(890) Reduced ADAMTS13 Response in Pediatric Surgical Sepsis

Introduction: Surgical stress elicits a host immune response that frequently results in inflammation and immune depression. Little is known about the pediatric host response to sepsis following surgical stress compared to the sepsis host response without surgical stress.

Methods: This is a secondary analysis from the Phenotyping of Pediatric Sepsis and Multiple Organ Failure (PHENOMs) study, a prospective multicenter observational study of severe pediatric sepsis from 9 US intensive care units. We compared baseline characteristics and 34 blood inflammatory markers with 24h of enrollment between children with surgical and non-surgical sepsis. Multivariate logistic regression for the association of baseline characteristics and inflammatory markers with surgical sepsis was performed.

Results: Among 400 children studied, 49 had surgical sepsis and 351 had non-surgical sepsis. There were no differences in baseline patient characteristics (age, sex, race, ethnicity, any preexisting condition, history of immune compromised state, or new trauma). These groups did not differ in mortality (14% surgical, 10.5% non-surgical). In comparing host inflammatory response in univariate analysis, children with surgical sepsis showed differential levels with: decreased ADAMTS13 with median value of 58.0 (IQR 41.5 – 81.5) v 72.0 (57.5 – 89.0) p-value < 0.001, decreased TRAIL 32.9 (24.2 – 40.4) v 37.9 (29.1 – 55.4) p-value < 0.001, increased IL-22 29.5 (24.8 – 40.1) v 24.8 (20.1 – 34.2) p-value = 0.007, decreased CXCL10 497.2 (277.3 – 1159.7) v 771.2 (362.8 – 2236.9) p-value = 0.012, decreased soluble fas ligand 35.9 (25.2 – 59.9) v 46.7 (29.5 – 78.6) p-value = 0.019, increased ferritin 369.6 (184.5 – 657.1) v 199.5 (94.1 – 623.5) p-value = 0.037, and increased IL-8 65.5 (42.9 – 177.9) v 52.6 (31.4 – 99.9) p-value = 0.04. After adjustment for these inflammatory markers in multivariate analysis, only ADAMTS13 remained significantly associated with surgical status (OR 0.98, 95% CI 0.96-0.99).

Conclusions: In a cohort of critically ill children with sepsis, 45% of those with surgical sepsis had decreased ADAMTS13 activity potentially increasing the risk of thrombosis or thrombotic microangiopathy. These results suggest that further study of the impact of reduced ADAMTS13 activity in children with surgical sepsis is warranted.