A low TAFI activity and insufficient activation of fibrinolysis by both plasmin and neutrophil elastase promote organ dysfunction in disseminated intravascular coagulation associated with sepsis

Abstract

IntroductionWe hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and the activation of fibrinolysis by both plasmin and neutrophil elastase is insufficient to overcome fibrinolytic shutdown, contributing to multiple organ dysfunction syndrome (MODS) in sepsis-induced disseminated intravascular coagulation (DIC). Materials and MethodsFifty patients with sepsis were prospectively enrolled. The DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC and the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. ResultsThe JAAM DIC scores were independent predictors of patient death and MODS. The JAAM DIC patients, especially those who met the ISTH overt DIC criteria, showed lower TAFI activity, and higher levels of soluble fibrin, neutrophil elastase, fibrin degradation product by neutrophil elastase (EXDP), plasmin-alpha2 plasmin inhibitor complex (PPIC), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC) and D-dimer in comparison with non-DIC patients. There were differences in the levels of soluble fibrin, tPAIC, TAFI activity, and neutrophil elastase between the patients with and without MODS. However, no differences were observed in the levels of PPIC, D-dimer, or EXDP. Soluble fibrin negatively correlated with the TAFI activity. High neutrophil elastase, low TAFI activity and PPIC are independent predictors of patient death and MODS. tPAIC is an independent predictor of elevation of EXDP in DIC patients. ConclusionsActivation of fibrinolysis both by plasmin and neutrophil elastase cannot overcome fibrinolytic shutdown, leading to MODS and a poor outcome in sepsis-induced DIC. The systemic activation of neutrophils and a low TAFI activity are also involved in the pathogenesis of MODS.