Key result
Dabigatran etexilate concentration-clotting time relationships were largely comparable between children and adults, with a slight upward shift in ECT and aPTT in children aged <2 months.
Why the study?
Does the relationship between plasma dabigatran concentration and coagulation assay results differ in pediatric patients compared with adults?
Does the relationship between plasma dabigatran concentration and coagulation assay results differ in pediatric patients compared with adults?
Developmental hemostatic changes have little impact on the coagulation assay response to dabigatran in children compared to adults, except for a slight shift in infants under 2 months of age.
Assay responses to dabigatran are largely similar across pediatric ages and adults; extends adult PK/PD data but leaves clinical adoption open pending trials.
BACKGROUND: Physiological age-related changes in the haemostatic and coagulation systems result in differing anticoagulant assay responses to standard anticoagulants. Therefore, we investigated the response of anticoagulant assays to dabigatran etexilate (DE) in children compared with adults. OBJECTIVE: This article assesses the relationship between plasma dabigatran concentration and coagulation assay results across age groups in children and adults. PATIENTS AND METHODS: Data from three clinical trials in which children received DE following standard of care for venous thromboembolism were compared with data from adult clinical trials. The effects of dabigatran concentration on diluted thrombin time (dTT), ecarin clotting time (ECT) and activated partial thromboplastin time (aPTT) were analysed graphically and with modelling. RESULTS: The concentration-dTT relationships were consistent in children across all ages and adults in the graphical analysis. For ECT and aPTT, relationships based on ratios over baseline were similar across all ages; absolute clotting times showed that the same exposure resulted in longer clotting times in some of the children aged < 1 year versus adults. Modelling showed concentration-clotting time relationships for all three assays were largely comparable between adults and children, except in those aged < 2 months, in whom there was a slight upward shift in ECT and aPTT relative to adults. CONCLUSION: Results suggest that developmental haemostatic changes will have little impact on response to DE. However, further paediatric clinical trials assessing the relationship between coagulation assay responses and clinical outcomes will be needed to confirm this finding.
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Maas et al. (2018) studied Venous thromboembolism. Dabigatran etexilate vs. Adults was evaluated on Relationship between plasma dabigatran concentration and coagulation assay results (dTT, ECT, aPTT). Dabigatran etexilate concentration-clotting time relationships were largely comparable between children and adults, with a slight upward shift in ECT and aPTT in children aged <2 months.
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