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

中文翻译：

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抗凝血酶和血栓调节蛋白联合治疗对脓毒症相关弥散性血管内凝血的影响：系统评价和荟萃分析

弥散性血管内凝血（DIC）综合征是一种高度致命的疾病，其特征是多器官损伤的并发症。尽管抗凝血酶 (AT) 和重组血栓调节蛋白 (rTM) 联合使用对 DIC 综合征的影响先前已被研究过，但结果不一致且不确定。因此，我们对 AT 和 rTM 联合用药治疗脓毒症 DIC 进行了系统评价，以使用随机效应分析模型研究联合疗法相对于 AT 或 rTM 单一疗法的优越性。我们检索了电子数据库，包括 Medline、Cochrane 对照试验中央注册库、Scopus 和 Igaku-Chuo Zasshi (ICHU-SHI) 日本中央医学评论网（从成立到 2022 年 1 月）。纳入了评估 AT 和 rTM 联合疗效的研究。主要结局是全因死亡率，次要结局是与单一疗法相比严重出血并发症的发生。我们根据每项主要研究的报告结果，提出了具有 95% 置信区间 (CI) 的汇总比值比 (OR) 或风险比 (HR)。我们分析了七项入组临床试验，所有这些都是观察性研究。与单一疗法相比，联合疗法与较低的 28 天死亡率没有显着的有利相关性（HR 0.67 [0.43–1.05]，OR 0.73 [0.45–1.18]）。I2 值分别为 60% 和 72%，表明异质性较高。作为次要结果，两组之间的出血并发症相似（合并 OR 1.11 [0.55–2.23]，I2 值 55%）。尽管本分析的结果无法证实 AT 和 rTM 联合治疗对脓毒症 DIC 具有统计学上的显着效果，但它在降低死亡率方面显示出有希望的效果。出血发生率低，临床可行。需要进一步的研究来得出更结论性的结果。这项研究已在大学医院医学信息网络 (UMIN) 临床试验注册中心注册 (UMIN ID: 000049820)。