ADP-dependent platelet activation is required for thrombus formation during a long-distance flight

The association between venous thromboembolism (VTE) and air travel is well documented. Prolonged exposure to reduced atmospheric pressure and low oxygen levels during flights triggers coagulation disorders, representing the primary risk factor for Deep Vein Thrombosis (DVT), surpassing immobility. In our study, we investigated how long-distance flight conditions affect VTE development in mice exposed to 6h of hypobaric hypoxia or normobaric normoxia after inferior vena cava (IVC) ligation. We observed a pro-thrombotic profile under flight-simulated conditions, characterized by larger thrombi with higher neutrophil and fibrin densities. However, no difference was observed in neutrophil extracellular traps (NETs) or fibrin-positive neutrophils in thrombi between groups, indicating that neutrophils/NETs may not be involved in DVT development during flight. Considering the elevated ADP levels observed at high altitudes, we further assessed thrombus formation in wild-type and P 2 RY 12 -deficient mice. Remarkably, thrombus formation was no longer affected by aircraft conditions in P 2 RY 12 -deficient or wild type mice treated with clopidogrel. We conclude that ADP-induced platelet activation is involved in the development of DVT during flight, suggesting that the use of P 2 RY 12 inhibitors may be of interest to prevent DVT in susceptible patients.