CD42-Enriched Extracellular Vesicles Contribute to Increased Platelet Aggregation and Possibly Organ Damage in...

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.

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.

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.

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.