Subchronic lead inhalation changes clot structure, increases platelet aggregation and D-dimer levels in mice.

Lead (Pb) remains one of the major environmental contaminants and affects multiple systems. Nevertheless, the impact of inhaled Pb exposure on the hemostatic system remains poorly understood. In this research, we evaluated the effects of subchronic lead inhalation on platelet count and activity, D-dimer levels, and clot structure in a murine model. Forty male CD-1 mice were exposed to nebulized particles of lead acetate (5μg/m3) or vehicle (saline solution 0.9%) twice weekly for 8 weeks. We measured platelet count using an automated counter, ADP-induced platelet aggregation using optical methods, plasma D-dimer levels by ELISA, and clot ultrastructure by scanning electron microscopy, and analyzed these at different time points (2, 4, 6, and 8 weeks). Femur Pb concentrations were measured at 8 weeks as evidence for Pb absorption and accumulation. Platelet counts were similar between the study groups. However, Pb exposure generated a biphasic platelet response: decreased function in weeks 2 and 4, followed by increased aggregation in weeks 6 and 8. In Pb-exposed mice, plasma D-dimer levels were significantly elevated compared with controls at weeks 6 and 8. Ultrastructural analysis showed a more compact fibrin mesh with thinner fibers and less space between them. These findings suggest subchronic Pb inhalation changes platelet responsiveness and fibrin clot structure, consistent with a prothrombotic phenotype. Since thrombosis, thrombin generation, and fibrinolytic resistance were not directly measured, these results should not be interpreted as proof that Pb caused an in vivo thrombosis event.