Article Dans Une Revue Annals of Intensive Care Année : 2026

Physiopathology of fibrinolysis in sepsis-induced disseminated intravascular coagulation: Emerging mechanisms and pharmacological targets

Résumé

Septic shock represents the most severe form of an infection, marked by a dysregulated host response that can lead to multiple organ failure and death. Among these patients, 30-40% develop disseminated intravascular coagulation (DIC), a life-threatening complication associated with a 60% increase in mortality. DIC is characterized by widespread activation of the coagulation cascade, resulting in disseminated microthrombi and a hypercoagulable state. This prothrombotic profile arises from the upregulated expression of tissue factor by endothelial cells, monocytes, and neutrophils, combined with insufficient regulation by endogenous anticoagulant pathways. In addition, a profound impairment of fibrinolysis further contributes to this imbalance. Initially, this fibrinolytic insufficiency was attributed to elevated plasma levels of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor. More recently, it has been shown that DIC-associated fibrinolytic insufficiency during septic shock involves plasminogen degradation driven by neutrophil elastase carried by neutrophil extracellular traps circulating in patients' plasma.

The failure to resolve this hypercoagulable state and restore hemostatic balance has emerged as a key determinant of poor outcomes in DIC. Therefore, elucidating the mechanisms underlying fibrinolytic insufficiency is very important both to identify at-risk patients and to treat DIC.

This review provides an overview of the most recent advances in our understanding of fibrinolytic dysregulation in sepsis-induced DIC, with a particular focus on emerging molecular mechanisms and their implications for the identification of novel pharmacological targets.

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inserm-05464956 , version 1 (19-01-2026)

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Marine Tschirhart, Maeva Martin, Anaïs Curtiaud, Eduardo Angles-Cano, Ferhat Meziani, et al.. Physiopathology of fibrinolysis in sepsis-induced disseminated intravascular coagulation: Emerging mechanisms and pharmacological targets. Annals of Intensive Care, 2026, 16, pp.100008. ⟨10.1016/j.aicoj.2025.100008⟩. ⟨inserm-05464956⟩
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