{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:25:37Z","timestamp":1789586737450,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Pulmonary tuberculosis (TB) is accompanied by inflammation-driven hypercoagulability and increased venous thromboembolism risk. We investigated whether the natural anticoagulants protein C and free protein S are reduced in active TB and whether baseline levels are associated with bacillary burden, treatment response, CT evolution, and pulmonary embolism (PE). Methods: We conducted a prospective cohort study in Romania, including 63 adults with newly diagnosed, bacteriologically confirmed, drug-susceptible pulmonary TB and 30 TB-free controls (October 2024\u2013December 2025). Venous blood was collected at baseline (before anti-TB therapy) and at 6 months to quantify inflammatory and coagulation parameters, protein C, and free protein S. Sputum AFB smear was assessed at baseline, 2 months, and 6 months; chest CT was performed at baseline and 6 months. Propensity score matching (age, sex, BMI, smoking) and multivariable regression were used to account for confounding. Logistic regression and ROC analyses evaluated the prediction of BK persistence. Results: Compared with controls, TB patients had substantially lower baseline protein C and free protein S levels, and higher D-dimer levels (all p &lt; 0.001). In matched multivariable models, TB status remained independently associated with lower baseline natural anticoagulant levels. Lower baseline protein C and free protein S clustered with higher inflammatory markers and higher bacillary burden, and independently predicted BK persistence at 2 and 6 months (OR per 1%-point increase ~0.93\u20130.95 for protein C and ~0.92\u20130.94 for free protein S; all p &lt; 0.001). Discrimination for BK persistence was high (AUCs ~0.88\u20130.89). Lower baseline levels of natural anticoagulants were also associated with greater residual CT abnormalities at 6 months. PE cases had significantly lower protein C and free protein S than PE-free patients. Conclusions: Active pulmonary TB is associated with marked depletion of protein C and free protein S. Baseline reductions identify patients with higher inflammatory\/coagulation activation, higher bacillary burden, delayed microbiological clearance, more residual CT disease, and PE, supporting their potential role as adjunct risk-stratification biomarkers.<\/jats:p>","DOI":"10.3390\/jcm15051903","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:06:56Z","timestamp":1772460416000},"page":"1903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hypercoagulability in Pulmonary Tuberculosis: Reduced Protein C and Free Protein S Predict Pulmonary Embolism\u2014Evidence from a Prospective Romanian Cohort"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5130-6757","authenticated-orcid":false,"given":"Denisa Maria","family":"Mitroi","sequence":"first","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3856-7917","authenticated-orcid":false,"given":"Silviu Gabriel","family":"Vlasceanu","sequence":"additional","affiliation":[{"name":"Department of Physiology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Thoracic Surgery, Marius Nasta Pneumology Institute, 050159 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3510-3838","authenticated-orcid":false,"given":"Ovidiu Mircea","family":"Zlatian","sequence":"additional","affiliation":[{"name":"Microbiology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Olteanu","sequence":"additional","affiliation":[{"name":"Pneumology Department, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9976-2256","authenticated-orcid":false,"given":"Oana Maria","family":"Catan\u0103","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2998-689X","authenticated-orcid":false,"given":"Radu Razvan","family":"Mititelu","sequence":"additional","affiliation":[{"name":"Microbiology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca Lelia","family":"Riza","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgiana","family":"Camen","sequence":"additional","affiliation":[{"name":"Radiology Department, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-6969","authenticated-orcid":false,"given":"Viorel","family":"Biciu\u0219c\u0103","sequence":"additional","affiliation":[{"name":"Pneumology Department, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6335-1627","authenticated-orcid":false,"given":"Ramona","family":"Cioboat\u0103","sequence":"additional","affiliation":[{"name":"Pneumology Department, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"ref_1","unstructured":"World Bank (2022). 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