Ware Lorraine B, Bastarache Julie A, Wang Ling
Division of Allergy, Pulmonary, and Critical Care, Department of Medicine Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA.
Keio J Med. 2005 Sep;54(3):142-9. doi: 10.2302/kjm.54.142.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common, life-threatening causes of acute respiratory failure that arise from a variety of local and systemic insults. The need for new specific therapies has led a number of investigators to examine the role of altered coagulation and fibrinolysis in the pathogenesis of ALI/ARDS. This review summarizes our current understanding of coagulation and fibrinolysis in human ALI/ARDS with an emphasis on pathways that could be potential therapeutic targets including the tissue factor pathway, the protein C pathway and modulation of fibrinolysis via plasminogen activator inhibitor-1. The available data suggest that clinical ALI and ARDS are characterized by profound alterations in both systemic and intra-alveolar coagulation and fibrinolysis. Fibrin deposition in the airspaces and lung microvasculature likely results from both activation of the coagulation cascade and impaired fibrinolysis, triggered by inflammation. Modulation of fibrin deposition in the lung through targeting activation and modulation of coagulation as well as fibrinolysis may be an important therapeutic target in clinical ALI/ARDS that deserves further exploration.
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是常见的、危及生命的急性呼吸衰竭病因，由多种局部和全身损伤引发。对新型特异性疗法的需求促使众多研究者探究凝血和纤溶改变在ALI/ARDS发病机制中的作用。本综述总结了我们目前对人类ALI/ARDS中凝血和纤溶的理解，重点关注可能成为潜在治疗靶点的途径，包括组织因子途径、蛋白C途径以及通过纤溶酶原激活物抑制剂-1对纤溶的调节。现有数据表明，临床ALI和ARDS的特征是全身和肺泡内凝血及纤溶均发生深刻改变。气腔和肺微血管中的纤维蛋白沉积可能是由炎症触发的凝血级联激活和纤溶受损共同导致的。通过靶向凝血和纤溶的激活及调节来调控肺内纤维蛋白沉积，可能是临床ALI/ARDS中一个重要的治疗靶点，值得进一步探索。
