Human Soluble Recombinant Thrombomodulin, ART-123, Resolved Early Phase Coagulopathies, but Did Not Significantly Alter the 28 Day Outcome in the Treatment of DIC Associated with Infectious Systemic Inflammatory Response Syndromes.

Shusuke Mori,Yasuhiro Otomo,Toshiki Sera,Kanae Ochiai,Tomohiko Ai

doi:10.3390/jcm8101553

Abstract

Disseminated intravascular coagulation (DIC) is a catastrophic systemic disorder of coagulation, resulting in uncontrollable bleeding, multiple organ failure, and death. Sepsis is one of the common causes of DIC. Despite many attempts to correct these coagulation pathologies, no adjunctive treatments have been shown to improve the mortality of DIC associated with sepsis. Although some clinical studies showed a recently developed human recombinant thrombomodulin, ART-123, might be effective in the treatment of DIC, few randomized, placebo-controlled studies have been conducted. In this study, we treated 60 DIC patients associated with systemic inflammatory response syndrome (SIRS) using ART-123 (n = 29) or saline as a placebo (n = 31). The basal clinical characteristics were similar in both groups. We compared clinical severity scores and DIC score in acute phase, and 28 day mortality between the two groups. Our study demonstrated the DIC score improved a few days earlier in the ART-123 group than the placebo group, and there were no major life-threatening adverse events in both groups. The overall survival rate at day 28 was not significantly altered. In conclusion, ART-123 can be used safely in DIC associated with infectious SIRS patients; however, its true efficacy in the treatment of DIC needs to be further investigated.

Highlights

Disseminated intravascular coagulation (DIC) is a catastrophic systemic disorder of coagulation, resulting in uncontrollable bleeding, multiple organ failure (MOF) and death
Patients’ demographics and medical conditions on admission were comparable between ART-123 and the control groups: APACHE II [21], SOFA [22], and JAAM DIC scores [16]
This study is one of the few prospective, randomized, placebo-controlled studies to investigate the effects of human recombinant thrombomodulin, ART-123, in the treatment of DIC associated with infectious systemic inflammatory response syndrome (SIRS)

Summary

Introduction

Disseminated intravascular coagulation (DIC) is a catastrophic systemic disorder of coagulation, resulting in uncontrollable bleeding, multiple organ failure (MOF) and death. It can be caused by various medical conditions including sepsis, trauma, cancers, obstetrical complications, vascular disorders, toxins, immunologic disorders, and inflammations [1]. International and Japanese guidelines for the treatment of DIC state that treatment of underlying diseases is the most effective way to reverse this catastrophic coagulation disorder [4,5,6]. There are some discrepancies between the Japanese DIC management guidelines and other guidelines mainly regarding supportive adjunctive treatments aiming at coagulation disorders. Activated protein C plays an important role in suppressing coagulation and inflammatory systems [8]

Methods

Results

Discussion

Conclusion