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Published in: Journal of Thrombosis and Thrombolysis 1/2022

01-01-2022 | Idiopathic Pulmonary Fibrosis

Risk of recurrent venous thromboembolism and bleeding in patients with interstitial lung disease: a cohort study

Authors: Raphael Le Mao, Thomas Ropars, Cécile Tromeur, Aude Barnier, Baptiste Hourmant, Marie Guegan, David Jimenez, Christophe Leroyer, Karine Lacut, Francis Couturaud

Published in: Journal of Thrombosis and Thrombolysis | Issue 1/2022

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Abstract

Interstitial lung disease (ILD) encompasses various parenchymal lung disorders, which has the potential to increase the risk of venous thromboembolism (VTE). To evaluate, in patients with ILD and VTE, the risk of recurrent VTE during follow-up after stopping anticoagulation. This was a cohort of patients with a first VTE recruited between 1997 and 2015. The primary outcome was adjudicated fatal or nonfatal recurrent VTE after stopping anticoagulation. Main secondary outcomes were major or clinically relevant non-major bleeding under anticoagulation. Among 4314 patients with VTE, 50 had ILD diagnosed before VTE. Of these, anticoagulation was stopped in 30 patients after a median duration of 180 days and continued indefinitely in 20 patients. During a median follow-up of 27.8 months after anticoagulation discontinuation, recurrent VTE occurred in 15 on 30 patients (annual incidence of 19.2 events per 100-person-years [95%CI 12.0–29.3], case-fatality rate of 6.7% [95%CI 1.21–29.8]). The risk of recurrence was threefold higher when VTE was unprovoked and case-fatality rate of recurrence was increased by 3 when VTE index was PE. During the anticoagulant period, (median duration of 8.6 months), 6 patients had a major or clinically relevant bleeding (annual incidence of 7.3 events per 100-person-years [95%CI 3.4–15.1], case-fatality rate of 16.7% [95%CI 3.0–56.4]). In patients with ILD, the risk of recurrent VTE after stopping anticoagulation and the risk of bleeding under anticoagulation were very high. Our results suggest that anticoagulation should not be prolonged beyond 3–6 months of anticoagulation in most of cases.
Literature
1.
go back to reference Heit JA, Mohr DN, Silverstein MD, Petterson TM, O’Fallon WM, Melton LJ (2000) Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 160(6):761–768CrossRef Heit JA, Mohr DN, Silverstein MD, Petterson TM, O’Fallon WM, Melton LJ (2000) Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 160(6):761–768CrossRef
2.
go back to reference Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R et al (2007) The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 92(2):199–205CrossRef Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R et al (2007) The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 92(2):199–205CrossRef
3.
go back to reference Carrier M, Le Gal G, Wells PS, Rodger MA (2010) Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 152(9):578–589CrossRef Carrier M, Le Gal G, Wells PS, Rodger MA (2010) Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 152(9):578–589CrossRef
4.
go back to reference Sode BF, Dahl M, Nielsen SF, Nordestgaard BG (2010) Venous thromboembolism and risk of idiopathic interstitial pneumonia: a nationwide study. Am J Respir Crit Care Med 181(10):1085–1092CrossRef Sode BF, Dahl M, Nielsen SF, Nordestgaard BG (2010) Venous thromboembolism and risk of idiopathic interstitial pneumonia: a nationwide study. Am J Respir Crit Care Med 181(10):1085–1092CrossRef
5.
go back to reference Travis WD, Costabel U, Hansell DM, King TE, Lynch DA, Nicholson AG et al (2013) An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 188(6):733–748CrossRef Travis WD, Costabel U, Hansell DM, King TE, Lynch DA, Nicholson AG et al (2013) An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 188(6):733–748CrossRef
6.
go back to reference Kotani I, Sato A, Hayakawa H, Urano T, Takada Y, Takada A (1995) Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis. Thromb Res 77(6):493–504CrossRef Kotani I, Sato A, Hayakawa H, Urano T, Takada Y, Takada A (1995) Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis. Thromb Res 77(6):493–504CrossRef
7.
go back to reference Navaratnam V, Fogarty AW, McKeever T, Thompson N, Jenkins G, Johnson SR et al (2014) Presence of a prothrombotic state in people with idiopathic pulmonary fibrosis: a population-based case-control study. Thorax 69(3):207–215CrossRef Navaratnam V, Fogarty AW, McKeever T, Thompson N, Jenkins G, Johnson SR et al (2014) Presence of a prothrombotic state in people with idiopathic pulmonary fibrosis: a population-based case-control study. Thorax 69(3):207–215CrossRef
8.
go back to reference Wygrecka M, Kwapiszewska G, Jablonska E, von Gerlach S, Henneke I, Zakrzewicz D et al (2011) Role of protease-activated receptor-2 in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 183(12):1703–1714CrossRef Wygrecka M, Kwapiszewska G, Jablonska E, von Gerlach S, Henneke I, Zakrzewicz D et al (2011) Role of protease-activated receptor-2 in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 183(12):1703–1714CrossRef
9.
go back to reference Chambers RC (2008) Procoagulant signalling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention? Br J Pharmacol 153(Suppl 1):S367-378CrossRef Chambers RC (2008) Procoagulant signalling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention? Br J Pharmacol 153(Suppl 1):S367-378CrossRef
10.
go back to reference Scotton CJ, Krupiczojc MA, Königshoff M, Mercer PF, Lee YCG, Kaminski N et al (2009) Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. J Clin Invest 119(9):2550–2563PubMedPubMedCentral Scotton CJ, Krupiczojc MA, Königshoff M, Mercer PF, Lee YCG, Kaminski N et al (2009) Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. J Clin Invest 119(9):2550–2563PubMedPubMedCentral
11.
go back to reference Sprunger DB, Olson AL, Huie TJ, Fernandez-Perez ER, Fischer A, Solomon JJ et al (2012) Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease. Eur Respir J 39(1):125–132CrossRef Sprunger DB, Olson AL, Huie TJ, Fernandez-Perez ER, Fischer A, Solomon JJ et al (2012) Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease. Eur Respir J 39(1):125–132CrossRef
12.
go back to reference Dalleywater W, Powell HA, Fogarty AW, Hubbard RB, Navaratnam V (2014) Venous thromboembolism in people with idiopathic pulmonary fibrosis: a population-based study: Table 1–. Eur Respir J 44(6):1714–1715CrossRef Dalleywater W, Powell HA, Fogarty AW, Hubbard RB, Navaratnam V (2014) Venous thromboembolism in people with idiopathic pulmonary fibrosis: a population-based study: Table 1–. Eur Respir J 44(6):1714–1715CrossRef
13.
go back to reference Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW (2008) The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med 178(12):1257–1261CrossRef Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW (2008) The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med 178(12):1257–1261CrossRef
14.
go back to reference Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H et al (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 149(2):315–352CrossRef Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H et al (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 149(2):315–352CrossRef
15.
go back to reference Konstantinides S (2008) Clinical practice. Acute pulmonary embolism. N Engl J Med 359(26):2804–13CrossRef Konstantinides S (2008) Clinical practice. Acute pulmonary embolism. N Engl J Med 359(26):2804–13CrossRef
16.
go back to reference Kearon C, Julian JA, Newman TE, Ginsberg JS (1998) Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Practice Guidelines Initiative. Ann Intern Med 128(8):663–77CrossRef Kearon C, Julian JA, Newman TE, Ginsberg JS (1998) Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Practice Guidelines Initiative. Ann Intern Med 128(8):663–77CrossRef
17.
go back to reference PIOPED Investigators (1990) Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 263(20):2753–2759 PIOPED Investigators (1990) Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 263(20):2753–2759
18.
go back to reference Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W et al (2010) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost JTH 8(1):202–204CrossRef Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W et al (2010) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost JTH 8(1):202–204CrossRef
19.
go back to reference Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost JTH 3(4):692–694 Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost JTH 3(4):692–694
20.
go back to reference Hansson PO, Sörbo J, Eriksson H (2000) Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med 160(6):769–774CrossRef Hansson PO, Sörbo J, Eriksson H (2000) Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med 160(6):769–774CrossRef
21.
go back to reference Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M et al (1996) The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 125(1):1–7CrossRef Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M et al (1996) The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 125(1):1–7CrossRef
22.
go back to reference Couturaud F, Sanchez O, Pernod G, Mismetti P, Jego P, Duhamel E et al (2015) Six months vs extended oral anticoagulation after a first episode of pulmonary embolism: the PADIS-PE Randomized Clinical Trial. JAMA 314(1):31–40CrossRef Couturaud F, Sanchez O, Pernod G, Mismetti P, Jego P, Duhamel E et al (2015) Six months vs extended oral anticoagulation after a first episode of pulmonary embolism: the PADIS-PE Randomized Clinical Trial. JAMA 314(1):31–40CrossRef
23.
go back to reference Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA et al (2003) Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 349(7):631–639CrossRef Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA et al (2003) Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 349(7):631–639CrossRef
24.
go back to reference Boutitie F, Pinede L, Schulman S, Agnelli G, Raskob G, Julian J et al (2011) Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials. BMJ 342:d3036CrossRef Boutitie F, Pinede L, Schulman S, Agnelli G, Raskob G, Julian J et al (2011) Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials. BMJ 342:d3036CrossRef
25.
go back to reference Beyth RJ, Quinn LM, Landefeld CS (1998) Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 105(2):91–99CrossRef Beyth RJ, Quinn LM, Landefeld CS (1998) Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 105(2):91–99CrossRef
26.
go back to reference Beyth RJ, Quinn L, Landefeld CS (2000) A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin. A randomized, controlled trial. Ann Intern Med 133(9):687–95CrossRef Beyth RJ, Quinn L, Landefeld CS (2000) A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin. A randomized, controlled trial. Ann Intern Med 133(9):687–95CrossRef
27.
go back to reference Kubo H, Nakayama K, Yanai M, Suzuki T, Yamaya M, Watanabe M et al (2005) Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 128(3):1475–1482CrossRef Kubo H, Nakayama K, Yanai M, Suzuki T, Yamaya M, Watanabe M et al (2005) Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 128(3):1475–1482CrossRef
28.
go back to reference King TE, Pardo A, Selman M (2011) Idiopathic pulmonary fibrosis. Lancet Lond Engl 378(9807):1949–1961CrossRef King TE, Pardo A, Selman M (2011) Idiopathic pulmonary fibrosis. Lancet Lond Engl 378(9807):1949–1961CrossRef
29.
go back to reference Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D et al (2011) Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. The Lancet 377(9779):1760–1769CrossRef Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D et al (2011) Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. The Lancet 377(9779):1760–1769CrossRef
30.
go back to reference Noth I, Anstrom KJ, Calvert SB, de Andrade J, Flaherty KR, Glazer C et al (2012) A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 186(1):88–95CrossRef Noth I, Anstrom KJ, Calvert SB, de Andrade J, Flaherty KR, Glazer C et al (2012) A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 186(1):88–95CrossRef
31.
go back to reference Kreuter M, Wijsenbeek MS, Vasakova M, Spagnolo P, Kolb M, Costabel U et al (2016) Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis. Eur Respir J 47(6):1776–1784CrossRef Kreuter M, Wijsenbeek MS, Vasakova M, Spagnolo P, Kolb M, Costabel U et al (2016) Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis. Eur Respir J 47(6):1776–1784CrossRef
32.
go back to reference Behr J, Kreuter M, Hoeper MM, Wirtz H, Klotsche J, Koschel D et al (2015) Management of patients with idiopathic pulmonary fibrosis in clinical practice: the INSIGHTS-IPF registry. Eur Respir J 46(1):186–196CrossRef Behr J, Kreuter M, Hoeper MM, Wirtz H, Klotsche J, Koschel D et al (2015) Management of patients with idiopathic pulmonary fibrosis in clinical practice: the INSIGHTS-IPF registry. Eur Respir J 46(1):186–196CrossRef
33.
go back to reference Kraaijpoel N, Tritschler T, Guillo E, Girard P, Le Gal G (2019) Definitions, adjudication, and reporting of pulmonary embolism-related death in clinical studies: a systematic review. J Thromb Haemost 17(10):1590–1607CrossRef Kraaijpoel N, Tritschler T, Guillo E, Girard P, Le Gal G (2019) Definitions, adjudication, and reporting of pulmonary embolism-related death in clinical studies: a systematic review. J Thromb Haemost 17(10):1590–1607CrossRef
Metadata
Title
Risk of recurrent venous thromboembolism and bleeding in patients with interstitial lung disease: a cohort study
Authors
Raphael Le Mao
Thomas Ropars
Cécile Tromeur
Aude Barnier
Baptiste Hourmant
Marie Guegan
David Jimenez
Christophe Leroyer
Karine Lacut
Francis Couturaud
Publication date
01-01-2022
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 1/2022
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-021-02518-z

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