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. 2024 Jan 15;22(1):10.
doi: 10.1186/s12959-023-00579-z.

Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis

Takaaki Totoki  1 , Yuto Makino  2 , Kazuma Yamakawa  3 , Hiroyuki Koami  4 , Takeshi Wada  5 , Takashi Ito  6 , Toshiaki Iba  7
Affiliations

Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis

Takaaki Totoki et al. Thromb J. .

Abstract

Background: Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model.

Method: We searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study.

Results: We analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43-1.05], OR 0.73 [0.45-1.18]). The I2 values were 60% and 72%, respectively, suggesting high heterogeneity. As a secondary outcome, bleeding complications were similar between the two groups (pooled OR 1.11 [0.55-2.23], I2 value 55%).

Conclusions: Although the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results.

Trial registration: This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).

Keywords: Antithrombin; Disseminated intravascular coagulation; Sepsis; Thrombomodulin.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Preferred reporting items for systematic reviews and meta-analyses flow chart
Fig. 2
Fig. 2
Forest plot of random-effect analysis comparing mortality rates for combination therapy and monotherapy for septic DIC. A Integrated hazard ratio results. B: Integrated odds ratio results. Disseminated intravascular coagulation: DIC
Fig. 3
Fig. 3
Forest plot of random-effects analysis comparing bleeding complications of combination therapy versus monotherapy for septic DIC. Disseminated intravascular coagulation: DIC
See this image and copyright information in PMC

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