Coagulation abnormalities in acute lung injury and sepsis.

Abstract

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 factora (TNFa ) 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).