Abstract Background Antithrombin is one of the main natural coagulation system inhibitors. It is potentiated by heparin, and may be a key component of heparin response, particularly in infants aged ...<1 year. We sought to determine the impact of baseline antithrombin activity on response to heparin and thrombin generation during cardiopulmonary bypass (CPB). Methods Secondary analysis was performed using linear regression analyses, which combined patients from a trial of individualized versus weight-based heparin management for 90 infants aged <1 year undergoing cardiac surgery. Results Mean baseline antithrombin activity was 0.69 ± 0.16 U/mL, and it was lower in neonates than in older infants (0.57 ± 0.15 vs 0.77 ± 0.12 U/mL; P < .001). Lower baseline antithrombin activity was associated with lower postheparin anti-Xa activity (EST SE: +0.47 (0.19) U/mL per 100 U/kg heparin; P = .01) and higher heparin doses during surgery (EST SE: +51 (17) U/kg per hour; P = .003). The administration of fresh frozen plasma attenuated the effect of low baseline antithrombin activity (interaction P value = .009). Patients with lower anti-Xa activity recorded during CPB had higher levels of thrombin-antithrombin complex (EST SE: +12.8 (4.7) ng/mL per −1 U/mL anti-Xa; P = .006); prothrombin activation fragment 1.2 (EST SE: +0.13 (0.07) log pg/mL per −1 U/mL anti-Xa; P = .06); and D-dimer (EST SE: −0.25 (0.09) log ng/mL per −1 U/mL anti-Xa; P = .009) in the postoperative period after adjustment for baseline antithrombin activity, duration of CPB, amount of fresh frozen plasma and heparin used throughout surgery in multivariable models. Conclusions Low circulating antithrombin activity is associated with lower heparin efficacy, which ultimately leads to a lower ability to suppress thrombin generation during CPB. Determination of risk factors for heparin resistance, and potentially, antithrombin replacement therapy, may individualize and improve anticoagulation treatment.
Objectives We sought to determine whether infants (younger than 1 year old) had similar clinical benefits with individualized anticoagulation management as older children and adult undergoing ...cardiopulmonary bypass (CPB). Background Individualized heparin and protamine management in older children and adults undergoing CPB has been associated with improved clinical outcomes. Methods Ninety infants younger than 1 year of age undergoing CPB were enrolled in a randomized, controlled trial comparing weight-based anticoagulation management using activated clotting time (ACT) to individualized management with Hemostasis Management System Plus. Manufacturer's guidelines were followed for the first 33 patients. A modified protocol was used for the last 57 patients with adjustments for coagulation system immaturity and hemodilution on CPB. Results The hemostasis management system (HMS) device consistently underestimated plasma anti-Xa levels, leading to an overestimated required heparin dose. After a blinded interim analysis revealed poor outcomes in the experimental HMS group using manufacturer guidelines, the safety committee suspended the study pending protocol modifications. The use of the HMS device following the modified protocol resulted in more stable anti-Xa levels during CPB with improved post-operative outcomes including reduced need for transfusions (71 ml/kg vs. 80 ml/kg; p = 0.003), ventilation time (33 h vs. 49 h; p = 0.04), intensive care (88 h vs. 99 h; p = 0.003), and hospital length of stay (192 h vs. 216 h; p < 0.001), compared with the weight-based protocol. Conclusions This study supports the use of the HMS device, with a modified protocol for infants younger than 1 year of age, for anticoagulation management during CPB. Clinical guidelines for the use of the HMS device should be modified for infants younger than 1 year of age.
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