Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome

Abstract

To cite this article: Glas GJ, van der Sluijs KF, Schultz MJ, Hofstra J-JH, van der Poll T, Levi M. Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome. J Thromb Haemost 2013; 11: 17-25.Summary. Enhanced intrapulmonary fibrin deposition as a result of abnormal broncho-alveolar fibrin turnover is a hallmark of acute respiratory distress syndrome (ARDS), pneumonia and ventilator-induced lung injury (VILI), and is important to the pathogenesis of these conditions. The mechanisms that contribute to alveolar coagulopathy are localized tissue factor-mediated thrombin generation, impaired activity of natural coagulation inhibitors and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. There is an intense and bidirectional interaction between coagulation and inflammatory pathways in the bronchoalveolar compartment. Systemic or local administration of anticoagulant agents (including activated protein C, antithrombin and heparin) and profibrinolytic agents (such as plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti-inflammatory effects of these therapies in ARDS and pneumonia.

Postexposure aerosolized heparin reduces lung injury in chlorine-exposed mice

“…Herein we expand this knowledge by reporting that mice exposed to 400 ppm of Cl 2 gas for 30 min and returned to room air also develop acute systemic hypocoagulation and pulmonary hypercoagulation at the same time, similar to that reported in patients with severe trauma (8) and smoke inhalation (17). Specifically, we show that mice exposed to Cl 2 and returned to room air exhibit activation of coagulation in the distal lung spaces, as indicated by the appearance of TAT complexes in the BALF, as well as in secondary activation of fibrinolysis in the plasma by formation of D-dimers.…”

“…Heparin may abate these processes by preventing the continued formation of thrombin or by acting as an anti-inflammatory, which prevents epithelial damage and exposure of pulmonary thrombin to the systemic coagulation system. Recent studies reported enhanced activation of the coagulation in the lungs of mice that developed ALI due to sulfur mustard inhalation (39) and smoke inhalation (17), which may account for airway obstruction by fibrin clots. However, these authors did not report the occurrence of systemic hypocoagulation in mice exposed to nitrogen mustard.…”

“…Previous studies have documented that inflammatory mediators activate the coagulation cascade, which plays an important role in the pathogenesis of ALI/ARDS (17,23,24). This association has been investigated in animal models with a number of different causes of lung injury, such as endotoxin, hyperoxia, trauma, hemorrhage, or pneumonia (2,7,8,14,44,54), but not in Cl 2 -induced lung injury.…”

Proteolytic Regulation of Epithelial Sodium Channels by Urokinase Plasminogen Activator

“…The balance between plasminogen activators and their corresponding inhibitors is disrupted in edematous lungs and pleural injuries, including acute lung injury, acute respiratory distress syndrome, high altitude pulmonary edema, and pleural effusions (1,9,10). Accumulating evidence from clinical studies and animal models has confirmed a depression in plasminogen activation in bronchoalveolar lavage or pleural fluid (11)(12)(13).…”

Coagulation profile in patients with H1N1 influenza A infection undergoing treatment for haematological malignancies

“…Mechanisms of coagulopathy in pneumonia and ARDS are important to the pathogenesis of these processes [4].…”