Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review
1 Division of Hematology, University of British Columbia, Vancouver General Hospital, 855 12th Ave W, Vancouver, BC V5Z 1M9, Canada
2 Divisions of Pediatric Infectious Disease and Critical Care, University of Toronto, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
3 McLaughlin-Rotman Centre for Global Health, University Health Network, 101 College Street, Suite 406 Toronto, ON M5G 1L7, Canada
4 Department of Medicine, University of Toronto, 1 King's College Circle Medical Sciences Building-Room 2109, Toronto, ON M5S 1A8, Canada
5 Interdepartmental Division of Critical Care Medicine, University of Toronto, Queen Street Wing, Room 4-042, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Critical Care 2012, 16:R7 doi:10.1186/cc11145Published: 16 January 2012
A strong biologic rationale exists for targeting markers of endothelial cell (EC) activation as clinically informative biomarkers to improve diagnosis, prognostic evaluation or risk-stratification of patients with sepsis.
The objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis. MEDLINE was searched for publications using the keyword 'sepsis' and any of the identified endothelial-derived biomarkers in any searchable field. All clinical studies evaluating markers reflecting activation of ECs were included. Studies evaluating other exogenous mediators of EC dysfunction and studies of patients with malaria and febrile neutropenia were excluded.
Sixty-one studies were identified that fulfilled the inclusion criteria. Overall, published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis, supporting the critical role of EC activation in sepsis. Multiple studies also reported positive associations for mortality and severity of illness, although these results were less consistent than for the presence of sepsis. Very few studies, however, reported thresholds or receiver operating characteristics that would establish these molecules as clinically-relevant biomarkers in sepsis.
Multiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans, and variably correlated to other clinically-important outcomes. The clinical utility of these biomarkers is limited by a lack of assay standardization, unknown receiver operating characteristics and lack of validation. Additional large-scale prospective clinical trials will be required to determine the clinical utility of biomarkers of endothelial activation in the management of patients with sepsis.