Investigation into P2Y Receptor function in platelets from patients with sepsis.

Key underlying pathological mechanisms contributing to sepsis are hemostatic dysfunction and overwhelming inflammation. Platelet aggregation is required for hemostasis, and platelets are also separately involved in inflammatory responses that require different functional attributes. Nevertheless, P2Y receptor activation of platelets is required for this dichotomy of function. The aim of this study was to elucidate whether P2YR-dependent hemostatic and inflammatory functions were altered in platelets isolated from sepsis patients, compared to patients with mild sterile inflammation.Platelets from patients undergoing elective cardiac surgery (20 patients, 3 female), or suffering from sepsis following community acquired pneumonia (10 patients, 4 female) were obtained through the IMMunE dysfunction and Recovery from SEpsis related critical illness in adults (IMMERSE) observational clinical trial. in vitro aggregation and chemotaxis assays were performed with platelets after stimulation with ADP, and compared to platelets isolated from healthy control subjects (7 donors, 5 female). Cardiac surgery and sepsis both induced a robust inflammatory response with increases in circulating neutrophil counts with a trend towards decreased circulating platelet counts being observed. The ability of platelets to aggregate in response to ex vivo ADP stimulation was preserved in all groups. However, platelets isolated from patients with sepsis lost the ability to undergo chemotaxis towards N-formylmethionyl-leucyl-phenylalanine and this suppression was evident at admission through to, and including discharge from hospital.Our results suggest that P2Y1-dependent inflammatory function in platelets is lost in patients with sepsis resulting from community acquired pneumonia. Further studies will need to be undertaken to determine if this is due to localized recruitment to the lungs of a platelet responsive population, or loss of function as a result of dysregulation of the immune response.