DOI: 10.3390/ijms27135927 ISSN: 1422-0067

Does Tuberculosis Leave a Thromboinflammatory Memory After Cure? A Narrative Review with a Conceptual Framework on Hypercoagulability, Cellular Reservoirs, and Extracellular Vesicle Signaling

Ramona Cioboata, Silviu Gabriel Vlasceanu, Maria-Loredana Tieranu, Eugen Nicolae Tieranu, Mara Amalia Balteanu, Denisa Maria Mitroi, Anca Lelia Riza, Simona Daniela Neamtu, Adina Andreea Mirea

(TB) induces a pronounced thromboinflammatory state during active disease, characterized by elevated fibrinogen, D-dimer, and thrombin-related activity, reduced levels of endogenous anticoagulants, impaired fibrinolysis, platelet activation, and endothelial dysfunction. Although many of these abnormalities improve after treatment initiation, accumulating evidence suggests that microbiological cure may not fully restore vascular, immune, and hemostatic homeostasis. This raises the possibility that TB leaves a persistent thromboinflammatory imprint after cure. This narrative synthesizes current evidence on tuberculosis-associated hypercoagulability during active disease and after treatment, and proposes a conceptual framework for post-tuberculosis thromboinflammatory memory grounded in cellular persistence, tissue remodeling, and extracellular vesicle-mediated signaling. Candidate storage compartments include hematopoietic stem and progenitor cells, monocyte/macrophage lineages, alveolar macrophages, remodeled pulmonary endothelium, and fibrotic post-TB lung tissue. EVs may function as mobile vectors that transfer procoagulant phospholipids, tissue factor, inflammatory proteins, and regulatory microRNAs between these compartments, thereby linking local post-TB remodeling to systemic vascular and coagulation pathways. A mechanistic evidence ladder is proposed, encompassing phenotypic persistence, EV cell-of-origin attribution, molecular persistence, paired longitudinal validation, functional transfer, and clinical outcome linkage. Current data support the biological plausibility of this framework but remain insufficient to establish post-TB thromboinflammatory memory as a defined clinical entity. Direct evidence in long-term TB survivors is still lacking, particularly with respect to persistent EV signatures, cell-specific reservoirs, and the functional transfer of procoagulant phenotypes. Longitudinal, cell-resolved, multi-omic, and functionally validated studies are required to determine whether TB leaves a durable thromboinflammatory memory, where it is stored, and whether it contributes to long-term thrombotic and cardiovascular risk. This article should be interpreted as a narrative review with a conceptual framework rather than as evidence that post-tuberculosis thromboinflammatory memory is already a formally established clinical entity.

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