Our present study shows that the levels of endothelial-derived EVs carrying PDI are significantly elevated in the plasma of DVT mice, and GPIIb/IIIa on the surface of activated platelets or thrombi is significantly increased, whereas PDI inhibition results in a reduction in the activation levels of endothelial-derived EVs carrying PDI and GPIIb/IIIa. Here, P4HB is linked to deep vein thrombosis.