Liesbeth M Kager1, Dana C Blok2, Ivar O Lede3, Wahid Rahman4, Rumana Afroz4, Paul Bresser5, Jaring S van der Zee5, Aniruddha Ghose4, Caroline E Visser3, Menno D de Jong3, Michael W Tanck6, Abu Shahed M Zahed4, Khan Mashrequl Alam7, Mahtabuddin Hassan4, Ahmed Hossain8, Rene Lutter9, Cornelis Van't Veer2, Arjen M Dondorp10, Joost C M Meijers11, Tom van der Poll12. 1. 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. 2. 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. 3. 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. 4. Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh. 5. Department of Pulmonology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Pulmonology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. 6. Department Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands. 7. Department of Microbiology, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh. 8. Chest Disease Clinic Chittagong (CDCC), Chittagong, Bangladesh. 9. 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. 10. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, UK. 11. 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. 12. 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.
Abstract
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.
OBJECTIVES:Humantuberculosis (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: Thao K T Nguyen; John d'Aigle; Luis Chinea; Zainab Niaz; Robert L Hunter; Shen-An Hwang; Jeffrey K Actor Journal: Am J Pathol Date: 2019-11-14 Impact factor: 4.307
Authors: Saskia Janssen; Charlotte Schutz; Amy M Ward; Mischa A M Huson; Robert J Wilkinson; Rosie Burton; Gary Maartens; Katalin A Wilkinson; Joost C M Meijers; René Lutter; Martin P Grobusch; Graeme Meintjes; Tom van der Poll Journal: J Infect Dis Date: 2017-01-15 Impact factor: 5.226