title: Pulmonary tuberculosis induces a systemic hypercoagulable state.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands. Electronic address: l.m.kager@amc.uva.nl.
authors.forename: Liesbeth M
authors.initials: LM
authors.lastname: Kager
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Blok
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Medical Microbiology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ivar O
authors.initials: IO
authors.lastname: Lede
authors.affiliation: Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Wahid
authors.initials: W
authors.lastname: Rahman
authors.affiliation: Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Rumana
authors.initials: R
authors.lastname: Afroz
authors.affiliation: Department of Pulmonology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Pulmonology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Bresser
authors.affiliation: Department of Pulmonology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Pulmonology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Jaring S
authors.initials: JS
authors.lastname: van der Zee
authors.affiliation: Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Ghose
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Medical Microbiology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Visser
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Medical Microbiology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Menno D
authors.initials: MD
authors.lastname: de Jong
authors.affiliation: Department Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Tanck
authors.affiliation: Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Abu Shahed M
authors.initials: AS
authors.lastname: Zahed
authors.affiliation: Department of Microbiology, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Khan Mashrequl
authors.initials: KM
authors.lastname: Alam
authors.affiliation: Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Mahtabuddin
authors.initials: M
authors.lastname: Hassan
authors.affiliation: Chest Disease Clinic Chittagong (CDCC), Chittagong, Bangladesh.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hossain
authors.affiliation: Department of Pulmonology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Cornelis Van't
authors.initials: CV
authors.lastname: Veer
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, UK.
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Vascular Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Division of Infectious Diseases, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000990:Antithrombin III; D001459:Bangladesh; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D011446:Prospective Studies; D019851:Thrombophilia / Q000209:etiology*; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000150:complications*
chemical_list: D015415:Biomarkers; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases
keywords: Bronchoscopy; Coagulation; Fibrinolysis; Lung inflammation; Tuberculosis