Microparticles-associated tissue factor activity is increased in bronchoalveolar lavage of patients with pulmonary fibrosis and correlates with functional impairment

Background: The activation of the coagulation cascade plays a role in the pathogenesis of fibrotic lung diseases. Furthermore, anticoagulants are effective in experimental lung fibrosis and possibly in patients with idiopathic pulmonary fibrosis. Microparticles (MP) are cell derived procoagulant and proinflammatory vesicles that can express tissue factor (TF); MP represent a storage pool of bioactive effectors and are emerging as a new family of physiologically relevant mediators. Aim: To evaluate the presence of TF-bearing MP in the bronchoalveolar lavage fluid (BALF) of patients with pulmonary fibrosis (PF) in comparison with control patients, and to correlate their concentration with the degree of functional impairment. Methods: Seven patients with PF and 10 control patients with suspected lung cancer or infectious diseases underwent bronchoscopy. The presence of MP was evaluated through a prothrombinase assay that measures phosphatidylserine (PS) concentration; TF activity was assessed by a one-stage clotting assay. Results: The BALF of patients with PF had a higher concentration of microparticles (87.23 [67.21-108.8] vs 49.19 [29.50-77.22] nM PS, p=.05) and a greater TF activity (27144 [17253-29998] vs 8596 [4019-21962] arbitrary U, p=.05) (data expressed as median [interquartile range]). We found a significant negative correlation between MP-associated TF activity and forced vital capacity% predicted (r 2 =.95, p 2 =.56, p=.05). Conclusions: Our preliminary data are consistent with an involvement of TF-bearing procoagulant MP in the pathogenesis of PF and in disease progression.