Idiopathic pulmonary fibrosis (IPF) is strongly linked to an elevated risk of thrombotic events and mortality. This review examines the intricate relationship between pulmonary fibrosis and thrombosis, exploring epidemiological data, underlying mechanisms, and therapeutic approaches. A particular focus is placed on the role of extracellular vesicles (EVs) as mediators connecting fibrosis and coagulation. Coagulation factors actively drive fibrosis, while fibrosis induces thrombotic pathways, creating a self-perpetuating cycle. Retrospective studies suggest potential benefits of anticoagulants in IPF; however, prospective trials have faced significant challenges. Emerging therapies, including novel anticoagulants, profibrinolytic agents, and protease-activated receptor (PAR) inhibitors, show promise in preclinical and early clinical studies. EVs are identified as crucial contributors to interstitial lung disease (ILD) pathology, facilitating intercellular communication and promoting both fibrosis and coagulation. EV-based strategies, such as modulation, engineered EVs for drug delivery, and mesenchymal stem cell-derived EVs, hold potential as innovative treatments. Future research should focus on optimizing risk–benefit profiles, identifying predictive biomarkers, and integrating combination approaches targeting fibrotic, thrombotic, and inflammatory pathways. Understanding EVs’ role in ILDs could pave the way for targeted interventions and improved outcomes.
