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The aim of this study was to explore the relative clinical and biomaterial effects of blood transfusions (Tx) and novel low-prime, surface-coated circuitry on perioperative outcome in a pediatric population undergoing cardiac surgery with cardiopulmonary bypass (CPB).Over a 12-month period, 80 patients weighing >10 kg undergoing ventricular septal defect (VSD) repair with CPB were prospectively randomized into two groups according to the type of CBP circuit used, then each randomized group was enrolled into two groups again, according to the need for transfusion (N=20): Group 1- Tx-free procedures on low-prime, surface-coated extracorporeal circuitry (FX05, Terumo); Group 2- procedures requiring Tx on coated circuitry; Group 3- Tx-free procedures with standard uncoated circuitry (D902, Sorin); Group 4 (Control)- procedures requiring Tx on uncoated circuitry. Blood samples were collected at baseline (T1), at the end of the CPB (T2) and 24 h (T3) postoperatively. rSO2 desaturation risk score >6000 (Invos, Somanetics) was calculated by multiplying rSO2 <50% by time.IL-6 levels (pg/ml) were significantly lower in Groups 1 and 3 versus control at T2 (13±4; 17±5 versus 33±8; p<0.05). CD11b/CD18 levels (%) were significantly lower in Group 1 (12±4) versus control (25±8) at T2 (p<0.05). Respiratory support time (h) was significantly less in Group 1 (11.4±6) versus control (19.8±7) (p<0.05). rSO2 desaturation risk >6000 (%) was 15.7±9 in Group 1 and 26.8±11 in control (p<0.05).Allogenic Tx amplifies the CPB-related inflammatory response. It is feasible to do congenital procedures safely without Tx for patients weighing >10 kg by using combined blood management strategies.