Beta (β)-antithrombin activity in children and adults: implications for heparin therapy in infants and children

Abstract

Background: Antithrombin, a hemostatic protein and naturally occurring anticoagulant, is a major thrombin inhibitor. The capacity of antithrombin to inhibit thrombin is known to increase a 1000-fold whilst in the presence of unfractionated heparin. β-antithrombin is an isoform of antithrombin with a high affinity for unfractionated heparin. This study aimed to determine the differences in the anticoagulant activity of the β-antithrombin isoform in children compared with adults.

Methods: Plasma samples were obtained from 105 healthy individuals from the following age groups: neonates (day 1 and day 3), 28 days to 1 year, 1-5 years, 6-10 years, 11-16 years and adults. The method utilized to measure the activity of β-antithrombin in plasma is a modified version of the total antithrombin assay routinely used in diagnostic laboratories. The modified version of this assay allows for the specific quantification of the β-antithrombin glycoform anticoagulant activity alone, as the β-antithrombin molecule is activated under a high salt concentration, which in turn does not allow activation of other antithrombin isoforms.

Conclusions: This study demonstrated that there are no age-specific differences in the activity of β-antithrombin. However, considering that the total AT activity is significantly reduced in neonates, our results suggest that in this population β-antithrombin activity is a major contributor to the overall activity of AT.

Keywords: anticoagulants; antithrombin III; blood coagulation factors; heparin; pediatrics.