Increased circulating thrombomodulin in children with septic shock

Objectives: To test the hypothesis that children diagnosed with septic shock have increased plasma thrombomodulin values as a manifestation of microcirculatory dysfunction and endothelial injury; to determine whether plasma thrombomodulin concentrations are associated with the extent of multiple organ system failure and mortality. Design: Prospective, cohort study. Setting: Pediatric intensive care unit. Patients: Twenty-two children with septic shock and ten, healthy, control children. Interventions: Blood samples were obtained for plasma thrombomodulin determinations every 6 hrs for 72 hrs in septic shock patients and once in healthy control patients. Measurements and Main Results: Thirty-two children (22 septic shock, and 10 healthy controls) were enrolled in the study. Thrombomodulin concentrations were determined by an enzyme-linked immunosorbent assay. Septic shock nonsurvivors had significantly greater mean thrombomodulin concentrations (10.6 +/- 2.2 ng/mL) than septic shock survivors (5.5 +/- 0.6 ng/mL) (p < .05) and healthy control patients (3.4 +/- 0.2 ng/mL) (p < .01). Mean thrombomodulin values increased as the number of organ system failures increased. Conclusions: Pediatric survivors and nonsurvivors of septic shock have circulating thrombomodulin concentrations 1.5 and 3 times greater than healthy control patients, These findings likely represent sepsis induced endothelial injury. Patients with multiple organ system failure have circulating thrombomodulin concentrations which are associated with the extent of organ dysfunction. We speculate that measurement of plasma thrombomodulin concentrations in septic shock may be a useful indicator of the severity of endothelial damage and the development of multiple organ system failure.