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J Thorac Cardiovasc Surg. 2016 Feb;151(2):444-50. doi: 10.1016/j.jtcvs.2015.10.003. Epub 2015 Oct 9.

Challenges with heparin-based anticoagulation during cardiopulmonary bypass in children: Impact of low antithrombin activity.

Author information

1
Labatt Family Heart Centre, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
2
Division of Haematology/Oncology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
3
Division of Pediatric Hematology/Oncology, Department of Pediatrics, McMaster University, McMaster Children's Hospital, Hamilton, Ontario, Canada.
4
Labatt Family Heart Centre, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: brian.mccrindle@sickkids.ca.

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.

KEYWORDS:

antithrombin; congenital heart disease; heparin; surgery; thrombosis

PMID:
26553458
DOI:
10.1016/j.jtcvs.2015.10.003
[Indexed for MEDLINE]
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