From hypoxia to thrombosis: a hypothesis-driven framework for pulmonary embolism risk in deep underground environments

Pulmonary embolism (PE) is one of the most severe manifestations of venous thromboembolism, yet current diagnostic and preventive frameworks have largely been developed in ground-based clinical settings. Deep underground environments represent complex occupational exposure systems characterized by relative hypoxia or oxygen fluctuation, normobaric to mildly hyperbaric pressure, high humidity and heat, airborne particulates, radon accumulation, restricted ventilation, limited mobility, circadian disruption, and enclosed psychosocial stress. These factors may interact dynamically with oxygen sensing, cardiopulmonary compensation, venous return, endothelial function, and coagulation-inflammation pathways. However, the relationship between deep underground exposure, thrombogenesis, PE recognition, and prevention remains insufficiently conceptualized. Direct epidemiological evidence linking deep-underground occupational exposure to incident venous thromboembolism or PE remains scarce, and existing PE prediction tools have not been specifically validated in deep-underground occupational populations. Therefore, this review does not assume that underground exposure independently increases PE incidence or that established clinical tools are inadequate. Instead, we develop a hypothesis-driven framework to examine whether exposure-related factors-including oxygen fluctuation, heat and dehydration, restricted mobility, altered hemodynamics, and inflammatory stress-could modify thrombotic susceptibility, symptom interpretation, or the operational performance of conventional PE pathways. We summarize the environmental and physiological stressors relevant to PE, examine how they may amplify Virchow's triad, and discuss research questions concerning symptom recognition, anticoagulation, reperfusion decision-making, preventive interventions, and the staged development of dynamic risk warning models. This review aims to provide a conceptual foundation for future surveillance, prevention, and clinical research on PE in deep underground occupational populations.