{"title":"抗凝血酶和凝血酶原联合疗法对败血症相关弥散性血管内凝血的影响:系统综述和荟萃分析","authors":"Takaaki Totoki, Yuto Makino, Kazuma Yamakawa, Hiroyuki Koami, Takeshi Wada, Takashi Ito, Toshiaki Iba","doi":"10.1186/s12959-023-00579-z","DOIUrl":null,"url":null,"abstract":"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. 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引用次数: 0
摘要
弥散性血管内凝血(DIC)综合征是一种高度致命的疾病,其特点是并发多器官损伤。虽然以前曾研究过抗凝血酶(AT)和重组血栓调节蛋白(rTM)联合应用对 DIC 综合征的影响,但结果并不一致,也没有定论。因此,我们对联合应用 AT 和 rTM 治疗脓毒症 DIC 进行了系统性综述,采用随机效应分析模型研究联合疗法优于 AT 或 rTM 单药疗法。我们检索了从开始到 2022 年 1 月的电子数据库,包括 Medline、Cochrane Central Register of Controlled Trials、Scopus 和 Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web。纳入的研究评估了AT和rTM联合治疗的疗效。与单一疗法相比,主要结果是全因死亡率,次要结果是严重出血并发症的发生率。根据每项主要研究的报告结果,我们列出了汇总的几率比(OR)或危险比(HR)及 95% 置信区间(CI)。我们分析了七项入选的临床试验,所有试验均为观察性研究。与单一疗法相比,联合疗法与较低的 28 天死亡率之间存在非显著的有利关联(HR 0.67 [0.43-1.05],OR 0.73 [0.45-1.18])。I2值分别为60%和72%,表明异质性很高。作为次要结果,两组的出血并发症相似(汇总 OR 1.11 [0.55-2.23],I2 值 55%)。虽然这项分析结果不能证实 AT 和 rTM 联合疗法对脓毒症 DIC 有统计学意义上的显著效果,但在改善死亡率方面却显示出良好的效果。出血发生率较低,临床上可行。要得出更确切的结果,还需要进一步研究。本研究已在大学医院医学信息网(UMIN)临床试验注册中心注册(UMIN ID:000049820)。
Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis
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).
期刊介绍:
Thrombosis Journal is an open-access journal that publishes original articles on aspects of clinical and basic research, new methodology, case reports and reviews in the areas of thrombosis.
Topics of particular interest include the diagnosis of arterial and venous thrombosis, new antithrombotic treatments, new developments in the understanding, diagnosis and treatments of atherosclerotic vessel disease, relations between haemostasis and vascular disease, hypertension, diabetes, immunology and obesity.