Sepsis prediction in critically ill patients by platelet activation markers on ICU admission: a prospective pilot study

Background: Platelets have been involved in both surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with predisposition to sepsis in critical illness remains unknown. The aim of this work was to identify platelet markers that could predict sepsis occurrence in critically ill injured patients.
Results: This single-center, prospective, observational, 7-month study was based on a cohort of 99 non-infected adult patients admitted to ICUs for elective cardiac surgery, trauma, acute brain injury and post-operative prolonged ventilation and followed up during ICU stay. Clinical characteristics and severity score (SOFA) were recorded on admission. Platelet activation markers, including fibrinogen binding to platelets, platelet membrane P-selectin expression, plasma soluble CD40L, and platelet-leukocytes aggregates were assayed by flow cytometry at admission and 48h later, and also at the time of sepsis diagnosis (Sepsis-3 criteria) and 7 days later for sepsis patients. Hospitalization data and outcomes were also recorded. Of the 99 patients, 19 developed sepsis after a median time of 5 days. SOFA at admission was higher; their levels of fibrinogen binding to platelets (platelet-Fg) and of D-dimers were significantly increased compared to the other patients. Levels 48h after ICU admission were no longer significant. Platelet-Fg % was an independent predictor of sepsis (P = 0.030). By ROC curve analysis cutoff points for SOFA (AUC=0.85) and Platelet-Fg (AUC=0.75) were 8 and 50%, respectively. The prior risk of sepsis (19%) increased to 50% when SOFA was above 8, to 46% when Platelet-Fg was above 50%, and to 87% when both SOFA and Platelet-Fg were above their cutoff values. By contrast, when the two parameters were below their cutoffs, the risk of sepsis was negligible (3.8%). Patients with sepsis had longer ICU and hospital stays and higher death rate.
Conclusion: In addition to SOFA, platelet-bound fibrinogen levels assayed by flow cytometry within 24h of ICU admission help identifying critically ill patients at risk of developing sepsis.