Abstract

BackgroundClinical evidence showing the effectiveness of recombinant human soluble thrombomodulin (rhTM) for treating sepsis-induced disseminated intravascular coagulation (DIC) and organ dysfunction (particularly renal injury) is limited because of differences in the inclusion criteria and disease severity among patients. This study aimed to assess the association between rhTM and outcomes in septic DIC patients with acute kidney injury (AKI).MethodsThis retrospective observational study analyzed the data of patients who were admitted to the intensive care unit (ICU) of a single center between January 2012 and December 2018, and diagnosed with sepsis-induced DIC and AKI. Data were extracted as follows: patients’ characteristics; DIC score, as calculated by the Japanese Association for Acute Medicine and the International Society of Thrombosis and Hemostasis criteria; serum creatinine levels; and ICU and 28-day mortality rates. The primary outcome was the dependence on renal replacement therapy (RRT) at ICU discharge. The propensity score (PS) was calculated using the following variables: age, sex, septic shock at admission, DIC score, and KDIGO classification. Subsequently, logistic regression analysis was performed using the PS to evaluate the outcome.ResultsIn total, 97 patients were included in this study. Of these, 52 (53.6%) patients had received rhTM. The dependence on RRT at ICU discharge was significantly lower in the rhTM than in the non-rhTM group (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.19–0.97; P = 0.043). The serum creatinine levels at ICU discharge (OR, 0.31; 95% CI, 0.13–0.72; P = 0.007) and hospital discharge (OR, 0.25; 95% CI, 0.11–0.60; P = 0.002, respectively), and the 28-day mortality rate (OR, 0.40; 95% CI, 0.17–0.93; P = 0.033) were significantly lower in the rhTM than in the non-rhTM group. Moreover, the Kaplan–Meier survival curve revealed significantly lower mortality rates in the rhTM than in the non-rhTM group (P = 0.009). No significant differences in the DIC score and AKI severity were observed between the groups.ConclusionsAmong sepsis-induced DIC patients with AKI, rhTM administration was associated with lower dependence on RRT at ICU discharge, improvement in renal function, and lower 28-day mortality rate.

Highlights

  • Clinical evidence showing the effectiveness of recombinant human soluble thrombomodulin for treating sepsis-induced disseminated intravascular coagulation (DIC) and organ dysfunction is limited because of differences in the inclusion criteria and disease severity among patients

  • Among sepsis-induced DIC patients with acute kidney injury (AKI), recombinant human soluble thrombomodulin (rhTM) administration was associated with lower dependence on renal replacement therapy (RRT) at intensive care unit (ICU) discharge, improvement in renal function, and lower 28-day mortality rate

  • Patients were diagnosed with sepsis and DIC at ICU admission according to the SEPSIS-3 definition [17] and the DIC criteria established by the Japanese Association for Acute Medicine (JAAM) [18], respectively

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Summary

Introduction

Clinical evidence showing the effectiveness of recombinant human soluble thrombomodulin (rhTM) for treating sepsis-induced disseminated intravascular coagulation (DIC) and organ dysfunction ( renal injury) is limited because of differences in the inclusion criteria and disease severity among patients. This study aimed to assess the association between rhTM and outcomes in septic DIC patients with acute kidney injury (AKI). Despite advances in modern medicine, sepsis and septic shock remain the leading causes of death in critically ill patients [1,2,3]. Large amounts of inflammatory mediators are produced during sepsis, inducing endothelial cell perturbation and resulting in coagulopathy and disseminated intravascular coagulation (DIC). Endothelial perturbation was reported to be responsible for the sepsis-induced organ failure development [7]

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