Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor

Abstract

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to agematched controls. Methods: Whole blood flow cytometry was used to measure platelet-monocyte aggregate formation, platelet P-selectin expression and platelet fibrinogen binding at basal levels and following stimulation with platelet agonists. A plasma swap approach was used to assess the effect of IPF plasma on control platelets. Results: Subjects with IPF showed greater platelet reactivity than controls. Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 mM ADP (1.9% positive plusmn;0.5 (mean plusmn;SEM) versus 0.7%plusmn;0.1; p =0.03), 1 μM ADP (9.8%plusmn;1.3 versus 3.3%plusmn;0.8; p<0.01) and 10 μM ADP (41.3%plusmn;4.2 versus 22.5%plusmn;2.6; p< 0.01). Platelet fibrinogen binding was also increased, and platelet activation resulted in increased platelet-monocyte aggregate formation in IPF patients. Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma. Conclusions: IPF patients exhibit increased platelet reactivity compared with controls. This hyperactivity may result from the plasma environment since control platelets exhibit increased activation when exposed to IPF plasma.