Individual clotting factor contributions to mortality following trauma

Abstract

BACKGROUND Acute traumatic coagulopathy (ATC) afflicts 20–30% of trauma patients, but the extensive collinearity of the coagulation cascade complicates attempts to clarify global clotting factor dysfunction. This study aims to characterize phenotypes of clotting factor dysfunction and their contributions to mortality after major trauma. METHODS This prospective cohort study examines all adult trauma patients of the highest activation level presenting to San Francisco General Hospital between 2/2005 and 2/2015. Factors II, V, VII, VIII, IX, X, and protein C activity on admission and mortality status at 28 days were assessed. Predictors of 28-day mortality in univariate analysis were included in multiple logistic regression controlling for traumatic brain injury (TBI), acidosis, age, and mechanism of injury. Principal component analysis (PCA) was utilized to identify phenotypic coagulation. RESULTS Complete coagulation factor data was available for 876/1,429 (61%). In multiple logistic regression, factors V (OR: 0.86, CI95%: 0.76–0.97), VIII (OR: 0.97, CI95%: 0.95–0.99), X (OR: 0.79, CI95%: 0.68–0.92), and protein C (OR: 1.17, CI95%: 1.05–1.30) significantly predicted 28-day mortality after controlling for age, base deficit, mechanism of injury, and TBI. PCA identified 2 significant principal components (Phenotypes 1 and 2) that accounted for 66.3% of the total variance. Phenotype 1 (factors II, VII, IX, X, and protein C abnormalities) explained 49.3% and was associated with increased injury, coagulopathy, TBI, and mortality. Phenotype 2 (factors V and VIII abnormalities) explained 17.0% and was associated with increased coagulopathy, blunt injury, and mortality. Only Phenotype 2 remained significantly associated with 28-day mortality in multiple logistic regression. CONCLUSIONS PCA identified 2 distinct phenotypes within the entirety of global clotting factor abnormalities, and these findings substantiate the crucial association of factors V and VIII on mortality following trauma. This may be the first step toward identifying unique phenotypes after injury and personalizing hemostatic resuscitation. LEVEL OF EVIDENCE Prognostic study, Level III

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