Procoagulant and plasminogen activator activities of bronchoalveolar fluid in patients with pulmonary sarcoidosis.

Tissue fibrin deposition may be an important component of inflammatory reactions. Current evidence suggests that intraalveolar procoagulant (PC) and plasminogen activator (PA) activities may be important determinants of local fibrin turnover in lung injury. In this study, we measured the PC and PA activities in cell-free bronchoalveolar lavage fluid (BALF) obtained from 17 patients with pulmonary sarcoidosis and 12 normal volunteers. Procoagulant activity was assayed by timing clot formation in a one-stage coagulation assay, and plasminogen activator activity was determined by measuring plasminogen-dependent lysis of [125I]fibrin. Mean PC activity in the sarcoidosis group was significantly elevated (102 +/- 25 versus 31.5 +/- 8.1 tissue thromboplastin units/ml; p less than 0.002), with 6 of 17 patient values beyond the 95% confidence limits of normals. These differences were not seen when PC activity was corrected for total protein in BAL. In contrast, PA activity tended to be lower in the sarcoidosis group (0.54 +/- 0.094 versus 0.643 +/- 0.106 Plough units/ml, p less than 0.3), and this difference became significant when PA was normalized to total protein (p less than 0.001). The ratio of procoagulant activity compared to plasminogen activator (PC/PA) was greater in the patients with sarcoidosis than normals (258 +/- 54 versus 40.3 +/- 6.4; p less than 0.001). The PC/PA ratios in 14 of 17 patients exceeded the 95% confidence limits of normals. In the sarcoidosis group, the PC/PA ratio correlated weakly with the number and percentage of lymphocytes retrieved by BAL. The plasminogen activator was a urokinase by molecular weight (53 kDa) and by comparing neutralization of PA activity by antibodies against urokinase and tissue plasminogen activator. The procoagulant was particulate and functioned as a factor X activator comprised of tissue thromboplastin and factor VII. We conclude that in pulmonary sarcoidosis, abnormal expression of procoagulant and plasminogen activator activities in alveolar fluid may favor accumulation of fibrin matrix at inflammatory foci.