Dual Targeting of NET Formation and Coagulation Improves Survival and Organ Protection in Experimental Sepsis

Combined administration of Cl-amidine and heparin provides a meaningful survival benefit and attenuates multi-organ injury in experimental sepsis. Although no statistically confirmed pharmacological synergy was observed across all parameters, the combined intervention exerted additive protective effects beyond single-agent treatment. Importantly, the additional histological protection could not be explained by further suppression of systemic cytokines or by changes in global coagulation parameters, and the underlying mechanisms therefore remain incompletely defined. Further preclinical studies addressing bleeding risk, optimal dosing strategies, and mechanistic pathways are warranted prior to clinical translation.