Acetylsalicylic acid inhibits intravascular coagulation during Staphylococcus aureus–induced sepsis in mice

• Published in: Blood 2020-04, Vol.135 (15), p.1281-1286
• Main Authors: Carestia, Agostina, Davis, Rachelle P., Grosjean, Heidi, Lau, Matthew W., Jenne, Craig N.
• Format: Article
• Language: English
• Subjects: Animals; Aspirin - therapeutic use; Blood Coagulation - drug effects; Disseminated Intravascular Coagulation - blood; Disseminated Intravascular Coagulation - etiology; Disseminated Intravascular Coagulation - prevention & control; Mice; Mice, Inbred C57BL; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - therapeutic use; Sepsis - blood; Sepsis - complications; Staphylococcal Infections - blood; Staphylococcal Infections - complications; Staphylococcus aureus - physiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2019002783

Antiplatelet therapies have been proposed for the treatment of sepsis, a syndrome resulting from a dysregulated immune response and inappropriate activation of coagulation. Acetylsalicylic acid (ASA) may serve as a potential therapeutic strategy to prevent infection-induced coagulopathy and associated tissue damage. Using intravital microscopy, we found that Staphylococcus aureus infection induced neutrophil recruitment, platelet aggregation, and neutrophil extracellular trap (NET) release in the liver. Mice pretreated with ASA, or animals receiving ASA 3 hours postinfection, had significantly reduced platelet aggregation and NET release. Additionally, ASA-treated mice had reduced intravascular thrombin activity and microvascular occlusion as compared with untreated S aureus–infected mice. This inhibition of coagulation was accompanied by decreased levels of alanine aminotransferase and aspartate aminotransferase in the plasma, indicating less liver damage. Finally, bacterial loads (colony-forming units per milliliter) in liver, lung, and spleen were not different between groups, and the phagocytic capacity of Kupffer cells was preserved following ASA treatment. These results suggest that ASA may serve as a therapeutic approach to sepsis through its ability to reduce the deleterious action of immunothrombi while maintaining innate immune functions. •ASA prevents infection-induced coagulopathy, improves microvascular perfusion, and reduces tissue damage while preserving immune response. [Display omitted]