and therapies received. Studies in developmental hemostasis are needed to determine the optimal transfusion strategy for LTH according to patient sex and age.

Survey of policies at US hospitals on the selection of RhD type of low-titer O whole blood for use in trauma resuscitation.

BACKGROUND: Low-titer group O whole blood (LTOWB) use is increasing due to data suggesting improved outcomes and safety. One barrier to use is low availability of RhD-negative LTOWB. This survey examined US hospital policies regarding the selection of RhD type of blood products in bleeding emergencies. STUDY DESIGN AND METHODS: A web-based survey of blood bank directors was conducted to determine their hospital's RhD-type selection policies for blood issued for massive bleeding. RESULTS: There was a 61% response rate (101/157) and of those responses, 95 were complete. Respondents indicated that 40% (38/95) use only red blood cells (RBCs) and 60% (57/95) use LTOWB. For hospitals that issue LTOWB (N = 57), 67% are supplied only with RhD-positive, 2% only with RhD-negative, and 32% with both RhD-positive and RhD-negative LTOWB. At sites using LTOWB, RhD-negative LTOWB is used exclusively or preferentially more commonly in adult females of childbearing potential (FCP) (46%) and pediatric FCP (55%) than in men (4%) and boys (24%). RhD-positive LTOWB is used exclusively or preferentially more commonly in men (94%) and boys (54%) than in adult FCP (40%) or pediatric FCP (21%). At sites using LTOWB, it is not permitted for adult FCPs at 12%, pediatric FCP at 21.4%, and boys at 17.1%. CONCLUSION: Hospitals prefer issuing RhD-negative LTOWB for females although they are often ineligible to receive RhD-negative LTOWB due to supply constraints. The risk and benefits of LTOWB compared to the rare occurrence of hemolytic disease of the fetus/newborn (HDFN) need further examination in the context of withholding a therapy for females that has the potential for improved outcomes.

Maternal and child life years gained by transfusing low titer group O whole blood in trauma: A computer simulation.

BACKGROUND: Using low titer group O whole blood (LTOWB) is increasingly popular for resuscitating trauma patients. LTOWB is often RhD-positive, which might cause D-alloimmunization and hemolytic disease of the fetus and newborn (HDFN) if transfused to RhD-negative females of childbearing potential (FCP). This simulation determined the number of life years gained by the FCP and her future children if she was resuscitated with LTOWB compared with conventional component therapy (CCT). METHODS: The model simulated 500,000 injured FCPs of each age between 0 and 49 years with LTOWB mortality relative reductions (MRRs) compared with components between 0.1% and 25%. For each surviving FCP, number of life years gained was calculated using her age at injury and average life expectancy for American women. The number of expected future pregnancies for FCPs that did not survive was also based on her age at injury; each future child was assigned the maximum lifespan unless they suffered perinatal mortality or serious neurological events from HDFN. RESULTS: The LTOWB group with an MRR 25% compared with CCT had the largest total life years gained. The point of equivalence for RhD-positive LTOWB compared to CCT, where life years lost due to severe HDFN was equivalent to life years gained due to FCP survival/future childbearing, occurred at an MRR of approximately 0.1%. CONCLUSION: In this model, RhD-positive LTOWB resulted in substantial gains in maternal and child life years compared with CCT. A >0.1% relative mortality reduction from LTOWB offset the life years lost to HDFN mortality and severe neurological events.

Another piece of the hemolytic disease of the fetus and newborn puzzle after RhD-positive transfusion in trauma resuscitation: the proportion of pregnant women who produce high titer anti-D.

Background: After the transfusion of RhD-positive red blood cell (RBC)-containing products to an RhD-negative woman of childbearing potential (WCP) during trauma resuscitation, there are several events that must occur for that WCP to have a future pregnancy affected by hemolytic disease of the fetus and newborn (HDFN). This study identified and quantitated the frequency of a novel event in the sequence from RhD-positive transfusion during trauma resuscitation to an HDFN outcome, that is, the development of a high titer anti-D among women who were D-alloimmunized. Methods: The transfusion service records at one maternity hospital were searched to locate all anti-D titers that had been performed on pregnant women between 1996 and 2022. The highest titer score during each pregnancy was recorded for this study. The critical titer threshold at this institution was ≥16. Passive anti-D caused by Rh immunoglobulin were excluded from analysis. Results: There were 97 pregnancies in 85 patients who had an immune-stimulated anti-D; in 60 of 97 (62%) pregnancies, the highest titer score was ≥16. There were 12 patients who had titers performed in two pregnancies during the study period; the correlation between the maximum titer in each pregnancy was not statistically significant (Spearman rank correlation r=0.42, p=0.17). Conclusion: In this single center study, 62% of D-alloimmunized pregnant women had a high titer antibody. When considering all of the events that must occur for HDFN to happen, the rate of perinatal mortality was calculated to be 0.04% and the rate of perinatal death or serious adverse event from HDFN was 0.24%.

Use of whole blood in pediatric trauma: a narrative review.

Balanced hemostatic resuscitation has been associated with improved outcomes in patients with both pediatric and adult trauma. Cold-stored, low-titer group O whole blood (LTOWB) has been increasingly used as a primary resuscitation product in trauma in recent years. Benefits of LTOWB include rapid, balanced resuscitation in one product, platelets stored at 4°C, fewer additives and fewer donor exposures. The major theoretical risk of LTOWB transfusion is hemolysis, however this has not been shown in the literature. LTOWB use in injured pediatric populations is increasing but is not yet widespread. Seven studies to date have described the use of LTOWB in pediatric trauma cohorts. Safety of LTOWB use in both group O and non-group O pediatric patients has been shown in several studies, as indicated by the absence of hemolysis and acute transfusion reactions, and comparable risk of organ failure. Reported benefits of LTOWB included faster resolution of shock and coagulopathy, lower volumes of transfused blood products, and an independent association with increased survival in massively transfused patients. Overall, pediatric data are limited by small sample sizes and mostly single center cohorts. Multicenter randomized controlled trials are needed.

Therapeutic plasma exchange is feasible and tolerable in severely injured patients with trauma-induced coagulopathy.

Objectives: Trauma-induced coagulopathy (TIC) occurs in a subset of severely injured trauma patients. Despite having achieved surgical hemostasis, these individuals can have persistent bleeding, clotting, or both in conjunction with deranged coagulation parameters and typically require transfusion support with plasma, platelets, and/or cryoprecipitate. Due to the multifactorial nature of TIC, targeted interventions usually do not have significant clinical benefits. Therapeutic plasma exchange (TPE) is a non-specific modality of removing and replacing a patient's plasma in a euvolemic manner that can temporarily normalize coagulation parameters and remove deleterious substances, and may be beneficial in such patients with TIC. Methods: In a prospective case series, TPE was performed in severely injured trauma patients diagnosed with TIC and transfusion requirement. These individuals all underwent a series of at least 3 TPE procedures performed once daily with plasma as the exclusive replacement fluid. Demographic, injury, laboratory, TPE, and outcome data were collected and analyzed. Results: In total, 7 patients received 23 TPE procedures. All patients had marked improvements in routine coagulation parameters, platelet counts, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activities, inflammatory markers including interleukin-6 concentrations, and organ system injuries after completion of their TPE treatments. All-cause mortality rates at 1 day, 7 days, and 30 days were 0%, 0%, and 43%, respectively, and all patients for whom TPE was initiated within 24 hours after injury survived to the 30-day timepoint. Surgical, critical care, and apheresis nursing personnel who were surveyed were universally positive about the utilization of TPE in this patient population. These procedures were tolerated well with the most common adverse event being laboratory-diagnosed hypocalcemia. Conclusion: TPE is feasible and tolerable in severely injured trauma patients with TIC. However, many questions remain regarding the application of TPE for these critically ill patients including identification of the optimal injured population, ideal time of treatment initiation, appropriate treatment intensity, and concurrent use of adjunctive treatments. Level of evidence: Level V.

Endotheliopathy of trauma in children: The association of syndecan-1 with injury and poor outcomes.

BACKGROUND: The contribution of the endothelium to trauma-induced coagulopathy has not been thoroughly investigated in injured children. METHODS: This is a prospective cohort study of children (younger than 18 years) who presented with a potentially severe injury to an academic pediatric trauma center. Syndecan-1 level was collected on arrival and 24 hours following hospital arrival. Children were categorized as injured versus uninjured based on results of trauma evaluation. Demographics, injury characteristics, vital signs, and clinical laboratories were recorded. A composite clinical outcome was defined as death or blood product transfusion within 24 hours of hospital arrival. Statistical tests determined the impact of injury characteristics and therapeutics on syndecan-1 levels and assessed for associations between syndecan-1 level and outcomes. RESULTS: A total of 121 subjects were included in the analysis: 96 injured (79%) and 25 uninjured (21%). There were no differences between groups in age (median [interquartile range (IQR)], 11 [4-14] years), sex, or race. The injured cohort had a median (IQR) Injury Severity Score of 16 (9-21), 75% had blunt mechanism, 26% were transfused within 6 hours, 3% had 24-hour mortality, and 6% had in-hospital mortality. Median (IQR) syndecan-1 level on admission was significantly higher in injured versus uninjured cohort (44 [21-75] vs. 25 [17-42]; p = 0.04). Admission base deficit was significantly correlated with syndecan-1 level ( r = 0.8, p < 0.001); no association with traumatic brain injury or injury mechanism was seen. Children with elevated syndecan-1 on admission had significantly increased odds of poor outcome; every 10 ng/mL increase in syndecan-1 was associated with 10% increased odds of death or transfusion ( p < 0.001). Transfusion with any blood product was associated with a significant decrease in syndecan-1 from arrival to 24 hours (Δ syndecan-1, -17 [-64 to -5] vs. -8 [-19 to +2]; p < 0001). CONCLUSION: Elevated admission syndecan-1 level, suggestive of endotheliopathy, was associated with shock and poor outcomes in pediatric trauma. Larger cohort studies are required to fully describe the complexities of trauma-induced coagulopathy and investigate the benefit of therapies targeting endotheliopathy in children. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Incompatible plasma transfusion is not associated with increased mortality in civilian trauma patients.

BACKGROUND: The introduction of low titer group O whole blood (LTOWB) that contains potentially ABO-incompatible plasma and the increasing use of group A plasma, due to shortages of AB plasma, in trauma patients whose ABO group is unknown could put the recipients of incompatible plasma at risk of increased morbidity and mortality. This study evaluated civilian trauma patient outcomes following receipt of incompatible plasma. METHODS: One trauma center's patient contributions to three multicenter studies of different trauma resuscitation strategies was analyzed; these patients were separated into two groups based on receipt of only compatible plasma versus receipt of any quantity of incompatible plasma. Multivariate analysis was performed to determine if receipt of incompatible plasma was associated with 24-hour or 30-day mortality. RESULTS: There were 347 patients eligible for this secondary analysis with 167 recipients of only compatible plasma and 180 recipients of incompatible plasma. The two groups were well matched demographically and on both prehospital and hospital arrival vital signs. The median (IQR) volume of incompatible plasma received by these patients was 684 ml (342, 1229). There was not a significant difference between the groups in 24-hour and 30-day mortality, nor in in-hospital or intensive care unit lengths of stay. In the Cox proportional-hazards regression model for both 24-hour and 30-day survival, receipt of incompatible plasma was not independently predictive of either mortality endpoint. CONCLUSION: Receipt of incompatible plasma was not independently associated with increased mortality in trauma patients. Prospective studies are needed to confirm these findings.

Age-related changes in thromboelastography profiles in injured children.

BACKGROUND: The role of age in mediating coagulation characteristics in injured children is not well defined. We hypothesize thromboelastography (TEG) profiles are unique across pediatric age groups. METHODS: Consecutive trauma patients younger than 18 years from a Level I pediatric trauma center database from 2016 to 2020 with TEG obtained on arrival to the trauma bay were identified. Children were categorized by age according to the National Institute of Child Health and Human Development categories (infant, ≤1 year; toddler, 1-2 years; early childhood, 3-5 years; older childhood, 6-11 years; adolescent, 12-17 years). Thromboelastography values were compared across age groups using Kruskal-Wallis and Dunn's tests. Analysis of covariance was performed controlling for sex, Injury Severity Score (ISS), arrival Glasgow Coma Scale (GCS) score, shock, and mechanism of injury. RESULTS: In total, 726 subjects were identified; 69% male, median (interquartile range [IQR]) ISS = 12 (5-25), and 83% had a blunt mechanism. On univariate analysis, there were significant differences in TEG α-angle ( p < 0.001), MA ( p = 0.004), and fibrinolysis 30 minutes after MA (LY30) ( p = 0.01) between groups. In post hoc tests, the infant group had significantly greater α-angle (median, 77; IQR, 71-79) and MA (median, 64; IQR, 59-70) compared with other groups, while the adolescent group had significantly lower α-angle (median, 71; IQR, 67-74), MA (median, 60; IQR, 56-64), and LY30 (median, 0.8; IQR, 0.2-1.9) compared with other groups. There were no significant differences between toddler, early childhood, and middle childhood groups. On multivariate analysis, the relationship between age group and TEG values (α-angle, MA, and LY30) persisted after controlling for sex, ISS, GCS, shock, and mechanism of injury. CONCLUSION: Age-associated differences in TEG profiles across pediatric age groups exist. Further pediatric-specific research is required to assess whether the unique profiles at extremes of childhood translate to differential clinical outcomes or responses to therapies in injured children. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Damage-control resuscitation in pediatric trauma: What you need to know.

ABSTRACT: Damage-control resuscitation (DCR) consists of rapid control of bleeding, avoidance of hemodilution, acidosis, and hypothermia; early empiric balanced transfusions with red blood cells, plasma and platelets, or whole blood when available, and the use of intravenous or mechanical hemostatic adjuncts when indicated. The principles used in pediatric and adult trauma patients are quite similar. There are very important recognized physiologic differences in children with traumatic hemorrhagic shock that warrant slight variations in DCR. In pediatric trauma patients, early physiologic signs of shock may be different from adults and the early recognition of this is critical to enable prompt resuscitation and utilization of damage control principles. This review details the current principles of pediatric DCR based on the best available literature, expert consensus recommendations, and also describes a practical guide for implementation of DCR strategies for pediatric trauma patients.

Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial.

BACKGROUND: In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial. METHODS: We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors. RESULTS: We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days ( p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors ( p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors ( p = 0.03). CONCLUSION: Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.