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Pulmonary fibrosis as a risk factor for thromboembolic disease



Chronic obstructive pulmonary disease (COPD) and lung cancer are well known to be associated with increased risk for venous thromboembolism (VTE). However, there are few data about the association between idiopathic pulmonary fibrosis (IPF) and VTE.

Aim of this study

The aim of the study was to investigate the prevalence of venous thromboembolic events in hospitalized IPF patients and compare it with the incidence in COPD patients.

Patients and methods

We retrospectively analyzed the database of interstitial lung disease from 2007 to 2013. We included 629 IPF patients after exclusion of patients with secondary pulmonary fibrosis and those with a concurrent diagnosis of COPD or lung cancer. VTE disease was defined as either deep venous thrombosis, pulmonary embolism, or both deep venous thrombosis and pulmonary embolism. For comparison, we also analyzed the database of COPD patients.


Out of the 629 included IPF patients, 13 had thromboembolic events, showing a prevalence for VTE in IPF that is significantly higher than that in COPD (2.1 vs. 1.1%; odds ratio: 1.9; confidence interval: 1.039–3.530; P = 0.035). The prevalence is also significantly higher in female and nonsmoker IPF patients compared with COPD patients (P = 0.008 and 0.011 respectively). Among IPF patients, men had significantly lower risk for VTE compared with women (P = 0.045).


IPF, especially in women, is associated with increased risk for VTE, being greater than the risk in COPD.


  1. Gunen H, Gulbas G, In E, Yetkin O, Hacievliyagil SS. Venous thromboemboli and exacerbations of COPD. Eur Respir J 2010; 35:1243–1248.

    Article  CAS  Google Scholar 

  2. Ahmet U, Mehmet K, Esra U, Selma Y, Funda C, Ercüment E. Prognostic significance of plasma D-dimer levels in patients with lung cancer. Eur J Gen Med 2010; 7:155–160.

    Google Scholar 

  3. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141(Suppl):7S–47S.

    Article  CAS  Google Scholar 

  4. Fihn SD, Gardin JM, Abrams J, Berra K. American College of Cardiology Foundation/American Heart Association Task Force, et al. ACCF/ AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012; 126:354–471.

    Google Scholar 

  5. Olman MA, Mackman N, Gladson CL, Moser KM, Loskutoff DJ. Changes in procoagulant and fibrinolytic gene expression during bleomycin-induced lung injury in the mouse. J Clin Invest 1995; 96:1621–1630.

    Article  CAS  Google Scholar 

  6. Imokawa S, Sato A, Hayakawa H, Kotani M, Urano T, Takada A. Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis. Am J Respir Crit Care Med 1997; 156(Pt 1):631–636.

    Article  CAS  Google Scholar 

  7. Kobayashi H, Gabazza EC, Taguchi O, Wada H, Takeya H, Nishioka J, et al. Protein C anticoagulant system in patients with interstitial lung disease. Am J Respir Crit Care Med 1998; 157(Pt 1):1850–1854.

    Article  CAS  Google Scholar 

  8. Fujii M, Hayakawa H, Urano T, Sato A, Chida K, Nakamura H, Takada A. Relevance of tissue factor and tissue factor pathway inhibitor for hypercoagulable state in the lungs of patients with idiopathic pulmonary fibrosis. Thromb Res 2000; 99:111–117.

    Article  CAS  Google Scholar 

  9. Gunther A, Mosavi P, Ruppert C, Heinemann S, Temmesfeld B, Velcovsky HG, et al. Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease. Thromb Haemost 2000; 83:853–860.

    Article  CAS  Google Scholar 

  10. Kubo H, Nakayama K, Yanai M, Suzuki T, Yamaya M, Watanabe M, Sasaki H. Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 2005; 128:1475–1482.

    Article  CAS  Google Scholar 

  11. Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW. The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med 2008; 178:1257–1261.

    Article  Google Scholar 

  12. Sprunger DB, Olson AL, Huie TJ, Fernandez-Perez ER, Fischer A, Solomon JJ, et al. Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease. Eur Respir J 2012; 39:125–132.

    Article  CAS  Google Scholar 

  13. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. ATS/ ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183:788–824.

    Article  Google Scholar 

  14. Sode BF, Dahl M, Nielsen SF, Nordestgaard BG. Venous thromboembolism and risk of idiopathic interstitial pneumonia: a nationwide study. Am J Respir Crit Care Med 2010; 181:1085–1092.

    Article  Google Scholar 

  15. Nathan SD, Barnett SD, Urban BA, Nowalk C, Moran BR, Burton N. Pulmonary embolism in idiopathic pulmonary fibrosis transplant recipients. Chest 2003; 123:1758–1763.

    Article  Google Scholar 

  16. Garcia-Salcedo JA, de la TorreMM, Delgado M, Paradela M, Fieira EM, Gonzalez D, et al. Complications during clinical evolution in lung transplantation: pulmonary embolism. Transplant Proc 2010; 42:3220–3221.

    Article  CAS  Google Scholar 

  17. Stein, PD, Beemath, A, Meyers FA, Olson RE. Pulmonary embolism and deep venous thrombosis in hospitalized adults with chronic obstructive pulmonary disease. J Cardiovasc Med (Hagerstown) 2007; 8:253–257.

    Article  Google Scholar 

  18. Chen WJ, Lin CC, Lin CY, Chang YJ, Sung FC, Kao CH, Yeh JJ. Pulmonary embolism in chronic obstructive pulmonary disease: a population-based cohort study. COPD 2014; 11:438–443.

    Article  Google Scholar 

  19. Mispelaere D, Glerant JC, Audebert M, Remond A, Sevestre-Pietri MA, Jounieaux V. Pulmonary embolism and sibilant types of chronic obstructive pulmonary disease decompensations. Rev Mal Respir 2002; 19:415–423.

    CAS  PubMed  Google Scholar 

  20. Tillie-Leblond I, Marquette CH, Perez T, Scherpereel A, Zanetti C, Tonnel AB, Remy-Jardin M. Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors. Ann Intern Med 2006; 144:390–396.

    Article  Google Scholar 

  21. Holst AG, Jensen G, Prescott E. Risk factors for venous thromboembolism: results from the Copenhagen City Heart Study. Circulation 2010; 121:1896–1903.

    Article  Google Scholar 

  22. Yarnell JW, Sweetnam PM, Rumley A, Lowe GD. Lifestyle and hemostatic risk factors for ischemic heart disease: the Caerphilly Study. Arterioscler Thromb Vasc Biol 2000; 20:271–279.

    Article  CAS  Google Scholar 

  23. Lee KW, Lip GY. Effects of lifestyle on hemostasis, fibrinolysis, and platelet reactivity: a systematic review. Arch Intern Med 2003; 163:2368–2392.

    Article  Google Scholar 

  24. Chambers RC. Procoagulant signaling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention? Br J Pharmacol 2008; 153:367–378.

    Article  Google Scholar 

  25. Collard HR, Calfee CS, Wolters PJ, Song JW, Hong SB, Brady S, et al. Plasma biomarker profiles in acute exacerbation of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2010; 299:3–7.

    Article  Google Scholar 

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Correspondence to Shereen Farghaly MD.

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Farghaly, S., El-Abdin, A.Z. Pulmonary fibrosis as a risk factor for thromboembolic disease. Egypt J Bronchol 9, 160–164 (2015).

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