Local abnormalities of coagulation and fibrinolytic pathways that promote alveolar fibrin deposition in the lungs of baboons with diffuse alveolar damage

• Published in: The Journal of clinical investigation Vol. 84; no. 1; pp. 181 - 193
• Main Authors: IDELL, S, PETERS, J, JAMES, K. K, FAIR, D. S, COALSON, J. J
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01-07-1989
• Subjects: alpha-2-Antiplasmin - metabolism; Animals; Biological and medical sciences; Blood Coagulation; Bronchoalveolar Lavage Fluid - metabolism; Electrophoresis, Polyacrylamide Gel; Factor X - metabolism; Fibrin - metabolism; Fibrinolysis; Humans; Hydrolysis; Medical sciences; Papio; Plasminogen - analysis; Plasminogen - immunology; Plasminogen Activators - metabolism; Pneumology; Proteins - metabolism; Pulmonary Alveoli - metabolism; Pulmonary Alveoli - pathology; Radioimmunoassay; Respiratory system : syndromes and miscellaneous diseases; Blood coagulation; Respiratory disease; Acute; Etiopathogenesis; Monkey; Respiratory intensive care; Fibrin; Vertebrata; Experimental disease; Mammalia; Respiratory failure; Pulmonary alveolus; Primates; Deposition
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI114139

Because alveolar fibrin is a prominent histologic feature of diffuse lung injury in baboons, we hypothesized that local abnormalities of pathways of fibrin turnover would favor fibrin deposition in the alveolar space. To test this hypothesis, procoagulant and fibrinolytic activities were characterized in serial bronchoalveolar lavage (BAL) of baboons with evolving diffuse alveolar damage (DAD) induced by exposure to 100% O2. BAL procoagulant activity, characterized mainly as the tissue factor-Factor VII complex, was markedly increased after induction of DAD. Extrinsic pathway inhibitor was likewise increased in BAL during evolving DAD but was insufficient to control coagulation. Urokinase-like fibrinolytic activity was usually detectable in baseline BAL but was undetectable after 7 d of O2. DAD BAL contained significantly increased plasminogen levels, plasmin inhibitor activity sufficient to neutralize all plasmin produced by BAL plasminogen activator found in control BAL and detectable plasminogen activator inhibitor-1. Antiplasmin activity was due, in part, to increased alpha 2-antiplasmin. These changes correlated with quantitatively increased alveolar fibrin deposition demonstrated by histologic and morphometric analyses. Multiple abnormalities of pathways of fibrin turnover occur concurrently in the alveolar compartment of the lungs of baboons with DAD, which collectively predispose to diffuse alveolar fibrin deposition.