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.

Transfusion Ratios and Deficits in Injured Children With Life-Threatening Bleeding.

OBJECTIVES: To assess the impact of plasma and platelet ratios and deficits in injured children with life-threatening bleeding. DESIGN: Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a prospective observational study of children with life-threatening bleeding events. SETTING: Twenty-four childrens hospitals in the United States, Canada, and Italy. PATIENTS: Injured children 0-17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under activation of massive transfusion protocol. INTERVENTION/EXPOSURE: Weight-adjusted blood product volumes received during the bleeding event were recorded. Plasma:RBC ratio (plasma/RBC weight-adjusted volume in mL/kg) and platelet:RBC ratio (platelet/RBC weight-adjusted volume in mL/kg) were analyzed. Plasma deficit was calculated as RBC mL/kg - plasma mL/kg; platelet deficit was calculated as RBC mL/kg - platelet mL/kg. MEASUREMENTS AND MAIN RESULTS: Of 191 patients analyzed, median (interquartile range) age was 10 years (5-15 yr), 61% were male, 61% blunt mechanism, and median (interquartile range) Injury Severity Score was 29 (24-38). After adjusting for Pediatric Risk of Mortality score, cardiac arrest, use of vasoactive medications, and blunt mechanism, a high plasma:RBC ratio (> 1:2) was associated with improved 6-hour survival compared with a low plasma:RBC ratio (odds ratio [95% CI] = 0.12 [0.03-0.52]; p = 0.004). Platelet:RBC ratio was not associated with survival. After adjusting for age, Pediatric Risk of Mortality score, cardiac arrest, and mechanism of injury, 6-hour and 24-hour mortality were increased in children with greater plasma deficits (10% and 20% increased odds of mortality for every 10 mL/kg plasma deficit at 6 hr [p = 0.04] and 24 hr [p = 0.01], respectively); 24-hour mortality was increased in children with greater platelet deficits (10% increased odds of 24-hr mortality for every 10 mL/kg platelet deficit [p = 0.02)]). CONCLUSIONS: In injured children, balanced resuscitation may improve early survival according to this hypothesis generating study. Multicenter clinical trials are needed to assess whether clinicians should target ratios and deficits as optimal pediatric hemostatic resuscitation practice.

Use of Antifibrinolytics in Pediatric Life-Threatening Hemorrhage: A Prospective Observational Multicenter Study.

OBJECTIVES: To assess the impact of antifibrinolytics in children with life-threatening hemorrhage. DESIGN: Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a prospective observational study of children with life-threatening bleeding events. SETTING: Twenty-four children's hospitals in the United States, Canada, and Italy. PATIENTS: Children 0-17 years old who received greater than 40 mL/kg of total blood products over 6 hours or were transfused under activation of massive transfusion protocol. INTERVENTION/EXPOSURE: Children were compared according to receipt of antifibrinolytic medication (tranexamic acid or aminocaproic acid) during the bleeding event. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, medications administered, and clinical outcomes were analyzed using Cox proportional hazard and Kaplan-Meier survival analysis. The primary outcome was 24-hour mortality. Of 449 patients analyzed, median age was 7 years (2-15 yr), and 55% were male. The etiology of bleeding was 46% traumatic, 34% operative, and 20% medical. Twelve percent received antifibrinolytic medication during the bleeding event (n = 54 unique subjects; n = 18 epsilon aminocaproic acid, n = 35 tranexamic acid, and n = 1 both). The antifibrinolytic group was comparable with the nonantifibrinolytic group on baseline demographic and physiologic parameters; the antifibrinolytic group had longer massive transfusion protocol duration, received greater volume blood products, and received factor VII more frequently. In the antifibrinolytic group, there was significantly less 6-hour mortality overall (6% vs 17%; p = 0.04) and less 6-hour mortality due to hemorrhage (4% vs 14%; p = 0.04). After adjusting for age, bleeding etiology, Pediatric Risk of Mortality score, and plasma deficit, the antifibrinolytic group had decreased mortality at 6- and 24-hour postbleed (adjusted odds ratio, 0.29 [95% CI, 0.09-0.93]; p = 0.04 and adjusted odds ratio, 0.45 [95% CI, 0.21-0.98]; p = 0.04, respectively). CONCLUSIONS: Administration of antifibrinolytic medications during the life-threatening event was independently associated with improved 6- and 24-hour survivals in bleeding children. Consideration should be given to use of antifibrinolytics in pediatric patients with life-threatening hemorrhage.

Whole Blood is Superior to Component Transfusion for Injured Children: A Propensity Matched Analysis.

OBJECTIVE: To compare a propensity-matched cohort of injured children receiving conventional blood component transfusion to injured children receiving low-titer group O negative whole blood. SUMMARY OF BACKGROUND DATA: Transfusion of whole blood in pediatric trauma patients is feasible and safe. Effectiveness has not been evaluated. METHODS: Injured children ≥1 years old can receive up to 40 mL/kg of cold-stored, uncrossmatched whole blood during initial hemostatic resuscitation. Whole blood recipients (2016-2019) were compared to a propensity-matched cohort who received at least 1 uncrossmatched red blood cell unit in the trauma bay (2013-2016). Cohorts were matched for age, hypotension, traumatic brain injury, injury mechanism, and need for emergent surgery. Outcomes included time to resolution of base deficit, product volumes transfused, and INR after resuscitation. RESULTS: Twenty-eight children who received whole blood were matched to 28 children who received components. The whole blood group had faster time to resolution of base deficit [median (IQR) 2 (1-2.5) hours vs 6 (2-24) hours, respectively; P < 0.001]. The post-transfusion INR was decreased in whole blood vs component cohort [median (IQR) 1.4 (1.3-1.5) vs 1.6 (1.4-2.2); P = 0.01]. Lower plasma volumes [median (IQR) = 5 (0-15) mL/kg vs 11 (5-35) mL/kg; P = 0.04] and lower platelet volumes [median (IQR) = 0 (0-2) vs 3 (0-8); P = 0.03] were administered to the whole blood group versus component group. Other clinical variables (in-hospital death, hospital length of stay, intensive care unit length of stay, and ventilator days) did not differ between groups. CONCLUSIONS: Compared to component transfusion, whole blood transfusion results in faster resolution of shock, lower post-transfusion INR, and decreased component product transfusion. Larger cohorts are required to support these findings.

Window of Opportunity to Mitigate Trauma-induced Coagulopathy: Fibrinolysis Shutdown not Prevalent Until 1 Hour Post-injury.

OBJECTIVE: The aim of this study was to delineate the kinetics of coagulation dysregulation after injury in children. SUMMARY BACKGROUND DATA: Trauma-induced coagulopathy is common and portends poor outcomes in severely-injured children. Transfer to pediatric trauma centers is common; time from injury to laboratory testing is therefore highly variable. METHODS: Records of severely injured children age <18 years with rapid thromboelastography (TEG) on arrival and documented time of injury were queried. Standard definitions of hyperfibrinolysis (LY30 ≥3), fibrinolysis shutdown (SD; LY30 ≤0.8), and physiologic (LY30 = 0.9-2.9) were applied. Abbreviated Injury Scale score ≥3 defined severe traumatic brain injury (TBI). Variables of interest included demographics, injury mechanism, medications, mortality, and functional disability. Wilcoxon rank-sum and Kruskal-Wallis testing were utilized for skewed continuous data, and Chi-square or Fisher exact test was used for categorical data. To determine independent predictors of SD, multivariable logistic regression modeling was performed using the time from injury variable as well as variables determined a priori to be clinically relevant contributors to the development of SD (TBI, injury mechanism, and age). RESULTS: A total of 285 patients were included: median (interquartile range) age = 11 (6-15), injury severity score = 17 (10-25), 75% blunt mechanism, 32% severe TBI, 11% mortality, 28% functional disability. None received antifibrinolytics or blood products before TEG testing. Physiologic phenotype was predominant within 1 hour of injury (51%); beyond 1 hour, fibrinolysis SD was the predominant phenotype (1-3 hours = 46%, >3 hours = 59%). Patients with TBI had significant increase in incidence of fibrinolysis SD beyond 1 hour after injury as compared to non-TBI patients. Physiologic fibrinolysis was associated with survival at all timepoints (P = 0.005). CONCLUSIONS: Fibrinolysis SD is a reactive, compensatory mechanism that is evident soon after injury. There appears to be an early and brief window of opportunity for intervention to mitigate the progression to TIC. Further studies should focus on understanding the dynamic events occurring immediately after injury to identify specific targets for intervention.

Principal component analysis of coagulation assays in severely injured children.

BACKGROUND: Trauma-induced coagulopathy is common and associated with poor outcome in injured children. Our aim is to identify patterns of coagulation dysregulation after injury and associate these phenotypes with relevant clinical outcomes. METHODS: We performed principal components analysis on prospectively collected data from children with the highest-level trauma activation June 2015-June 2016. Parameters included admission international normalized ratio, platelet count and thromboelastograms. Variables were reduced to principal components; principal component scores were generated for each subject and used in logistic regression with outcomes including mortality, disability, venous thromboembolism, and blood transfusion in the first 24 hours. RESULTS: We included 133 subjects with median interquartile range age =10 (5-13 years), median interquartile range Injury Severity Score =17 (9-25), 73.5% boys, 70.8% blunt trauma. principal component analysis identified 3 significant principal components accounting for 75.0% of overall variance. Principal component 1 reflected clot strength; principal component 2 reflected abnormal fibrinolysis, both hyperfibrinolysis and fibrinolysis shutdown; principal component 3 reflected global clotting factor depletion. High principal component 1 score was associated with increased mortality (odds ratio =1.63) and blood transfusion (odds ratio 1.36). Principal component 2 score was correlated with Injury Severity Score (rho 0.4) and associated with venous thromboembolism (odds ratio 1.84), functional disability (odds ratio 1.66), mortality (odds ratio 2.07) and blood transfusion (odds ratio 2.79). PC3 score was associated with increased mortality (odds ratio 1.92) and blood transfusion (odds ratio 1.25). CONCLUSION: Principal component analysis detects 3 patterns of coagulation dysregulation using widely available laboratory parameters: (1) abnormalities in clot strength; (2) abnormalities in fibrinolysis, and (3) clotting factor depletion. While all were associated with mortality and transfusion, fibrinolytic dysregulation was associated with injury severity and portends particularly poor outcome including venous thromboembolism and disability.

Trending Fibrinolytic Dysregulation: Fibrinolysis Shutdown in the Days After Injury Is Associated With Poor Outcome in Severely Injured Children.

OBJECTIVE: To trend fibrinolysis after injury and determine the influence of traumatic brain injury (TBI) and massive transfusion on fibrinolysis status. BACKGROUND: Admission fibrinolytic derangement is common in injured children and adults, and is associated with poor outcome. No studies examine fibrinolysis days after injury. METHODS: Prospective study of severely injured children at a level 1 pediatric trauma center. Rapid thromboelastography was obtained on admission and daily for up to 7 days. Standard definitions of hyperfibrinolysis (HF; LY30 ≥3), fibrinolysis shutdown (SD; LY30 ≤0.8), and normal (LY30 = 0.9-2.9) were applied. Antifibrinolytic use was documented. Outcomes were death, disability, and thromboembolic complications. Wilcoxon rank-sum and Fisher exact tests were performed. Exploratory subgroups included massively transfused and severe TBI patients. RESULTS: In all, 83 patients were analyzed with median (interquartile ranges) age 8 (4-12) and Injury Severity Score 22 (13-34), 73.5% blunt mechanism, 47% severe TBI, 20.5% massively transfused. Outcomes were 14.5% mortality, 43.7% disability, and 9.8% deep vein thrombosis. Remaining in or trending to SD was associated with death (P = 0.007), disability (P = 0.012), and deep vein thrombosis (P = 0.048). Median LY30 was lower on post-trauma day (PTD)1 to PTD4 in patients with poor compared with good outcome; median LY30 was lower on PTD1 to PTD3 in TBI patients compared with non-TBI patients. HF without associated shutdown was not related to poor outcome, but extreme HF (LY30 >30%, n = 3) was lethal. Also, 50% of massively transfused patients in hemorrhagic shock demonstrated SD physiology on admission. All with HF (fc31.2%) corrected after hemostatic resuscitation without tranexamic acid. CONCLUSIONS: Fibrinolysis shutdown is common postinjury and predicts poor outcomes. Severe TBI is associated with sustained shutdown. Empiric antifibrinolytics for children should be questioned; thromboelastography-directed selective use should be considered for documented HF.

Computed tomography abbreviated assessment of sarcopenia following trauma: The CAAST measurement predicts 6-month mortality in older adult trauma patients.

BACKGROUND: Older adult trauma patients are at increased risk of poor outcome, both immediately after injury and beyond hospital discharge. Identifying patients early in the hospital stay who are at increased risk of death after discharge can be challenging. METHODS: Retrospective analysis was performed using our trauma registry linked with the social security death index from 2010 to 2014. Age was categorized as 18 to 64 and 65 years or older. We calculated mortality rates by age category then selected elderly patients with mechanism of injury being a fall for further analysis. Computed Tomography Abbreviated Assessment of Sarcopenia for Trauma (CAAST) was obtained by measuring psoas muscle cross-sectional area adjusted for height and weight. Kaplan-Meier survival analysis was performed, and proportional hazards regression modeling was used to determine independent risk factors for in-hospital and out-of-hospital mortality. RESULTS: A total of 23,622 patients were analyzed (16,748, aged 18-64 years; and 6,874, aged 65 or older). In-hospital mortality was 1.96% for ages 18 to 64 and 7.19% for age 65 or older (p < 0.001); postdischarge 6-month mortality was 1.1% for ages 18 to 64 and 12.86% for age 65 or older (p < 0.001). Predictors of in-hospital and postdischarge mortality for ages 18 to 64 and in-hospital mortality for ages 65 or older group included injury characteristics such as ISS, admission vitals, and head injury. Predictors of postdischarge mortality for age 65or older included skilled nursing before admission, disposition, and mechanism of injury being a fall. A total of 57.5% (n = 256) of older patients who sustained a fall met criteria for sarcopenia. Sarcopenia was the strongest predictor of out-of-hospital mortality in this cohort with a hazard ratio of 4.77 (95% confidence interval, 2.71-8.40; p < 0.001). CONCLUSION: Out of hospital does not assure out of danger for the elderly. Sarcopenia is a strong predictor of 6-month postdischarge mortality for older adults. The CAAST measurement is an efficient and inexpensive measure that can allow clinicians to target older trauma patients at risk of poor outcome for early intervention and/or palliative care services. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.