Venous thromboembolism at high altitude: mechanisms, risk stratification, and precision prevention

High-altitude environments constitute an increasingly important global health concern as exposure widens. This narrative review summarizes recent evidence on the epidemiology, pathophysiology, and clinical therapy of venous thromboembolism (VTE) in high-altitude environments. Multi-system crosstalk mediated by hypoxia-inducible factor (HIF)-based activation disrupts hemostatic homeostasis, inducing a distinctive high-altitude prothrombotic phenotype. Traditional VTE clinical guidelines, designed mainly for low-altitude populations, show considerable weaknesses in high-altitude conditions. A new three-dimensional (altitude-exposure-susceptibility) risk assessment model is urgently required. Through comparative assessment of the evidence, we discuss fundamental controversies in this area, the need to create multidimensional predictive models combined with altitude-specific physiological variables, and suggest specific management approaches for high-risk groups. Currently, significant gaps exist in epidemiological data collection, mechanistic characterization, and clinical trial evidence. Future priorities include multi-omics integration, novel animal models, and rigorously designed randomized controlled trials to enable a paradigm shift from population-based to precision prevention of high-altitude VTE. Target audience: clinicians, physiologists, and public health researchers.