Introduction: Cell free DNA (cfDNA) is released into the circulation in the setting of various pathological states and is linked with morbidity, including systemic inflammation (SIRS) and thrombosis. We aimed to characterize cfDNA levels in children after cardiopulmonary bypass (CPB) and its association with SIRS, thombosis and other clinical outcomes.
Hypothesis: 1. CPB results in elevated cfDNA proportionate to the severity of SIRS. 2. Higher cfDNA is associated with increased thrombosis and other morbidity.
Methods: The entire cohort consisted of children (<18 years) undergoing CPB. Blood was sampled pre/post CPB, at ICU admission and q6h to max 72h and analyzed for cfDNA and cytokines (IL1α, IL6, IL8, IL10, and TNFα). The relationship between cfDNA and cytokines was assessed by canonical correlation. Systematic vascular ultrasounds were completed in a subset of patients co-enrolled in a prospective study of thrombotic complications after CPB. Association between cfDNA and thrombosis in this subset was examined using canonical discrimination.
Results: The 200 patients in the full cohort tended to be female (58%) at a median (IQR) age 0.6 (0.3-3.4) years, with a mean CPB time of 121 ± 61 minutes. Mean (±SD) cfDNA was 5 ± 2.3 μg/mL at baseline, and remained unchanged throughout whereas cytokines peaked by 3 hours, decreasing toward baseline by 72h. cfDNA was associated with all cytokines, but was strongest with IL6 (r=0.66, p<0.001). A weak association was found between predictors and composite morbidity score (cfDNA r=0.06, p<0.001). Vascular ultrasounds were available for 39 subjects, 36% (n=14) of whom had ≥ 1 thrombotic complication. Thrombosis was directly associated with postoperative cfDNA and cytokine levels; the association was strongest with cfDNA (r=0.60, p <0.001) and IL8 (r=0.48, p<0.001).
Conclusions: Elevated cfDNA after CPB is associated with thrombotic complications and may represent a future target for investigation and intervention.