Background: Endothelial dysfunction plays a key role in sepsis physiopathology, leading to multiorgan failure and death. Defibrotide (DF) is a product effective in the protection of endothelial cells (ECs). Although the mechanism of action of this drug is uncertain, it may have a role as potential treatment for sepsis complications.
Aims: Characterizein-vitrothe activation and damage of ECs in different sepsis syndrome and determine the influence of DF in these alterations.
Methods: Humanumbilical vein endothelial cells (HUVEC) were grown in the presence of 20% pooled sera collected from patients with septic syndrome (sepsis, severe sepsis and septic shock) or systemic inflammatory response syndrome (SIRS) within the first 24 hours of symptoms onset. Sera from healthy volunteers was used as control. We assessed changes in the expression of ECs receptors (ICAM-1 and VCAM-1), the presence of extracellular adhesive proteins such a Von Willebrand factor (VWF) and the thrombogenicity of the extracellular matrix (ECM) generated by these cells. To explore the effect of DF, ECs were incubated with DF (100 µg/mL) for 24 hours before being exposed to the sera and every 24 hours after the exposition.
Results: EC activation, determined by an increase in expression of ICAM-1 and VCAM-1 and an increase in expression of VWF and platelet adhesion on the ECM, was higher in septic syndrome compared with SIRS and control group (p< 0.001) with a progressive increase correlated with sepsis severity (sepsis < severe sepsis ≤ septic shock) (p< 0.05 for VCAM-1, ICAM-1 and VWF; p< 0.001 for platelet adhesion). Previous exposure and continuous incubation of ECs with DF modified the endothelial response by significantly reducing VWF, ICAM-1, VCAM-1 and platelet adhesion induced by sera from patients with septic syndrome in all gropus (p< 0.001).
Conclusions: DF prevents activation and endothelial damage induced in septic syndrome in an in-vitromodel of sepsis.
To cite this abstract in AMA style:
Palomo M, Fernandez S, Molina P, Aibar J, Nicolas J, Castro P, Diaz-Ricart M. Defibrotide Prevents Sepsis Induced Endothelial Cell Activation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/defibrotide-prevents-sepsis-induced-endothelial-cell-activation/. Accessed November 26, 2020.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/defibrotide-prevents-sepsis-induced-endothelial-cell-activation/