DEVELOPMENT OF ENDOTHELIOPATHY: A SHARED HALLMARK ACROSS CRITICALLY ILL PATIENT POPULATIONS.

Abstract: Endotheliopathy has been increasingly recognized as a key feature of critical illness. Different diseases and syndromes manifest endothelial dysfunction in their severe forms. Septic syndrome, SARS-CoV-2 disease spectrum and cell therapy-associated toxicities represent paradigmatic examples of endotheliopathy, in intensive care units (ICU). As common features, and in response to the environment associated with these conditions, endothelial cells develop a pro-inflammatory and pro-thrombotic phenotype, switching its secretion behavior of anticoagulant and pro-fibrinolytic factors towards a hypercoagulative and hypofibrinolytic state. Intravascular microthrombi, release of neutrophil extracellular traps, detached endothelial cells and exposure of a highly reactive extracellular matrix towards platelets, result in turbulent blood flow and agglutination of circulating cells, ultimately leading to tissue hypoperfusion. Levels of endothelial damage biomarkers correlate with disease severity and, therefore, implementation of biomarkers panels could enhance prediction, differential diagnosis, and severity stratification in critical illness conditions. Development of strategies to protect the endothelium could mitigate pro-inflammatory and pro-coagulant responses, offering therapeutic potential for the endotheliopathy-associated conditions of critically ill patients.