Preclinical Models of Venous Thrombosis: A Critical Appraisal for Translational Research

CLINICAL PROBLEM: Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, affects ≈1 to 2 per 1000 individuals annually and represents a major cause of morbidity and mortality worldwide. Despite advances in anticoagulation therapy, significant gaps remain in understanding thrombosis resolution, postthrombotic syndrome, and identifying patients at risk for recurrence. Animal models are essential for mechanistic studies and preclinical drug development, yet their translational success has been inconsistent. Critical evaluation of available models is necessary to guide appropriate model selection and improve predictive validity. RECOMMENDATIONS: Select models by the primary biological question and the clinical scenario you want to mimic, then prespecify: (1) flow state (stasis versus reduced flow versus full flow), (2) injury (none/minimal versus chemical/thermal), and (3) end point modality (gross thrombus mass versus imaging volume versus molecular composition versus functional recanalization). Use at least 2 complementary models when claiming generality (eg, a reduced-flow model+a chemical injury model). SUMMARY: This review critically evaluates rodent, large animal, and cellular models of venous thrombosis, addressing their strengths, limitations, reproducibility challenges, and ability to incorporate clinically relevant variables. A comparative analysis with tabular summaries guides researchers in selecting appropriate models while highlighting gaps that must be addressed to improve translational outcomes.