PATHOGENESIS OF DISSEMINATED INTRAVASCULAR COAGULATION IN SEPSIS
PATHOGENESIS OF DISSEMINATED INTRAVASCULAR COAGULATION IN SEPSIS
复制标题
DOI：
10.1001/jama.270.8.975
复制
发表时间：
1993-08-25
影响因子：
120.7
通讯作者：
VANDEVENTER, SJH
中科院分区：
文献类型：
--
作者：
LEVI, M;TENCATE, H;VANDEVENTER, SJH
目的：-综述脓毒症患者弥散性血管内凝血(DIC)发病机制的新见解，为治疗干预开辟新的方向。资料来源-关于脓毒症患者DIC发病机制的文章和发表的同行评议摘要。研究选择。-选择详细综述的研究，这些研究报道了有关败血症的人和动物模型中凝血和纤溶激活机制的细节。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的质量以及方法学方面的考虑，例如是否存在对照实验和统计分析。数据合成。-在循环中存在内毒素后，可以检测到显著的凝血激活。在这种激活之前，血清中各种细胞因子的水平都会增加，如肿瘤坏死因子和白介素类。抑制肿瘤坏死因子的增加会导致凝血活性的抑制。不同水平的凝血蛋白激活分子标志物的测定表明，凝血的激活是由组织因子依赖的途径介导的，这一点得到了实验的进一步证实，在实验中，抑制组织因子依赖的途径导致凝血活性的完全抑制。蛋白C-蛋白S抑制通路的功能受损似乎放大了凝血的激活作用。凝血和纤溶之间的失衡，最终导致纤溶酶原激活物抑制物1介导的纤溶抑制，可能进一步促进促凝血状态。结论：对脓毒症中凝血激活和纤溶的各种致病机制的了解增加可能具有治疗意义；然而，它们的有效性需要在适当的临床试验中进行评估。
Objective.-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.Data Sources.-Articles and published peer-reviewed abstracts on the mechanism of the initiation of DIC in sepsis.Study Selection.-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.Data Synthesis.-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.Conclusion.-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.