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Challenges with heparin-based anticoagulation during cardiopulmonary bypass in children: Impact of low antithrombin
Cedric Manlhiot1, Colleen E Gruenwald1, Helen M Holtby1
1Labatt Family Heart Centre, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Low antithrombin activity in infants undergoing cardiopulmonary bypass reduces heparin effectiveness, increasing thrombin generation. Identifying risk factors and considering antithrombin replacement may improve anticoagulation therapy.
Area of Science:
- Pediatric Cardiology
- Hematology
- Coagulation Science
Background:
- Antithrombin is a key natural inhibitor of the coagulation system.
- Heparin potentiates antithrombin activity, crucial for anticoagulation in infants <1 year.
- Baseline antithrombin levels may influence heparin response during cardiopulmonary bypass (CPB).
Purpose of the Study:
- To investigate the impact of baseline antithrombin activity on heparin response.
- To assess the effect of antithrombin levels on thrombin generation during CPB in infants.
Main Methods:
- Secondary analysis of data from 90 infants (<1 year) undergoing cardiac surgery.
- Linear regression models were used to analyze the relationship between antithrombin activity, heparin response, and thrombin generation markers.
Main Results:
- Lower baseline antithrombin activity was linked to reduced anti-Xa activity and increased heparin requirements.
- Fresh frozen plasma administration partially mitigated the effects of low antithrombin.
- Lower anti-Xa activity correlated with increased thrombin-antithrombin complex, prothrombin fragment 1.2, and D-dimer levels post-CPB.
Conclusions:
- Low antithrombin activity impairs heparin efficacy and reduces the ability to control thrombin generation during CPB.
- Identifying heparin resistance risk factors and exploring antithrombin replacement could personalize anticoagulation strategies.
- Optimizing anticoagulation in infants undergoing CPB may improve clinical outcomes.
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.
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