CD42-Enriched Extracellular Vesicles Contribute to Increased Platelet Aggregation and Possibly Organ Damage in Patients with Burn Injury Complicated by Sepsis

Background: Sepsis is the leading cause of death in patients with burn injury, in whom it represents a real diagnostic challenge. Here, we studied extracellular vesicles (EVs) released during sepsis in burn patients by multiplexed phenotyping and explored their role in promoting platelet aggregation. Methods: We enrolled 33 burn patients, 23 with (Burn Septic Patients–BSP) and 10 without sepsis (Burn Non-Septic Patients–BnSP), and 10 healthy subjects (HS). EVs, isolated by ultracentrifugation or precipitation-based methods, were characterized by Nanoparticle Tracking Analysis, Transmission Electron Microscopy, and flow cytometry, and their surface antigens studied by bead-based multiplex flow cytometry. Platelet aggregation was studied in platelet-rich plasma using light-transmission aggregometry. Results: EVs from BSP expressed a specific pattern of epitopes distinct from those from BnSP and HS. Specifically, EVs from BSP showed an increase in CD42a expression compared to BnSP-(p<0.05) and HS-(p<0.0001) derived EVs. Moreover, CD42a-EVs expression increased according to sepsis severity in BSP. In vitro, EVs from BSP, but not from HS, primed platelet aggregation, an effect reduced by an anti-CD42 neutralizing monoclonal antibody. Conclusion: Our results suggest the potential of CD42a-enriched EVs as diagnostic and prognostic markers of sepsis in burn patients and their role in increasing platelet activation in these patients.