Wang Ling, Bastarache Julie A, Ware Lorraine B
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Curr Pharm Des. 2008;14(19):1860-9. doi: 10.2174/138161208784980581.
Intravascular and extravascular fibrin formation are characteristic findings in patients with sepsis, suggesting that the activation of coagulation and the inhibiton of fibrinolysis are important in the pathogenesis of sepsis. Activation of coagulation during sepsis is primarily driven by the tissue factor (TF) pathway, while inhibition of fibrinolysis is primarily due to increases in plasminogen activator inhibitor -1(PAI-1). Downregulation of the anticoagulant Protein C pathway also plays an important role in the modulation of coagulation and inflammation in sepsis. Recent advances in the understanding of pathogenetic mechanisms of coagulation and fibrinolysis in sepsis may have therapeutic implications. Recombinant human activated protein C (rhAPC) is currently the only pharmacologic therapy that has been shown to reduce mortality in adults with severe sepsis, highlighting the importance of coagulation and fibrinolysis as a therapeutic target in sepsis. This review summarizes recent basic and clinical findings with regard to the role of the coagulation cascade in sepsis and explores potential therapeutic targets in the coagulation and fibrinolytic pathways in the management of sepsis.
血管内和血管外纤维蛋白形成是脓毒症患者的特征性表现，提示凝血激活和纤溶抑制在脓毒症发病机制中起重要作用。脓毒症期间的凝血激活主要由组织因子（TF）途径驱动，而纤溶抑制主要归因于纤溶酶原激活物抑制剂-1（PAI-1）增加。抗凝蛋白C途径的下调在脓毒症凝血和炎症调节中也起重要作用。脓毒症中凝血和纤溶发病机制认识的最新进展可能具有治疗意义。重组人活化蛋白C（rhAPC）是目前唯一已被证明可降低严重脓毒症成年患者死亡率的药物治疗，突出了凝血和纤溶作为脓毒症治疗靶点的重要性。本综述总结了关于凝血级联在脓毒症中作用的近期基础和临床研究结果，并探讨了脓毒症管理中凝血和纤溶途径的潜在治疗靶点。
