Abstract 17907: Challenges of Anticoagulation during Cardiopulmonary Bypass in Children: Impact of Low Antithrombin Levels

Abstract

Introduction: Heparin-based anticoagulation in children is challenging as they have a high prevalence of heparin resistance. Antithrombin, one of the main natural anticoagulant inhibitors that potentiate heparin anticoagulation activity, might be a critical component of heparin response and anticoagulation effectiveness. Objectives: Determine the impact of antithrombin levels on anticoagulation (heparin sensitivity and effectiveness) during cardiopulmonary bypass (CPB) in children <1 year old. Methods: Secondary analysis of a randomized controlled trial of individualized vs weight based heparin management in 90 infants <1-year-old undergoing cardiac surgery. All analyses combined both patient groups and were used linear regression models. Results: As expected, older patients had higher blood antithrombin levels (relative increase of 16±6% for patients >6 months old vs. those <6 month old, p=0.009). Response to heparin, reflected by change in anti-Xa levels from baseline after the initial heparin bolus (a laboratory measure of heparin sensitivity), was highest in patients with higher baseline antithrombin circulating levels (top tier: +0.94(0.16) U/ml per 100U/kg heparin vs. middle tier: +0.89(0.19) U/ml vs. lowest tier: +0.77(0.20) U/ml, p<0.001). Those patients with very low antithrombin levels during CPB (<0.35U/ml) had much greater heparin requirements (+165(30) U/kg/hr representing an increase of 243%, p<0.001) indicating greater heparin resistance. Insufficient anticoagulation on bypass (as measured by end of bypass anti-Xa level) was associated with higher clotting potential, reflected by higher plasma levels of thrombin-antithrombin complexes (+4.8(2.4) ng/ml per anti-Xa U/ml, p=0.05), and prothrombin activation fragment 1.2 (+85(32) pg/ml per anti-Xa U/ml, p=0.008). Moreover, lower circulating antithrombin level was associated with increased D-dimer levels after CPB (+53(25) ng/ml per 0.1 U/ml antithrombin, p=0.03). Conclusions: Low antithrombin level is associated with resistance to heparin and decreased anticoagulation activity, ultimately leading to lower ability to suppress thrombin generation during CPB. Antithrombin supplementation may potentially individualize and improve anticoagulation.