Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pn eumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sar coidosis (SARC, n = 48) were investigated for alterations in the alveolar h emostatic balance. Healthy individuals (n = 21) served as Controls. Procoag ulant activity (PCA), tissue factor (TF) activity and F VII activity were a ssessed by means of specific recalcification assays. The overall fibrinolyt ic activity (FA) was measured using the I-125-labeled fibrin plate assay. F ibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokina se (u-PA) or tissue type (t-PA), PA-Inhibitor I (PAI-1) and alpha(2)-antipl asmin (alpha(2)-AP) were determined by ELISA technique. As compared to Cont rols, 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 signi ficant difference in procoagulant activities between the different ILD enti ties, but the increase in TF was significantly correlated with deterioratio n of lung compliance. Overall fibrinolytic activity did not significantly d iffer between ILD entities and Controls, although some reduction in IPF sub jects was observed. Nevertheless, changes in the profile of the different p ro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels we re significantly reduced in all ILD groups. alpha(2)-AP was markedly elevat ed throughout, whereas PAI-1 levels were lowered. As a balance of enhanced procoagulant and sustained overall fibrinolytic activity, lavage D-dimer le vels 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 activ ity. Concomitantly, various compounds of the (anti-)fibrinolytic pathways p resent with altered concentrations, but the overall BALF fibrinolytic activ ity is largely unchanged. The net enhancement of fibrin turnover is signifi cantly correlated with the decrease in lung compliance.