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급성폐손상에 응고 및 섬유소 용해과정의 역할

The Role of the Coagulation and Fibrinolytic Pathway in Acute Lung Injury

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초록

Acute lung injury (ALI) is a common, life-threatening cause of acute respiratory failure, which is ultimately caused by a variety of local and systemic insults. Alterations in the coagulation and fibrinolysis profiles are present in almost all the patients suffering with ALI. The classic histologic findings in ALI patients include alveolar fibrin formation and microthrombi in the pulmonary vasculature. Decreased circulating levels of protein C and increased concentrations of thrombomodulin are present in patients with septic and nonseptic ALI. The circulating and pulmonary concentrations of plasminogen activator inhibitor-1 (PAI-1) are increased in the setting of ALI, and the degree of elevation in the PAI-1 level directly correlates with mortality. 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. This review summarizes the current understanding of coagulation and fibrinolysis in ALI with an emphasis on the pathways that could be potential therapeutic targets, including the tissue factor pathway, the protein C pathway and the modulation of fibrinolysis via plasminogen activator inhibitor-1.

Abstract

Acute lung injury (ALI) is a common, life-threatening cause of acute respiratory failure, which is ultimately caused by a variety of local and systemic insults. Alterations in the coagulation and fibrinolysis profiles are present in almost all the patients suffering with ALI. The classic histologic findings in ALI patients include alveolar fibrin formation and microthrombi in the pulmonary vasculature. Decreased circulating levels of protein C and increased concentrations of thrombomodulin are present in patients with septic and nonseptic ALI. The circulating and pulmonary concentrations of plasminogen activator inhibitor-1 (PAI-1) are increased in the setting of ALI, and the degree of elevation in the PAI-1 level directly correlates with mortality. 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. This review summarizes the current understanding of coagulation and fibrinolysis in ALI with an emphasis on the pathways that could be potential therapeutic targets, including the tissue factor pathway, the protein C pathway and the modulation of fibrinolysis via plasminogen activator inhibitor-1.

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