An Insight Into a Potential Antithrombin-Independent Mechanism of Inadequate Heparin Response in Neonates and Infants Undergoing Pediatric Cardiac Surgery: An Exploratory Study

J Cardiothorac Vasc Anesth. 2026 May 26:S1053-0770(26)00459-3. doi: 10.1053/j.jvca.2026.05.058. Online ahead of print.

Abstract

Objectives: Inadequate heparin response is frequently observed in neonates and young infants. While low antithrombin level is considered to be the primary cause, the existing literature suggests that it is not necessarily responsible. However, granular coagulation factor profiling data are rather limited.

Design: Prospective, single-center study.

Setting: Tertiary academic hospital in the United States.

Participants: Total of 30 neonates and infants who underwent cardiac surgery with cardiopulmonary bypass between May 31, 2022, and February 22, 2023.

Interventions: None.

Measurements and main results: Comparison between the heparin response group and the inadequate heparin response group demonstrated that antithrombin levels were comparable. However, levels of another thrombin inhibitor, α2-macroglobulin, and coagulation factor adjunct protein S were significantly lower in the inadequate heparin response group.

Conclusions: Lower α2-macroglobulin and protein S levels may be at least partly responsible for inadequate heparin response in the study cohort.

Keywords: antithrombin; heparin response; protein S; α(2)-macroglobulin.