Patterns of trauma-induced coagulopathy in injured children: A principal component analysis investigating endothelial, coagulation, and platelet biomarkers

Background: Trauma-induced coagulopathy is common and associated with poor outcomes in injured children. Our aim was to identify patterns of coagulopathy after injury using endothelial, platelet, and coagulation biomarkers, and associate these phenotypes with relevant patient factors and clinical outcomes in a pediatric trauma cohort.

Methods: Principal component (PC) analysis was performed on data from injured children between 2018 and 2022. Laboratories included endothelial markers (syndecan-1, thrombomodulin, tissue factor, and vascular endothelial growth factor), international normalized ratio, platelet count, rapid thromboelastography maximum amplitude, and base deficit. Variables were reduced to PCs; PC scores were generated for each subject and used in logistic regression with outcomes including mortality, blood transfusion, shock (pediatric-adjusted shock index), and patient characteristics including age, sex, injury mechanism, and traumatic brain injury.

Results: In total, 59 children had complete data for analysis. Median (interquartile range) age was 10 (4-14) years, 31% female, 21% penetrating mechanism, and median (interquartile range) injury severity score of 16 (9-21). Principal component analysis identified two significant PCs accounting for 67% of overall variance. PC1 included syndecan-1, thrombomodulin, vascular endothelial growth factor, international normalized ratio, and base deficit; PC1 scores were associated with mortality, blood transfusion, and shock (all p < 0.001). PC2 included tissue factor, platelet count, and rapid thromboelastography maximum amplitude; PC2 scores were associated with age (ρ = -0.42, p = 0.001) but no studied clinical outcome. Neither PC was significantly associated with sex, injury mechanism, or traumatic brain injury.

Conclusion: Principal component analysis detected two distinct biomarker patterns in injured children involving the domains of the endothelium, coagulation, and platelets. The first phenotype was associated with poor clinical outcomes, while the second was associated with age. This supports the concept that pediatric trauma-induced coagulopathy elicits a heterogeneous response, and suggests that there may be a prognostic value to these phenotypes that warrants further investigation.

Level of evidence: Prognostic and Epidemiological; Level IV.