# Safety of Recombinant Thrombomodulin for Severe Gastroenterological Sepsis-Induced Coagulopathy in Patients Undergoing Invasive Digestive Procedures: A Single-Center Retrospective Cohort Study

## TL;DR

This study shows that recombinant thrombomodulin (rTM) is safe and effective for treating severe coagulopathy in digestive sepsis patients, even those needing invasive procedures.

## Contribution

The study provides novel evidence on the safety of rTM in septic DIC patients undergoing invasive digestive procedures.

## Key findings

- rTM improved DIC scores significantly without increasing bleeding complications.
- Survival rate was 78.7% with no significant difference between groups requiring invasive procedures and those that did not.
- Mortality was influenced by post-rTM DIC scores and performance status, not by invasive procedures.

## Abstract

Introduction

Several studies demonstrated that anticoagulant treatment, including the administration of recombinant human soluble thrombomodulin (rTM), could improve the outcomes of patients with gastroenterological sepsis-induced disseminated intravascular coagulation (DIC). However, there is little evidence on the safety of rTM administration for septic DIC requiring invasive procedures (IPs). In the current study, we assessed the safety and efficacy of rTM in patients with sepsis-induced DIC associated with digestive diseases.

Methods

The current retrospective cohort study included 155 cases in which rTM was administered for septic DIC associated with digestive diseases at our hospital between 2014 and 2023. The subjects were divided into an IP group (n = 102) and a non-IP group (n = 53), and background factors, the presence or absence of rTM-related complications, and mortality were compared between the groups.

Results

CHADS2 and CHA2DS2-VASc scores were similar between the groups, although the Sequential Organ Failure Assessment (SOFA) score was significantly higher in the IP group than in the non-IP group (5 vs. 3, p = 0.008). The IP group had significantly more patients taking oral antithrombotic (61% (62/102) vs 43% (23/53), p = 0.043) and more cases at high risk of bleeding with a HAS-BLED score of 3 or higher (70% (71/102) vs 43% (25/53), p = 0.009) than the non-IP group. The rTM was administered for a median of six days, and the DIC scores significantly improved from 5.5 to 2.9 points after rTM administration (p < 0.0001). The rTM-related bleeding complications were observed in nine cases (5.8%), and the overall survival rate was 78.7% (122/155), with no significant difference between the groups. Multivariate analysis revealed that the factors influencing mortality were the DIC score after rTM administration (p = 0.006) and performance status (p = 0.017), but not the presence or absence of IPs.

Conclusion

Septic DIC associated with digestive system diseases is a pathological condition with a poor prognosis, but rTM administration improved DIC without increasing bleeding complications, regardless of the presence or absence of IPs. Administration of rTM might be safe and does not increase bleeding complications, even in high-risk patients requiring IPs.