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. 2025 Mar 14;17(3):e80589.
doi: 10.7759/cureus.80589. eCollection 2025 Mar.

Efficacy and Safety of Recombinant Human Soluble Thrombomodulin in Patients With Sepsis-Induced Disseminated Intravascular Coagulation After Emergency Surgery

Keiji Nagata  1 , Takahisa Fujikawa  1 , Taisuke Matsuoka  1
Affiliations

Efficacy and Safety of Recombinant Human Soluble Thrombomodulin in Patients With Sepsis-Induced Disseminated Intravascular Coagulation After Emergency Surgery

Keiji Nagata et al. Cureus. .

Abstract

Introduction Recombinant human soluble thrombomodulin (rhsTM) is a therapeutic agent for sepsis-induced disseminated intravascular coagulation (DIC) and is reported to be associated with bleeding events. Although several studies on rhsTM have been reported, the safety and efficacy of rhsTM for sepsis-induced DIC after emergency laparotomy remain controversial. In this study, we aimed to investigate the efficacy, safety, and bleeding complications of rhsTM in patients with sepsis-induced DIC following emergency abdominal surgery. Methods In this retrospective observational study, we reviewed the data of patients who underwent emergency surgery for gastrointestinal necrosis and perforation and received rhsTM for sepsis-induced DIC at a single center between January 2014 and December 2023. We evaluated the incidence rate of bleeding complications associated with rhsTM treatment, clinical characteristics, and changes in Japanese Association for Acute Medicine (JAAM) DIC scores. Patients with DIC were identified as having the JAAM DIC diagnostic criteria (DIC score ≥4). Results We analyzed a total of 32 patients with sepsis-induced DIC. The APACHE II (Acute Physiology and Chronic Health Evaluation II) score at admission to the intensive care unit was 20. A total of 46.9% of the patients had poor renal function with CKD (chronic kidney disease), classified based on KDIGO (Kidney Disease: Improving Global Outcomes) stage 4 or higher, and 37.5% were on regular hemodialysis. A total of 59.4% of the patients received antithrombotic therapy. The JAAM DIC score was significantly ameliorated from the first day of rhsTM administration (5.3) to days 5-7 of rhsTM administration (3.3) (p < 0.0001). A total of 75% of the patients had a HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Use) score, an indicator of bleeding risk, of 3 or higher. The mortality rate in the whole cohort was 37.5%. Patients were also classified into the following groups: HAS-BLED score ≥3 (n = 24) and <3 (n = 8), and survivors (n = 20) and non-survivors (n = 12). No perioperative bleeding complications were observed. Conclusion rhsTM was not associated with an increased incidence of bleeding complications, even in patients with sepsis-induced DIC following emergency abdominal surgery and in critically ill patients with poor renal function or those receiving antithrombotic therapy. rhsTM is a safe and effective anticoagulant for the management of sepsis-induced DIC after emergency surgery and is clinically feasible.

Keywords: anticoagulant therapy; disseminated intravascular coagulation (dic); japanese association for acute medicine (jaam) dic scores; recombinant human soluble thrombomodulin (rhstm); sepsis.

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Conflict of interest statement

Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Kokura Memorial Hospital Clinical Research Ethics Committee issued approval 19101604. The study protocol adhered to the principles outlined in the Declaration of Helsinki and received approval (#19101604) from the Kokura Memorial Hospital Clinical Research Ethics Committee. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Flowchart and treatment strategy for peritonitis associated with gastrointestinal necrosis or perforation and sepsis-induced DIC
*A dose of rhsTM was decreased (130 U/kg/day) in cases of severe renal dysfunction. DIC: disseminated intravascular coagulation, JAAM: Japanese Association for Acute Medicine, SIRS: systemic inflammatory response syndrome, AT: antithrombin, Plt: platelet, PT: prothrombin, FDP: fibrin/fibrinogen degradation products.
Figure 2
Figure 2. Changes of JAAM DIC score after the initiation of rhsTM therapy in all patients (n= 32)
The number in the middle of each boxplot is the median value. JAAM: Japanese Association for Acute Medicine, DIC: disseminated intravascular coagulation, rhsTM: recombinant human soluble thrombomodulin.
Figure 3
Figure 3. Changes in the JAAM DIC score after the initiation of rhsTM therapy in patients with a HAS-BLED score (≥3) (n = 24) and a HAS-BLED score (<3) (n = 8).
The number in the middle of each boxplot is the median value. JAAM: Japanese Association for Acute Medicine, DIC: disseminated intravascular coagulation, rhsTM: recombinant human soluble thrombomodulin.
Figure 4
Figure 4. Changes in the JAAM DIC score after the initiation of rhsTM therapy in survivors (n = 20) and non-survivors (n = 12)
The number in the middle of each boxplot is the median value. JAAM: Japanese Association for Acute Medicine, DIC: disseminated intravascular coagulation, rhsTM: recombinant human soluble thrombomodulin.
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