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Original article
Presence of a prothrombotic state in people with idiopathic pulmonary fibrosis: a population-based case–control study
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  1. Vidya Navaratnam1,2,
  2. Andrew W Fogarty1,
  3. Tricia McKeever1,
  4. Norma Thompson2,
  5. Gisli Jenkins2,
  6. Simon R Johnson3,
  7. Gerard Dolan4,
  8. Maruti Kumaran5,
  9. Kate Pointon5,
  10. Richard B Hubbard1
  1. 1Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
  2. 2Nottingham Respiratory Research Unit, Nottingham City Hospital, Nottingham, UK
  3. 3Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, UK
  4. 4Department of Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK
  5. 5Department of Radiology, Nottingham University Hospitals NHS Trust, Nottingham, UK
  1. Correspondence to Dr Vidya Navaratnam, Nottingham Respiratory Research Unit, Clinical Sciences Building, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK; vidya.navaratnam{at}nottingham.ac.uk

Abstract

Background Laboratory studies suggest that the clotting cascade is activated in fibrotic lungs. Since humans vary in their tendency to clot due to a variety of inherited or acquired defects, we investigated whether a prothrombotic state increases the chance of developing idiopathic pulmonary fibrosis (IPF) and/or worsens the prognosis of IPF.

Methods We recruited 211 incident cases of IPF and 256 age- and sex-matched general population controls and collected data on medical history, medication, smoking habit, blood samples as well as lung function and high-resolution CT scans done as part of routine clinical care. A prothrombotic state was defined as the presence of at least one inherited or acquired clotting defect or marker of fibrinolytic dysfunction. We used logistic regression to quantify the association between a prothrombotic state and IPF adjusted for age, sex, smoking habit and highly sensitive C reactive protein. Cox regression was used to determine the influence of a prothrombotic state on survival.

Results Cases were more than four times more likely than controls to have a prothrombotic state (OR 4.78, 95% CI 2.93 to 7.80; p<0.0001). Cases with a prothrombotic state were also likely to have more severe disease (forced vital capacity <70% predicted) at presentation (OR 10.79, 95% CI 2.43 to 47.91) and had a threefold increased risk of death (HR 3.26, 95% CI 1.09 to 9.75).

Conclusions People with IPF are more likely to have a prothrombotic state than general population controls and the presence of a prothrombotic state has an adverse impact on survival.

  • Idiopathic pulmonary fibrosis
  • Interstitial Fibrosis
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