Abstract 18061: Supplementation to Treat Antithrombin Deficiency Improves Sensitivity to Heparin, Anticoagulation and Decreased Thrombogenecity in Neonates and Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass

Abstract

Introduction: Preoperative antithrombin (AT) deficiency is common in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB), and is associated with heparin resistance, difficulties achieving optimal intraoperative anticoagulation and post-operative thrombosis. Methods: We performed a pilot randomized trial of pooled human AT supplementation for children <1 year with preoperative AT <0.85U/ml. Subjects received a split (patient and CPB prime) dose of AT before heparinization. AT was dosed to reach a predicted AT activity of 1.2U/ml during CPB calculated from preoperative AT level and patient weight. Results: We randomized 18 subjects; 17 completed the study (9 controls, 8 AT). Mean preoperative AT level was similar between groups (Control: 0.65±0.10 vs. AT: 0.68±0.15 U/mL, p=0.66). AT group subjects had higher AT than controls immediately after start of CPB (Control: 0.44±0.10 vs. AT: 1.15±0.20 U/mL, p<0.001) and at the end of CPB (Control: 0.67±0.14 vs. AT: 1.19±0.16 U/mL, p<0.001). AT supplementation was associated with increased activated clotting time (ACT) post-heparinization (Control: 500±72 vs. AT: 639±172 seconds, p=0.02), increased heparin sensitivity (Control: 89±23 vs. AT: 114±22 ACT seconds per 100U/kg heparin, p=0.02), and decreased heparin dose given during CPB (Control: 1126±344 vs. AT: 845±165 U/kg, p=0.03). After primary heparinization, 56% of control subjects did not achieve ACT target vs. 25% of AT subjects. At the end of CPB, AT group subjects had lower prothrombin levels (Control: 746±372 vs. AT: 460±102 ng/mL, p=0.02) and lower levels of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8 and TNFα). Supplementation with AT was not associated with increased chest tube volume loss or blood product requirements. One subject in each group had severe bleeding, and one in each group had post-operative infection. Thrombosis was noted for 3 controls and 1 AT subjects. Conclusions: AT supplementation to treat preoperative AT deficiency in young children is associated with decreased heparin resistance, improved anticoagulation and decreased thrombogenecity. Safety profile regarding bleeding and infections appears favorable. Equipoise exists for a larger definitive outcome trial.