Recombinant human soluble thrombomodulin administration improves sepsis-induced disseminated intravascular coagulation and mortality: a retrospective cohort study

Abstract

BackgroundEarly treatment of disseminated intravascular coagulation (DIC) can be associated with improved patient outcomes. The Japanese Ministry of Health and Welfare (JMHW) and the International Society on Thrombosis and Haemostasis (ISTH) criteria are the most specific for diagnosis of septic DIC. The revised Japanese Association for Acute Medicine (JAAM) criteria are able to diagnose sepsis-induced DIC in the early stage. Recombinant human soluble thrombomodulin (rhTM) has recently been used for treating DIC. Previous studies have shown a benefit of using rhTM for D,IC diagnosed by the JMHW or ISTH criteria, but not the JAAM criteria. The purpose of this study was to sequentially evaluate coagulation biomarkers and the DIC score after giving rhTM treatment to patients with sepsis-induced DIC diagnosed according to the JAAM criteria.MethodsWe performed a retrospective cohort study. Critically ill patients were included if diagnosed with sepsis-induced DIC according to the JAAM criteria. They were either treated without rhTM (control group) or with rhTM (treatment group). The primary outcome was the DIC score on day 7. The secondary outcome was 28-day mortality from the start of DIC treatment. Changes in the results of coagulation tests were assessed over time from the start of treatment to day 7.ResultsTwelve and 23 patients were assigned to the treatment and control groups, respectively. The DIC score on day 7 was significantly higher in the treatment group (3.3 ± 1.4) than in the control group (4.9 ± 1.8, p < 0.05). Estimated survival showed lower in treatment group than control group. There was significant difference between the control group and the treatment group (p < 0.05). The D-dimer level on day 7 was significantly lower in the treatment group (7.5 ± 4.1 μg/mL) than in the control group (30.9 ± 33.6 μg/mL, p < 0.05). Life-threatening bleeding did not occur. Our results indicated that rhTM improved sepsis-induced DIC and mortality.ConclusionsRecombinant human soluble thrombomodulin may improve sepsis-induced DIC diagnosed according to the JAAM criteria without an increased bleeding risk.

A retrospective comparative study of recombinant human thrombomodulin and gabexate mesilate in sepsis-induced disseminated intravascular coagulation patients

“…Another 2 retrospective studies of sepsis-induced DIC reported similar results [11,15]. In our study, the platelet counts had significantly improved by day 7 in the rhTM group, whereas a similar response was not observed in the GM group.…”

“…Several previous retrospective studies have reported that rhTM treatment yielded improved survival rates, compared with those in the control group without rhTM [9,11,15]. Although in this study the mortality of rhTM was similar to that of the GM group.…”

Administration of recombinant thrombomodulin before progression of disease causing disseminated intravascular coagulation might be better compared with administration after progression of disease

“…Recently, the safe use of rTM for ICU patients has been reported in a phase IIb study of rTM [3]. Another study had shown that rTM may be superior to conventional DIC treatments in patients in the ICU [4]. However, the optimal timing of rTM administration has not yet been determined.…”

Effects of longer use of recombinant human soluble thrombomodulin on outcomes of patients with disseminated intravascular coagulation based on a national administrative database

“…Treatment with rhs-TM has been reported to improve the prognosis of patients with sepsis-induced DIC without increasing bleeding risk 23) 24) , and administration of rhs-TM was found to reduce 28-day mortality rate in patients with DIC associated with severe sepsis 25) . These results show the efficacy of rhs-TM for patients with DIC associated with infectious diseases.…”