{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:02:46Z","timestamp":1774940566344,"version":"3.50.1"},"reference-count":149,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Pulmonary diseases increasingly reshape vascular biology and coagulation beyond the lung. Across acute infections and acute respiratory distress syndrome (ARDS), chronic airway inflammation (e.g., COPD), sleep-disordered breathing, fibrotic interstitial lung disease, and particulate air pollution, convergent immune programs couple inflammation to coagulation through immunothrombosis. Physiologic immunothrombosis can confine pathogens within the microvasculature, but dysregulated thromboinflammation drives endotheliopathy, platelet\u2013leukocyte cooperation, neutrophil extracellular trap (NET) formation, complement activation, tissue factor\u2013thrombin signaling, and fibrinolytic shutdown, culminating in microvascular thrombosis and organ injury. Emerging clinical and translational data suggest that these same modules may reshape stroke biology: NET-rich thrombi are linked to recanalization failure and thrombolysis resistance; systemic endotheliopathy can destabilize the blood\u2013brain barrier and promote no-reflow; and complement\u2013coagulation crosstalk amplifies neurovascular injury. Beyond acute events, chronic microvascular thrombosis and blood\u2013brain barrier leakage allow fibrin(ogen) and coagulation proteases to signal through microglia and protease-activated receptors, potentially coupling vascular dysfunction to cognitive decline and neurodegenerative trajectories. Here we integrate convergent but independently derived evidence from pulmonary medicine, coagulation biology, stroke pathology, and neurodegeneration research into a lung-to-brain immunothrombosis framework. Because these evidence streams have developed largely in parallel, this synthesis represents a mechanistic integration hypothesis\u2014intended to identify shared therapeutic nodes and guide cross-disciplinary validation\u2014rather than a demonstrated biological sequence. We outline biomarker-guided strategies that pair conventional antithrombotics with targeted anti-thromboinflammatory approaches (NET-, complement-, and endothelial\/adhesion-directed) while managing bleeding risk.<\/jats:p>","DOI":"10.3389\/fphar.2026.1811794","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:32:01Z","timestamp":1774935121000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The immunothrombosis pathway linking pulmonary disease to stroke and neurodegeneration: mechanisms and therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Aiping","family":"Zou","sequence":"first","affiliation":[{"name":"The First People\u2019s Hospital of Jiashan, Jiashan Hospital Affiliated to Jiaxing University, Jiaxing","place":["Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"You","sequence":"additional","affiliation":[{"name":"The First People\u2019s Hospital of Jiashan, Jiashan Hospital Affiliated to Jiaxing University, Jiaxing","place":["Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Xiao","sequence":"additional","affiliation":[{"name":"The First People\u2019s Hospital of Jiashan, Jiashan Hospital Affiliated to Jiaxing University, Jiaxing","place":["Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e208","DOI":"10.1017\/S0950268822001480","article-title":"Renal, cardiac, neurological, cutaneous and coagulopathic long-term manifestations of COVID-19 after recovery; a review","volume":"150","author":"Afrisham","year":"2022","journal-title":"Epidemiol. 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