OBJECTIVE: To determine serum concentrations of thrombomodulin, the marker of endothelial injury, in patients with sepsis-induced disseminated intravascular coagulation and multiple organ dysfunction syndrome and to investigate the independent association between this marker and the development of disseminated intravascular coagulation, multiple organ dysfunction syndrome, and mortality.
DESIGN: A prospective cohort study.
SETTING: A 37-bed intensive care unit of a tertiary care hospital.
PATIENTS: One hundred consecutive patients with sepsis.
INTERVENTIONS: Serum thrombomodulin concentrations and the development of disseminated intravascular coagulation and multiple organ dysfunction syndrome were determined in patients on days 1 and 3 of sepsis. These data were used to determine an association between day 1 thrombomodulin concentrations and development of disseminated intravascular coagulation, multiple organ dysfunction syndrome, and mortality during intensive care unit stay. These connections were determined by the Cox proportional hazards model and plotting of receiver operating characteristic curves.
MEASUREMENTS AND MAIN RESULTS: Day 1 serum concentrations of thrombomodulin were higher in patients with disseminated intravascular coagulation (11.1 +/- 1.0 vs. 5.3 +/- 0.5 ng/mL; p < .0001) or multiple organ dysfunction syndrome (10.3 +/- 0.7 vs. 4.3 +/- 0.4 ng/mL; p < .0001) than those without, respectively. In patients with resolved disseminated intravascular coagulation (4.9 +/- 0.5 vs. 8.9 +/- 0.9 ng/mL, day 3 vs. day 1, p = .005) or multiple organ dysfunction syndrome (6.3 +/- 1.4 vs. 12.0 +/- 1.6 ng/mL, day 3 vs. day 1, p < .0001) on day 3 of sepsis, day 3 levels of thrombomodulin were down from day 1. Thrombomodulin concentration independently predicted the development of disseminated intravascular coagulation (hazard ratio 1.13, p < .0001), multiple organ dysfunction syndrome (hazard ratio 1.12, p < .0001), and mortality (hazard ratio 1.19, p < .0001) during intensive care unit stay. The area under the receiver operating characteristic curve showed that day 1 serum thrombomodulin levels had good discriminative power in predicting the development of disseminated intravascular coagulation (0.811), multiple organ dysfunction syndrome (0.896), and mortality (0.803) during intensive care unit stay.
CONCLUSIONS: Endothelial cell injury is critical in the progression from disseminated intravascular coagulation to multiple organ dysfunction syndrome and subsequent mortality in septic patients. Serum concentrations of thrombomodulin may be used in monitoring disseminated intravascular coagulation and multiple organ dysfunction syndrome in these patients.
