• Chavi Rehani, Sarah Abdullah, and Rosemary Ann Kozar.
• Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
• Curr Opin Crit Care. 2025 Jan 6.

Purpose Of ReviewThis review aims to examine recent advances in the understanding of injury-induced endotheliopathy and therapeutics to mitigate its development in critically injured patients.Recent FindingsClinical studies have clearly demonstrated that syndecan-1 ectodomains can be found in circulation after various types of trauma and injury and correlates with worse outcomes. As the mechanisms of endotheliopathy are better understood, pathologic hyperadhesive forms of von Willebrand factor, along with a relative deficiency of its cleaving enzyme, a disintegrin and metalloprotease with thrombospondin type I motifs, member 13 (ADAMTS13), have emerged as additional biomarkers. Therapeutics to date have focused primarily on the protective effects of fresh frozen plasma and its constituents to restore the glycocalyx. Human recombinant ADAMTS13 holds promise, as do synthetic variants of heparan sulfate and activated protein C, although all data to date are preclinical.SummaryInjury-induced endotheliopathy represents an important pathologic response to trauma. Key biomarkers, such as syndecan-1, can aid in the diagnosis, but testing is not yet available clinically. As the mechanisms of endotheliopathy are better understood, therapeutics are being identified and show promise. To date, plasma has been the most widely studied; however, like all therapeutics for injury-induced endotheliopathy, it has primarily been studied in the preclinical setting.Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.

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