Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.

SummaryBronchoalveolar lavage fluids (BALF) from patients with hyper- sensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the 125I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-Inhibitor I (PAI-1) and α2-antiplasmin (α2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activi- ties between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and anti- fibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. α2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of enhanced procoagulant and sustained overall fibrinolytic activity, lavage D-dimer levels were elevated by more than one order of magnitude in all ILD patients. We conclude that the predominant alteration in alveolar hemostatic balance in all groups of ILD patients is an enhancement in TF factor pathway activity. Concomitantly, various compounds of the (anti-)fibrinolytic pathways present with altered concentrations, but the overall BALF fibrinolytic activity is largely unchanged. The net enhancement of fibrin turnover is significantly correlated with the decrease in lung compliance. Abbreviations: α2-AP – α2-antiplasmin; ARDS – acute respiratory distress syndrome; BAL – bronchoalveolar lavage; BALF – BAL fluids; BSA – bovine serum albumin; FEV1 – forced expired volume within 1 s; FP-A – fibrinopeptide A; FVC – forced vital capacity; ILD – interstitial lung disease; IPF – idiopathic pulmonary fibrosis; HP – hypersensitivity pneumonitis; PAI-1 – plasminogen-activator-inhibitor-1; PBS – phosphate buffered saline; PCA – procoagulant activity; PL – phospholipid; PPQ – phospholipid-proteinquotient; SARC – sarcoidosis; t-PA – tissue-type plasminogen activator; u-PA – urokinase-type plasminogen activator