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 w hether plasma thrombomodulin concentrations are associated with the ex tent of multiple organ system failure and mortality. Design: Prospecti ve, cohort study. Setting: Pediatric intensive care unit. Patients: Tw enty-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 on ce 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 enzy me-linked immunosorbent assay. Septic shock nonsurvivors had significa ntly greater mean thrombomodulin concentrations (10.6 +/- 2.2 ng/mL) t han septic shock survivors (5.5 +/- 0.6 ng/mL) (p < .05) and healthy c ontrol patients (3.4 +/- 0.2 ng/mL) (p < .01). Mean thrombomodulin val ues increased as the number of organ system failures increased. Conclu sions: Pediatric survivors and nonsurvivors of septic shock have circu lating thrombomodulin concentrations 1.5 and 3 times greater than heal thy control patients, These findings likely represent sepsis induced e ndothelial injury. Patients with multiple organ system failure have ci rculating thrombomodulin concentrations which are associated with the extent of organ dysfunction. We speculate that measurement of plasma t hrombomodulin concentrations in septic shock may be a useful indicator of the severity of endothelial damage and the development of multiple organ system failure.