Zhang Ze, Yan Taotao, Ren Danfeng, Zhou Jingwen, Liu Liangru, Li Juan, Fu Shan, Ni Tianzhi, Xu Weicheng, Yang Yuan, Chen Tianyan, He Yingli, Zhao Yingren, Liu Jinfeng
The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Shaanxi Clinical Medical Research Center of Infectious Diseases, Xi'an, China.
Front Med (Lausanne). 2023 Jun 9;10:1157775. doi: 10.3389/fmed.2023.1157775. eCollection 2023.
Sepsis is a syndromic response to infection and is associated with high mortality, thus imposing a significant global burden of disease. Although low-molecular-weight heparin (LMWH) has been recommended to prevent venous thromboembolism, its anticoagulant and anti-inflammatory effects in sepsis remain controversial. Owing to the modification of the Sepsis-3 definition and diagnostic criteria, further evaluation of the efficacy and benefit population of LMWH is required.
We performed a retrospective cohort study to assess whether LMWH improved the inflammation, coagulopathy, and clinical outcomes against Sepsis-3 and to identify the target patients. All patients diagnosed with sepsis at the First Affiliated Hospital of Xi'an Jiaotong University (the largest general hospital in northwest China) from January 2016 to December 2020 were recruited and re-evaluated using Sepsis-3 criteria.
After 1:1 propensity score matching, 88 pairs of patients were categorized into the treatment and control groups based on subcutaneous LMWH administration. Compared with the control group, a significantly lower 28-day mortality was observed in the LMWH group (26.1 vs. 42.0%, = 0.026) with a comparable incidence of major bleeding events (6.8 vs. 8.0%, = 0.773). Cox regression analysis showed that LMWH administration was the independent protective factor for septic patients (aHR, 0.48; 95% CI, 0.29-0.81; = 0.006). Correspondingly, the LMWH treatment group showed a significant improvement in inflammation and coagulopathy. Further subgroup analysis showed that LMWH therapy was associated with favorable outcomes in patients younger than 60 years and diagnosed with sepsis-induced coagulopathy (SIC), ISTH overt DIC, non-septic shock, or non-diabetics and in patients included in the moderate-risk group (APACHE II score 20-35 or SOFA score 8-12).
Our study results showed that LMWH improves 28-day mortality by improving inflammatory response and coagulopathy in patients meeting Sepsis-3 criteria. The SIC and ISTH overt DIC scoring systems can better identify septic patients who are likely to benefit more from LMWH administration.
脓毒症是对感染的一种综合征反应,与高死亡率相关,因此给全球带来了重大的疾病负担。尽管低分子量肝素(LMWH)已被推荐用于预防静脉血栓栓塞,但其在脓毒症中的抗凝和抗炎作用仍存在争议。由于脓毒症-3定义和诊断标准的修订,需要对LMWH的疗效和受益人群进行进一步评估。
我们进行了一项回顾性队列研究,以评估LMWH是否能改善针对脓毒症-3的炎症、凝血病和临床结局,并确定目标患者。招募了2016年1月至2020年12月在西安交通大学第一附属医院(中国西北最大的综合医院)被诊断为脓毒症的所有患者,并使用脓毒症-3标准进行重新评估。
经过1:1倾向评分匹配后,根据皮下注射LMWH将88对患者分为治疗组和对照组。与对照组相比,LMWH组的28天死亡率显著降低(26.1%对42.0%,P = 0.026),主要出血事件的发生率相当(6.8%对8.0%,P = 0.773)。Cox回归分析表明,给予LMWH是脓毒症患者的独立保护因素(风险比,0.48;95%置信区间,0.29 - 0.81;P = 0.006)。相应地,LMWH治疗组在炎症和凝血病方面有显著改善。进一步的亚组分析表明,LMWH治疗在年龄小于60岁、诊断为脓毒症诱导的凝血病(SIC)、国际血栓与止血学会显性弥散性血管内凝血(ISTH overt DIC)、非脓毒性休克或非糖尿病患者以及中度风险组(急性生理与慢性健康状况评分II 20 - 35或序贯器官衰竭评估评分8 - 12)的患者中与良好结局相关。
我们的研究结果表明,LMWH通过改善符合脓毒症-3标准患者的炎症反应和凝血病来提高28天死亡率。SIC和ISTH显性DIC评分系统可以更好地识别可能从LMWH给药中获益更多的脓毒症患者。