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Antithrombin activity and heparin response in neonates and infants undergoing congenital cardiac surgery: a
Vannessa M Chin1, Marie-Laure Laskine Holland1, Marlee M Parker1
1The Hospital for Sick Children, Toronto, ON, Canada.
Insights
Infants and neonates undergoing heart surgery show similar heparin responsiveness despite differing antithrombin (AT) levels. Preoperative AT activity can help predict heparin response in children outside the neonatal period.
Area of Science:
- Pediatric Cardiology
- Coagulation Science
- Anesthesiology
Background:
- The immature coagulation system in infants presents unique physiological differences affecting heparin responsiveness.
- Variations in heparin-enhanced thrombin inhibition are linked to age-related protein levels, impacting anticoagulant therapy efficacy.
- Understanding these differences is crucial for optimizing perioperative anticoagulation in pediatric cardiac surgery.
Purpose of the Study:
- To evaluate the relationship between preoperative antithrombin (AT) activity and heparin responsiveness in neonates and infants undergoing congenital cardiac surgery.
- To compare heparin responsiveness, measured by the heparin sensitivity index (HSI), between neonates and infants.
- To identify potential predictors of heparin resistance in pediatric patients.
Main Methods:
- Retrospective cohort study of 141 neonates (0-28 days) and infants (29-365 days) undergoing congenital cardiac surgery.
- Heparin response was primarily assessed using the heparin sensitivity index (HSI); heparin loading doses and resistance were secondary endpoints.
- Multivariable linear regression analyses were employed to determine the association between AT activity and HSI.
Main Results:
- A significant, moderate relationship was observed between antithrombin (AT) activity and heparin sensitivity index (HSI) (r = 0.44; P = 0.009) after adjusting for relevant factors.
- Despite significantly different mean AT activity levels between neonates (60%) and infants (84%), their median HSI values were similar (0.76 vs 0.89 sec·unit(-1)·kg(-1); P = 0.182).
- These findings indicate comparable heparin responsiveness between the two age groups, irrespective of their distinct AT activity levels.
Conclusions:
- A moderate correlation exists between preoperative antithrombin (AT) activity and heparin response (HSI) in pediatric cardiac surgery patients.
- Heparin responsiveness, as measured by HSI, is similar in neonates and infants, despite significant differences in their baseline AT activity.
- Preoperative AT activity may help identify children at risk for decreased heparin responsiveness, guiding perioperative exogenous AT administration, particularly in infants.
Purpose:
The immature coagulation system during infancy has age-related physiological differences in proteins that contribute to significant variation in heparin responsiveness through alterations in heparin-enhanced thrombin inhibition. The primary aim of this study was to evaluate the relationship between preoperative antithrombin (AT) activity and heparin responsiveness in neonates and infants undergoing congenital cardiac surgery.
Methods:
In this retrospective cohort study, neonates (aged 0-28 days) and infants (aged 29-365 days) undergoing congenital cardiac surgery in the 12-month period from October 2013 to 2014 were studied. The two age groups were compared for the primary endpoint of heparin response measured by the heparin sensitivity index (HSI), with heparin loading doses and heparin resistance being secondary endpoints. Multivariable linear regression analyses were used to explore the relationship between AT activity and heparin response measured by HSI.
Results:
There were 122 infants and 19 neonates included in the study. After adjusting for low-molecular-weight heparin, unfractionated heparin, and platelet count, there was a significant relationship between AT activity and HSI (r = 0.44; P = 0.009). The median [interquartile range] HSI did not differ between neonates and infants (0.76 [0.69- 0.98] vs 0.89 [0.70-1.10] sec·unit(-1)·kg(-1), respectively; median difference, 0.08; 95% confidence interval [CI], -0.01 to 0.17; P = 0.182), despite the mean (standard deviation) AT activity differing between age groups [60 (16)% vs 84 (18)%, respectively; mean difference, 24; 95% CI, 15 to 32; P < 0.001].
Conclusions:
There was a moderate relationship between AT activity and heparin response measured by HSI. Comparing neonates and infants, there was similar heparin responsiveness measured by HSI despite differing AT activity levels. These findings should help guide the perioperative administration of exogenous AT to neonates and infants and suggest that, outside the neonatal period, preoperative AT activity may be used to identify children at risk of decreased heparin responsiveness.
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