Age‐specific differences in binding of heparin to plasma proteins

Abstract

Summary. Background: Clinically significant age-related differences in the anticoagulation effect of heparin have previously been established in vitro as well as in different clinical settings in vivo. These differences were hypothesized to be due to the age-specific differences in binding of heparin to plasma proteins. Objectives: The aim of this project was to investigate global agerelated differences in heparin binding to plasma proteins. Patients/Methods: Heparin-binding proteins were identified by incubating heparin-coated magnetic beads with plasma samples from neonates, children and adults, and purifying the proteins that were bound to the beads in this reaction system. Results: These results provide the first preliminary evidence of age-related differences in the total number and concentration of proteins bound to heparin. The results also suggest, for the first time, that there are age-related differences of heparin binding to antithrombin and thrombin. Conclusions: The results of this study, although preliminary, support and contribute to the explanation of the mechanism of age-related differences in the effect of heparin observed previously in vitro and in vivo.

Antithrombin activity and heparin response in neonates and infants undergoing congenital cardiac surgery: a retrospective cohort study

“…23 This is likely due to age-related differences in protein structures affecting the binding of heparin to plasma proteins. 1 The differences in heparin loading doses administered to neonates and infants reported here are consistent with the expected age-dependent effects of heparin, with neonates requiring larger heparin loading doses than infants. However, the heparin loading doses used in this study are larger than doses used in some other clinical studies investigating heparin responsiveness in children.…”

Effect of rivaroxaban, in contrast to heparin, is similar in neonatal and adult plasma

“…Allowing sensitive detection of the effects of procoagulants and anticoagulants on thrombin generation by using TF in the picomolar range for plasma activation, Baier et al [9] reported that higher concentrations of heparin are required to inhibit thrombin generation in cord plasma than in adult plasma. Several studies on age-dependency of heparin effectiveness that have been published recently are in line with our findings, concluding that pediatric dosage recommendations extrapolated from adult trials are not valid [10][11][12][13]. However, as heparin requires AT to exert its anticoagulant effect, the relative deficiency of AT in neonatal plasma might limit the antithrombotic effects of heparin in this age group.…”

Antithrombotic Therapy in Neonates and Children

“…However, the predictability of the anticoagulant effect with weight-adjusted doses appears to be reduced compared with adults, 101 presumably because of altered plasma binding. 29,102 Throughout the guidelines in this article, we use the term LMWH and present dosing schedules for a num ber of different LMWHs. However, most clinical data with respect to LMWH use in pediatric patients are derived from studies that used enoxaparin.…”

“…4,25,26 Third, the distribution, binding, and clearance of antithrombotic drugs are age dependent. [27][28][29] Fourth, the frequency and type of intercurrent illnesses and concurrent medications vary with age. Fifth, the need for general anesthesia to perform many diagnostic studies in pediatric patients has an impact on the ability to investigate and monitor TEs and, hence, the confi dence one can have in therapeutic decisions.…”