The role of platelets and neutrophil extracellular traps (NETs) in sepsis: A comprehensive literature review

Sepsis is defined as "an organic dysfunction secondary to the dysregulated response of the patient to an infection." This concept only reveals the tip of the iceberg, the clinical expression of organic failures, without understanding their basis, which is currently explained by cellular and molecular phenomena. Neutrophils are crucial pillars of early innate immune responses, and their fundamental function is phagocytosis. Additionally, neutrophils can degranulate upon activation, releasing various antimicrobial enzymes and pro-inflammatory cytokines, and form neutrophil extracellular traps (NETs), whose purpose is to trap pathogens by releasing their "sticky" nuclear content; the presence of activated platelets amplifies this phenomenon. NETosis is a beneficial process; however, deregulated, it can be detrimental, inducing "immunothrombosis" and compromising the microcirculation, thereby increasing the clinical severity of sepsis. The purpose of this review is to clearly describe the pathophysiological role therapeutic target of NETs, their interaction with platelets in sepsis, and their potential as therapeutic targets, since it has been shown that a therapeutic approach aimed at curbing NETs would be beneficial