Defining and assessing the endotheliopathy of trauma and its implications on trauma-induced coagulopathy and trauma-related outcomes

The endothelium is a heterogeneous and dynamic organ that communicates systemically in both health and disease. Trauma-induced coagulopathy (TIC) is a significant contributor to morbidity and mortality in severe trauma and the hemostatic dysfunction that occurs as part of TIC is closely connected to the endothelium. The endotheliopathy of trauma (EOT) is a relatively new term that encompasses the combination of endothelial dysfunction, aberrant coagulopathy, and inflammation, all of which ensue after severe trauma and hemorrhage. The relationships that encompass EOT have yet to be fully elucidated; however. several key insights have been learned in recent years. In severe trauma and resultant hemorrhagic shock, there is degradation of the endothelial glycocalyx, leading to endothelial activation which controls the dysregulation of the clotting cascade seen locally and systemically in TIC. Further, there is disruption of endothelial tight and adherens junctions, which worsens shock physiology and further propagates coagulopathy. Serum biomarkers and visualization of the endothelium may provide clinical clues about phenotypes associated with poor outcomes; however, the heterogeneity of the endothelium and the dynamic changes that take place throughout the post-injury course add a complexity that has yet to be understood. Transfusion with balanced ratios of plasma, platelets, and red blood cells has been shown to improve outcomes following trauma and part of this improvement may be due to the inhibition of endothelial cell permeability and edema, restoration of endothelial adherens junctions, and reestablishment of the endothelial glycocalyx that is supported by plasma and platelets. Through understanding the complex interconnections between the development of TIC, vascular leak, and inflammation in EOT, improved diagnostics and relevant therapeutic targets can be determined.