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Pulmonary tuberculosis induces a systemic hypercoagulable state - 01/03/15

Doi : 10.1016/j.jinf.2014.10.006 
Liesbeth M. Kager a, b, , Dana C. Blok a, b, Ivar O. Lede a, d, Wahid Rahman k, Rumana Afroz k, Paul Bresser e, j, Jaring S. van der Zee e, j, Aniruddha Ghose k, Caroline E. Visser a, d, Menno D. de Jong a, d, Michael W. Tanck f, Abu Shahed M. Zahed k, Khan Mashrequl Alam l, Mahtabuddin Hassan k, Ahmed Hossain m, p, Rene Lutter e, i, Cornelis van't Veer a, b, Arjen M. Dondorp n, o, Joost C.M. Meijers g, h, Tom van der Poll a, b, c
a Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands 
b Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands 
c Division of Infectious Diseases, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands 
d Department of Medical Microbiology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands 
e Department of Pulmonology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands 
f Department Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands 
g Department of Experimental Vascular Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands 
h Department of Vascular Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands 
i Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands 
j Department of Pulmonology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands 
k Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh 
l Department of Microbiology, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh 
m Chest Disease Clinic Chittagong (CDCC), Chittagong, Bangladesh 
n Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand 
o Centre for Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, UK 

Corresponding author. Center for Experimental and Molecular Medicine (CEMM)/Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. Tel.: +31 20 566 5910; fax: +31 20 697 7192.

Summary

Objectives

Human tuberculosis (TB) remains an important cause of death globally. Bangladesh is one of the most affected countries. We aimed to investigate the impact of pulmonary TB on pro- and anticoagulant mechanisms.

Methods

This prospective study was conducted in Chittagong, Bangladesh. We performed an in-depth analysis of coagulation activation and inhibition in plasma obtained from 64 patients with primary lung TB and 11 patients with recurrent lung TB and compared these with 37 healthy controls. Additionally, in nine patients coagulation activation was studied in bronchoalveolar lavage fluid (BALF) harvested from the site of infection and compared with BALF from a contralateral unaffected lung subsegment.

Results

Relative to uninfected controls, primary and recurrent TB were associated with a systemic net procoagulant state, as indicated by enhanced activation of coagulation (elevated plasma levels of thrombin-antithrombin complexes, D-dimer and fibrinogen) together with impaired anticoagulant mechanisms (reduced plasma levels of antithrombin, protein C activity, free protein S, and protein C inhibitor). Activation of coagulation did not correlate with plasma concentrations of established TB biomarkers. Coagulation activation could not be detected at the primary site of infection in a subset of TB patients.

Conclusions

Pulmonary TB is associated with a systemic hypercoagulable state.

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Highlights

Tuberculosis is one of the most common infectious diseases world-wide.
Besides pro-inflammatory responses, severe infections also involve haemostatic mechanisms.
During infection procoagulant factors are activated while anticoagulant mechanisms are suppressed.
Data on activation of the coagulation system during tuberculosis are highly limited.
We analyzed systemic coagulation and anticoagulant pathways in lung tuberculosis patients.
We show that pulmonary tuberculosis is associated with a systemic hypercoagulable state.

Le texte complet de cet article est disponible en PDF.

Keywords : Tuberculosis, Coagulation, Fibrinolysis, Lung inflammation, Bronchoscopy


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© 2014  The British Infection Association. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 70 - N° 4

P. 324-334 - avril 2015 Retour au numéro
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