ADAMTS13 in pediatric sepsis: a prognostic biomarker with potential therapeutic implications

Abstract

Growing evidence implicates a pro-thrombotic state, caused by ADAMTS13 deficiency, in sepsis-associated organ dysfunction, but pediatric data is limited. Our purpose was to evaluate association of ADAMTS13 with prognosis of pediatric sepsis. This was prospective observational study, conducted on 70 children with sepsis and 18 healthy controls. Patients were classified upon Pediatric Intensive Care Unit (PICU) admission into sepsis, severe sepsis, and septic shock groups. Serum ADAMTS13 was measured within 24 h of admission. The primary outcome was all-cause PICU mortality. ADAMTS13 was lower among patients than controls [median and interquartile range (IQR): 1.30 (0.88–3.13ng/mL) vs. 6.00 (5.55–6.50 ng/mL); p < 0.001]. ADAMTS13 was lower in both severe sepsis and septic shock than sepsis [median (IQR): 0.90 (0.80–1.75 ng/mL); 1.0 ng/ml (0.90–1.20); and 2.80 (1.00–3.85ng/mL), p = 0.026 and 0.006 respectively]. ADAMTS13 was lower among non-survivors compared with survivors [median (IQR): 0.9 (0.80–1.18 ng/mL) vs. 2.45 (0.98–3.50 ng/mL); p < 0.001]. ADAMTS13 had area under Receiver Operating Characteristic Curve (AUC) of 0.77 for mortality prediction. Lower ADAMTS13 level was associated with mechanical ventilation; vasoactive medications; acute respiratory distress syndrome; and multiple organ dysfunction syndrome. ADAMTS13 correlated with pediatric Sequential Organ Failure Assessment (pSOFA) score (rs = -0.46, p < 0.001); vasoactive infusion days ((rs = -0.48, p < 0.001); and vasoactive-inotropic score on day1 (rs = -0.43, p < 0.001) and day2 ((rs = -0.41; p < 0.001). In pediatric sepsis, lower ADAMTS13 level is a risk factor for organ dysfunction and mortality, lending theoretical foundations to therapeutic interventions aiming at reversing the pro-thrombotic state in sepsis.