Thromboinflammation in Sepsis and Heparin: A Review of Literature and Pathophysiology.

ABSTRACT

BACKGROUND/AIM: Thromboinflammation is the pathophysiologic mechanism in which coagulation and inflammation interact and complement each other. It is observed in a number of degenerative diseases, one of them being sepsis. Quiescent endothelial cells exert antithrombotic and anti-inflammatory actions that are reduced during sepsis. The concomitant effect of the subsequent dysregulation of coagulation and complement actuation is platelet activation and aggregation, and leukocyte recruitment, with detrimental effects on the vascular endothelium. Tissue factor and α-thrombin are major sentinels in the pathogenesis of this process. This literature review aimed to cover the basic principles of the mechanisms implicated in thromboinflammation occurring during sepsis and also investigates the role of heparin as a possible therapeutic agent, since it exhibits both anticoagulant and anti-inflammatory functions. MATERIALS AND METHODS: PubMed, SCOPUS and ScienceDirect databases were used for search of literature from inception to April 2022. To be included in our review, studies had to refer to the pathophysiologic mechanisms leading to coincident coagulation and inflammation, or to the administration of heparin either for treatment or prophylaxis, both in the context of sepsis. RESULTS: A total of 276 articles were drawn from the initial literature search. 124 were duplicated and out of the remaining 152 articles, 29 met our inclusion criteria and were reviewed. CONCLUSION: Clinical trials among sepsis patients have indicated that the thromboinflammatory process is more complex than believed, as adverse bleeding events continue to occur despite the use of anticoagulants with different pharmacodynamics. However, heparin has a pleiotropic effect that might provide protection against sepsis and related complications and merits further research.