Bastarache Julie A, Ware Lorraine B, Bernard Gordon R
Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Semin Respir Crit Care Med. 2006 Aug;27(4):365-76. doi: 10.1055/s-2006-948290.
Sepsis is a common and life-threatening condition with a high mortality rate. Severe sepsis includes multiorgan dysfunction syndrome. The organ most often affected is the lung, with development of acute lung injury (ALI), which, in its most severe form, is referred to as acute respiratory distress syndrome (ARDS). Our understanding of inflammation in the pathogenesis of sepsis and ALI is continually growing. However, therapies aimed at the inflammatory cascade in sepsis have been unsuccessful. These failures have led investigators to consider other pathways that may be important in the development of sepsis and ALI, including the coagulation and fibrinolytic cascades. In fact, the first therapy to reduce mortality in sepsis modulates the coagulation cascade. With this clinical success, administration of drotecogin alfa (recombinant activated protein C), the importance of coagulation in the pathogenesis of human sepsis is becoming clearer. This review summarizes the current understanding of the role of coagulation and fibrinolytic abnormalities in sepsis and the development of ALI and ARDS. Both in vitro and in vivo studies of the role of the coagulation cascade in sepsis and lung injury will be discussed, including initiation of coagulation through modulation of tissue factor and tissue factor pathway inhibitor, propagation of coagulation via protein C and thrombomodulin, inhibition of thrombin generation and resolution through thrombolysis by plasminogen activator, and plasminogen activator inhibitor-1.
脓毒症是一种常见且危及生命的疾病，死亡率很高。严重脓毒症包括多器官功能障碍综合征。最常受影响的器官是肺，会发展为急性肺损伤（ALI），其最严重的形式被称为急性呼吸窘迫综合征（ARDS）。我们对脓毒症和ALI发病机制中炎症的理解在不断加深。然而，针对脓毒症炎症级联反应的治疗并未成功。这些失败促使研究人员考虑其他可能在脓毒症和ALI发展中起重要作用的途径，包括凝血和纤溶级联反应。事实上，第一种降低脓毒症死亡率的治疗方法是调节凝血级联反应。随着重组活化蛋白C（drotrecogin alfa）在临床上的成功应用，凝血在人类脓毒症发病机制中的重要性日益明显。这篇综述总结了目前对凝血和纤溶异常在脓毒症以及ALI和ARDS发展中作用的理解。将讨论凝血级联反应在脓毒症和肺损伤中作用的体外和体内研究，包括通过调节组织因子和组织因子途径抑制剂启动凝血、通过蛋白C和血栓调节蛋白进行凝血传播、抑制凝血酶生成以及通过纤溶酶原激活剂进行溶栓和纤溶酶原激活剂抑制剂 -1来实现凝血溶解。
