title: Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor.
abstract: BACKGROUND
  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 age-matched 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 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±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.
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Cottingham, United Kingdom.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Crooks
authors.affiliation: Respiratory Medicine, New Cross Hospital, Wolverhampton, United Kingdom.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Fahim
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Cottingham, United Kingdom.
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Naseem
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Cottingham, United Kingdom.
authors.forename: Alyn H
authors.initials: AH
authors.lastname: Morice
authors.affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Cottingham, United Kingdom.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hart
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D010973:Platelet Adhesiveness
chemical_list: D019007:P-Selectin; D005340:Fibrinogen