Key result
In vitro, rivaroxaban caused a dose-dependent and significantly greater increase in PT, aPTT, and lag time in neonatal plasma compared with adult plasma.
Why the study?
Does rivaroxaban exhibit age-related differences in its in vitro pharmacodynamic anticoagulant effects between neonatal and adult plasma?
Does rivaroxaban exhibit age-related differences in its in vitro pharmacodynamic anticoagulant effects between neonatal and adult plasma?
Rivaroxaban exerts a significantly more pronounced anticoagulant effect in neonatal plasma compared to adult plasma in vitro, highlighting the need for age-specific dosing studies.
Suggests greater neonatal anticoagulant sensitivity in vitro; leaves open age-specific dosing needs pending clinical validation.
The use of anticoagulants in neonates is increasing because of the medical advances improving the long-term survival of very sick infants who are at risk of venous thromboembolism (VTE). Current anticoagulation therapy in neonates is less than ideal, because of the physiological differences compared to children and adults regarding the pathophysiology of thrombosis and pharmacology of the drug. Limitations associated with conventional anticoagulants have prompted the development of novel drugs that specifically target the key proteins in the coagulation system. Rivaroxaban is the first oral, direct Factor Xa inhibitor available for the prevention of VTE in adults. Its predictable pharmacokinetic profile, high oral bioavailability and once-daily dosing make rivaroxaban an optimal anticoagulant that warrants investigation in neonates. This study was designed to determine whether there are age-related differences in the pharmacodynamic effects of rivaroxaban in vitro amongst neonates. Neonatal and adult plasma pools were created and spiked with increasing concentrations of rivaroxaban (0-500 ng/ml). Commercially available prothrombin time (PT), activated partial thromboplastin time (aPTT) and anti-Factor Xa assays as well as a sub-sampling thrombin generation assay were used to measure the rivaroxaban effect. A dose-dependent response was observed for PT, aPTT and lag time in both the age groups. Rivaroxaban caused a significant increase in the clotting time for PT and aPTT as well as an increase in lag time (as measured by thrombin generation) in neonates when compared with adults. In-vivo studies are required to confirm the consistency of dose-response in neonates.
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Attard et al. (2014) studied this question. Rivaroxaban vs. Adult plasma pools was evaluated on Pharmacodynamic effects measured by PT, aPTT, anti-Factor Xa assays, and thrombin generation assay (lag time). In vitro, rivaroxaban caused a dose-dependent and significantly greater increase in PT, aPTT, and lag time in neonatal plasma compared with adult plasma.
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