Yu Sihan, Chi Yawen, Ma Xiaochun, Li Xu
Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Front Immunol. 2024 Dec 6;15:1495260. doi: 10.3389/fimmu.2024.1495260. eCollection 2024.
Sepsis is a clinical syndrome resulting from the interaction between coagulation, inflammation, immunity and other systems. Coagulation activation is an initial factor for sepsis to develop into multiple organ dysfunction. Therefore, anticoagulant therapy may be beneficial for sepsis patients. Heparin possesses a variety of biological activities, so it has a broad prospect in sepsis. Previous studies suggested that patients with sepsis-induced disseminated intravascular coagulation and high disease severity might be suitable for anticoagulant therapy. With the development of artificial intelligence (AI), recent studies have shown that patients with severe coagulation activation represent the targeted patients for anticoagulant therapy in sepsis. However, it remains necessary to accurately define the relevant biomarkers indicative of this phenotype and validate their clinical utility by large randomized controlled trials (RCTs). Analyses of data from early small RCTs, subgroup analyses of large RCTs and meta-analyses have collectively suggested that anticoagulant therapy, particularly the use of heparin, may be an effective approach for managing sepsis patients. Concurrently, debate persists regarding the optimal selection of anticoagulants, proper timing, usage and dosage of administration that should be employed to assess treatment efficacy. The primary mechanisms of heparin are acting on heparan sulfate, histones, high mobility group box 1 and heparin-binding protein, which interfere with the regulation of inflammation, vascular permeability, coagulation, endothelial function and other biological activities. However, the underlying pathophysiological processes mediating the potential therapeutic effects of heparin in the context of sepsis remain incompletely understood and warrant additional rigorous investigation to establish the mechanism more conclusively.
脓毒症是一种由凝血、炎症、免疫等系统相互作用引起的临床综合征。凝血激活是脓毒症发展为多器官功能障碍的初始因素。因此，抗凝治疗可能对脓毒症患者有益。肝素具有多种生物学活性，因此在脓毒症治疗方面具有广阔前景。以往研究表明，脓毒症诱导的弥散性血管内凝血患者及疾病严重程度高的患者可能适合抗凝治疗。随着人工智能（AI）的发展，近期研究表明，凝血激活严重的患者是脓毒症抗凝治疗的目标人群。然而，仍有必要准确界定指示该表型的相关生物标志物，并通过大型随机对照试验（RCT）验证其临床效用。早期小型RCT数据的分析、大型RCT的亚组分析和荟萃分析共同表明，抗凝治疗，尤其是肝素的使用，可能是治疗脓毒症患者的有效方法。同时，关于抗凝剂的最佳选择、评估治疗效果时应采用的适当给药时机、用法和剂量，仍存在争议。肝素的主要作用机制是作用于硫酸乙酰肝素、组蛋白、高迁移率族蛋白盒1和肝素结合蛋白，从而干扰炎症、血管通透性、凝血、内皮功能及其他生物活性的调节。然而，肝素在脓毒症背景下潜在治疗作用的潜在病理生理过程仍未完全明了，需要进行更多严格研究以更确凿地确定其机制。
