Abstract
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.
Keywords
anticoagulants - dabigatran - direct thrombin inhibitor - paediatrics - venous thromboembolism
