Levi M, ten Cate H, van der Poll T, van Deventer S J
Center for Haemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands.
JAMA. 1993 Aug 25;270(8):975-9.
To review new insights in the pathogenetic mechanisms involved in the development of disseminated intravascular coagulation (DIC) in septic patients, in order to develop new directions for therapeutic intervention.
Articles and published peer-reviewed abstracts on the mechanism of the initiation of DIC in sepsis.
Studies selected for detailed review were those reporting specifics about the mechanism of activation of coagulation and fibrinolysis in experimental human and animal models of sepsis. Data extraction guidelines for assessing data quality included validity of the model, quality of the laboratory assessment of activation of coagulation and fibrinolysis, and methodological considerations, such as the presence of control experiments and statistical analysis.
After the presence of endotoxin in the circulation, significant coagulation activation can be detected. This activation is preceded by an increase in the serum levels of various cytokines, such as tumor necrosis factor and interleukins. Inhibition of the increase in tumor necrosis factor results in inhibition of coagulation activation. Measurement of molecular markers for the activation of coagulation proteins at various levels indicates that the activation of coagulation is mediated by the tissue factor-dependent pathway, which is further confirmed by experiments in which the inhibition of the tissue factor-dependent pathway resulted in complete inhibition of coagulation activation. The activation of coagulation seems to be amplified by impaired function of the protein C-protein S inhibitory pathway. An imbalance between coagulation and fibrinolysis, ultimately leading to plasminogen activator inhibitor type 1-mediated inhibition of fibrinolysis, may further promote the procoagulant state.
The increased knowledge of the various pathogenetic mechanisms of coagulation activation and fibrinolysis in sepsis may have therapeutic implications; however, their efficacy needs to be assessed in appropriate clinical trials.
回顾脓毒症患者弥散性血管内凝血（DIC）发病机制的新见解，以便为治疗干预开辟新方向。
关于脓毒症中DIC起始机制的文章及已发表的经同行评审的摘要。
入选进行详细综述的研究是那些报告脓毒症实验性人类和动物模型中凝血和纤溶激活机制具体情况的研究。评估数据质量的数据提取指南包括模型的有效性、凝血和纤溶激活的实验室评估质量以及方法学考量，如是否存在对照实验和统计分析。
循环中出现内毒素后，可检测到显著的凝血激活。这种激活之前是多种细胞因子血清水平的升高，如肿瘤坏死因子和白细胞介素。抑制肿瘤坏死因子的升高会导致凝血激活受到抑制。对各级凝血蛋白激活的分子标志物进行测量表明，凝血激活由组织因子依赖途径介导，这在抑制组织因子依赖途径导致凝血激活完全受抑制的实验中得到进一步证实。凝血激活似乎因蛋白C - 蛋白S抑制途径功能受损而被放大。凝血与纤溶之间的失衡，最终导致纤溶酶原激活物抑制剂1介导的纤溶抑制，可能会进一步促进促凝状态。
对脓毒症中凝血激活和纤溶各种发病机制的深入了解可能具有治疗意义；然而，其疗效需要在适当的临床试验中进行评估。
