Traumatic Inflammatory-Coagulation Coactivation Occurs Early After Injury and Impacts Mortality.

OBJECTIVES

Acute traumatic coagulopathy is known to occur early following severe injury. However, the role and impact of both pro- and anti-inflammatory cytokines are unknown. We aimed to investigate the inflammatory (pro- and anti-inflammatory cytokines) and coagulation pathways following injury and their relation to 30-day mortality.

DESIGN

Patients included in this analysis had complete data available for a panel of 48 coagulation and inflammatory biomarkers obtained from initial emergency department blood draws. Principal component analysis (PCA), a dimensionality-reduction machine learning method, was used to identify biomarker phenotypes present. Principal components with variance (eigenvalues) greater than 1 were selected for inclusion in the analysis. Least Absolute Shrinkage and Selection Operator regression was performed to identify independent predictors of 30-day mortality. The critical administration threshold (CAT, > 3 units of RBCs in 1 hr) was used to quantify bleeding.

SETTING

This is a secondary analysis of the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) study.

PATIENTS: The PROPPR study was a pragmatic, phase 3, multisite, randomized clinical trial that included 680 severely injured patients at 12 level 1 trauma centers.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN

RESULTS

Inflammatory and coagulation marker phenotypes were associated with 30-day mortality. Among 286 patients included, 30-day mortality was 24.4% ( n = 70). PCA found 14 phenotypes that collectively explained 83% of pathophysiologic variability. The top six principal components contributing to the early pathophysiology changes were a coagulopathy phenotype, followed by two distinct mixed inflammatory phenotypes, a platelet phenotype representing platelet activation integrins, von Willebrand Factor (vWF), and a thromboelastography phenotype representing clot strength and thrombin generation. Controlling for age, sex, injury mechanism, and bleeding (CAT+), mortality was predominantly driven by the coagulopathy phenotype 1 ( p = 0.0002) and mixed inflammatory phenotype 3 ( p = 0.0684).

CONCLUSIONS

These findings demonstrate that coagulation and inflammation are coactivated early after severe injury and are associated with poor outcomes. The activation of these pathways is both complex and integrated, involving inflammatory cytokines, chemokines, growth factors, coagulation factors, platelet activated integrins, vWF, and thrombin. This study uses the largest comprehensive array of coagulation and inflammatory biomarkers to date and identifies key biologic phenotypes linked to mortality after severe trauma.