Summary
Bronchoalveolar 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
Keywords
Tissue factor - PAI-1 - u-PA - t-PA - interstitial lung disease (ILD)
