Endothelial Microparticles as a Biomarker for Diagnosis and Prognosis in Early Sepsis

Study Summary

Sepsis is a major global health problem, leading to substantial morbidity and mortality despite medical care. The initial diagnosis of sepsis is a clinical challenge, as it is based on nonspecific systemic criteria. Excessive endothelial activation is a cardinal feature of sepsis and contributes to microvascular leak, edema, circulatory shock and organ failure. Activated endothelial cells shed endothelial microparticles (EMPs) which can be measured in plasma and are found at low levels in healthy subjects. Elevated EMPs have been reported in sepsis, but whether their effect is beneficial or deleterious is unclear. In this context, we hypothesize that circulating EMP levels can be assessed as a biomarker differentiating sepsis from non-sepsis critical illness. This may also suggest that EMP levels correlate with 30-day mortality. We propose to measure circulating EMPs at ICU admission in subjects with suspected sepsis. Final diagnoses will be adjudicated using standard criteria and 30-day mortality ascertained. Subjects determined not to have sepsis will serve as the control group. EMP levels will be correlated with diagnosis to ascertain the utility of EMP levels as a diagnostic biomarker for sepsis. For those subjects with proven sepsis, EMP levels will be correlated to 30-day mortality to assess EMP level as a prognostic marker in sepsis.

Primary Outcome

To evaluate the hypothesis that EMP level is a predictive biomarker for the diagnosis of sepsis. For the primary objective, a prospective, cross-sectional, case control design will be utilized. EMP levels will be measured at ICU admission in subjects with physician-suspected sepsis. For each subject, the final diagnosis of sepsis or non-sepsis critical illness will be adjudicated using standard criteria, and the subjects determined to have sepsis will serve as the cases while those subjects with

Conditions Studied

Study Locations (2)