Background: Traumatic injury is a leading cause of death, in large part driven by coagulopathy associated hemorrhage and thrombotic complications. Identification of biological pathways and therapeutic targets has been limited. We performed a proteomic analysis using plasma isolated from trauma patients and assessed proteome relation to clot formation and stability. Methods: Platelet-poor plasma was isolated from trauma patients upon emergency department arrival. Coagulation was characterized using rheology, turbidity, and confocal microscopy. Proteomics were measured using liquid chromatography-mass spectrometry and compared between: (1) healthy donors vs. trauma patients, (2) non-severe vs. severe injury, (3) survived vs. deceased patients, (4) penetrating vs. blunt injuries, (5) traumatic brain injury (TBI) vs. No-TBI and (6) presence vs absence of physiological shock. Spearman correlations were calculated between coagulation tests, clinical vitals, and proteomics data. Gene Ontology and STRING analysis identified enrichment of biological processes and interconnectedness of mortality-related proteins. Results: Hemostatic processes were enriched in healthy donors, severe injury patients, surviving patients, No-TBI patients and patients not exhibiting shock. PAI-3 was in higher abundance in those who survived their injuries compared to those who died. PAI-3 was correlated with faster clotting time, thrombin generation, and decreased D-dimer. Proteins higher in deceased patients compared to those who survived, such as PTGDS, related to immune activity, correlated with weaker clots and increased D-dimer. Conclusions: This exploratory analysis of plasma proteomics in trauma patients identified potential markers related to coagulation and immune activity, which may contribute to coagulopathy associated mortality after injury and serve as therapeutic targets.
Gosselin et al. (Fri,) studied this question.