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.