Methodological and Pathophysiological Considerations in Obesity-Associated Thrombosis

Obesity is a major risk factor for both venous and arterial thrombosis, largely mediated by chronic oxidative stress and hemostatic dysregulation. Excess adipose tissue enhances the production of reactive oxygen species (ROS) from adipocytes and infiltrating macrophages, leading to lipid, protein, and DNA oxidation, reduced antioxidant capacity, and a pro-inflammatory milieu. These molecular alterations promote endothelial dysfunction, platelet hyperreactivity, hypercoagulability, and impaired fibrinolysis, creating a systemic prothrombotic state. Traditional coagulation assays provide limited insight into the dynamic process of thrombus formation under physiological flow. The Total Thrombus-Formation Analysis System (T-TAS) offers a microfluidic, flow-based platform that evaluates thrombus formation in whole blood under controlled shear conditions using collagen- or tissue factor-coated chips. T-TAS parameters, such as time to occlusion, area under the curve (AUC), and pressure kinetics, integrate platelet function, coagulation, and thrombus stability, providing a sensitive assessment of prothrombotic phenotypes. Combining oxidative stress biomarkers (e.g., malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and total antioxidant capacity) with T-TAS-derived functional readouts enables a multidimensional evaluation of thrombosis risk in obese individuals. This review highlights current evidence linking obesity-induced oxidative stress to hemostatic disturbances and illustrates the translational potential of the T-TAS for mechanistic studies and clinical risk stratification. Understanding the interplay between redox imbalance and thrombus formation under flow conditions may inform novel therapeutic strategies to prevent obesity-related thromboembolic events.