PB0966 - Effects of per- and polyfluoroalkyl substances (PFAS) on thrombosis and haemostasis

Background: Per- and polyfluoroalkyl substances (PFAS) have aroused as prevalent environmental contaminants due to their low degradation, ubiquitous occurrence, and multiple negative human health outcomes such as immunotoxicity, cytotoxicity, hepatotoxicity, reproductive toxicity, developmental toxicity, and cardiotoxicity. Platelets are the main actors in thrombosis and hemostasis but exposure to PFAS such as PFTA (perfluorotetradecanoic acid), and PFOA (perfluorooctanoic acid, contains lesser six -CF2- groups than the former) incur thrombocytopenia and cardiovascular diseases, however, the exact underlying mechanism has not yet been elucidated.

Aims: To explore the effects and underlying mechanisms of PFTA and PFOA on thrombosis and hemostasis.

Methods: The effects of PFAS on platelet aggregation were measured using light-transmission aggregometry with platelets from healthy volunteers. Platelet activation markers (P-selectin, Pac-1, and Annexin-V) were assessed by flow cytometry. Using thromboelastography, we determined the coagulation activity. Furthermore, perfusion chamber and deep-vein thrombosis (DVT) model were employed to evaluate thrombus formation, in vitro and in vivo, respectively.

Results: PFTA induced platelet secretion, integrin activation and platelet aggregation in a dose-dependent manner and blockade by GPIbα antibody (Fab fragment). PFOA conversely, inhibited platelet activation and aggregation, especially induced by PFTA. PFTA has procoagulation activity as was corroborated by platelet phosphatidylserine exposure, clot retraction, and thromboelastography. In-vivo findings in the DVT model further supported PFTA-induced platelet activation and thrombus formation in mice while PFOA notably deterred thrombosis. Interestingly, aspirin efficiently inhibited PFTA-mediated thrombus formation.

Conclusion(s): The increased blood coagulation and thrombosis by PFTA might be attributed to the presence of additional six -CF2- groups as compared to PFOA. However, GPIbα and coagulation cascade may be involved in the PFAS-mediated coagulation, platelet aggregation, and venous thrombosis. Our findings underscore that appropriate antiplatelet drugs can effectively prevent PFAS-mediated hypercoagulable state.