Coagulation abnormalities in acute lung injury and sepsis
Coagulation abnormalities in acute lung injury and sepsis
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DOI：
10.1165/ajrcmb.22.4.f184
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发表时间：
2000-04-01
影响因子：
6.4
通讯作者：
Abraham, E
中科院分区：
文献类型：
--
作者：
Abraham, E
肺泡内和血管内纤维蛋白沉积常见于急性肺损伤 (ALI) 或急性呼吸窘迫综合征 (ARDS)(1, 2)。纤维蛋白沉积物通过增加血管通透性、激活内皮细胞产生促炎细胞因子和其他介质、诱导活化中性粒细胞的积累以及调节肺部的免疫调节反应来增强炎症反应。内毒素的输注会在肺和其他器官中产生纤维蛋白沉积，这些广泛的血管内改变被认为会导致脓毒症中的多器官功能障碍 (3,4,5)。 Fan 及其同事现在表明，失血性休克可以增强小剂量内毒素的作用，在肺部形成促凝血环境，其中肺泡巨噬细胞产生的活性氧中间体 (ROI) 和肿瘤坏死因子-α (TNF-α) 发挥重要作用 (6)。 ARDS 患者肺部的促凝血活性增强 (7, 8)。组织因子（外源性凝血途径中的关键介质）水平在 ARDS 支气管肺泡灌洗 (BAL) 标本中升高，并且组织因子似乎在 ARDS 相关促凝血状态中发挥重要作用 (9, 10)。此外，纤维蛋白溶解过程在 ALI 中受到抑制，如 BAL 中纤溶酶原激活剂抑制剂 1 (PAI-1) 浓度增加所示，并且还可能有助于 ALI 中纤维蛋白的生成 (11)。在内毒素血症的实验模型中，抗凝组织纤溶酶原激活剂早期增加，随后 PAI-1 持续升高，导致抗纤溶状态延长 (12)。
Intraalveolar and intravascular fibrin deposition is frequently found in the setting of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)(1, 2). Fibrin deposits enhance inflammatory response by increasing vascular permeability, activating endothelial cells to produce proinflammatory cytokines and other mediators, inducing the accumulation of activated neutrophils, and modulating immunoregulatory responses in the lung. Infusions of endotoxin produce fibrin deposits in the lung and other organs, and these widespread intravascular alterations are postulated to contribute to multiple organ dysfunction in sepsis (3, 4, 5). Fan and colleagues now show that hemorrhagic shock can potentiate the effects of small doses of endotoxin, creating a procoagulant milieu in the lungs, in which reactive oxygen intermediates (ROI) and tumor necrosis factor-α (TNF-α) produced by alveolar macrophages have important roles (6). Procoagulant activity is enhanced in the lungs of patients with ARDS (7, 8). Levels of tissue factor, a pivotal mediator in the extrinsic coagulation pathway, are increased in ARDS bronchoalveolar lavage (BAL) specimens, and tissue factor appears to occupy an important role in the ARDS-associated procoagulant state (9, 10). In addition, fibrinolytic processes are inhibited in ALI, as shown by increased BAL concentrations of plasminogen activator inhibitor 1 (PAI-1), and may also contribute to fibrin generation in ALI (11). In experimental models of endotoxemia, early increases in the anticoagulant tissue plasminogen activator are rapidly followed by sustained elevations in PAI-1, leading to a prolonged antifibrinolytic state (12).