Coagulofibrinolytic changes in patients with disseminated intravascular coagulation associated with post-cardiac arrest syndrome--fibrinolytic shutdown and insufficient activation of fibrinolysis lead to organ dysfunction

Abstract

Introduction: Post-cardiac arrest syndrome (PCAS) is often associated with disseminated intravascular coagulation (DIC), thus leading to the development of multiple organ dysfunction syndrome (MODS). The aim of this study was to examine the pathophysiological relationships between coagulation, fibrinolysis and fibrinolytic shutdown by evaluating the levels of coagulofibrinolytic markers, including soluble fibrin, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC), plasmin-alpha2 plasmin inhibitor complex (PPIC), neutrophil elastase and fibrin degradation product by neutrophil elastase (EXDP).

Materials and methods: Fifty-two resuscitated patients were divided into two groups: 22 DIC and 30 non-DIC patients.

Results: The levels of soluble fibrin, PPIC, tPAIC, EXDP and neutrophil elastase in the DIC patients with PCAS were significantly higher than those observed in the non-DIC patients. The values of the tPAIC and JAAM DIC scores were found to be independent predictors of increased SOFA scores in the DIC patients. The MODS patients demonstrated significantly higher levels of soluble fibrin and tPAIC; however, the levels of TAFI and EXDP were identical between the patients with and without MODS. In addition, positive correlations were observed between the levels of tPAIC and EXDP in the patients with non-MODS; however, no correlations were observed between these markers in the MODS patients.

Conclusions: Thrombin activation and fibrinolytic shutdown play important roles in the development of organ dysfunction in PCAS patients. Neutrophil elastase-mediated fibrinolysis cannot overcome the fibrinolytic shutdown that occurs in DIC patients with PCAS, thus resulting in the development of MODS.

Keywords: APACHE; Acute Physiology and Chronic Health Evaluation; DIC; EXDP; FDP; JAAM; Japanese Association for Acute Medicine; MODS; PAI-1; PCAS; PPIC; ROSC; SOFA; Sequential Organ Failure Assessment; TAFI; disseminated intravascular coagulation; disseminated intravascular coagulation (DIC); fibrin degradation product by neutrophil elastase; fibrin/fibrinogen degradation product; fibrinolytic shutdown; imbalance between coagulation and fibrinolysis; multiple organ dysfunction syndrome; organ dysfunction; plasmin-alpha2 plasmin inhibitor complex; plasminogen activator inhibitor-1; post-cardiac arrest syndrome; return of spontaneous circulation; t-PA; tPAIC; thrombin-activatable fibrinolytsis inhibitor; tissue plasminogen activator; tissue-type plasminogen activator-plasminogen activator inhibitor-1 complex.