Thrombosis research · 2025
The in vitro anticoagulant effect of milvexian in healthy neonates and children.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Letunica Natasha, Karlaftis Vasiliki, Monagle Paul, Patino Hernando, Chintala Madhu, Attard Chantal
Аннотация
BACKGROUND: Effective anticoagulant therapies are crucial for managing thrombotic disorders, especially in children. While currently available direct oral anticoagulants offer many advantages over current standard of care anticoagulants, including predictable pharmacokinetics and reduced need for monitoring, they still have significant bleeding risks. Milvexian, a direct factor XIa inhibitor, has demonstrated potential in reducing bleeding risks compared to traditional anticoagulants and warrants further investigation in neonates and children.
OBJECTIVES: This study aimed to investigate the age-related anticoagulant effect of milvexian in vitro.
PATIENTS/METHODS: Plasma samples from healthy participants from the following age groups: neonates, 28 days-23 months, 2-6 years, 7-11 years, 12-18 years, and adults were spiked with increasing concentrations of milvexian (0.1, 1.0, 3.0 and 10 μM). Clotting time was measured using an activated partial thromboplastin time (aPTT) assay, and thrombin generation parameters were assessed.
RESULTS: A dose-dependent increase in clotting time was observed across all age groups. Thrombin generation parameters, including Lag time and time to peak (ttPeak), showed a linear dose-dependent increase, while endogenous thrombin potential (ETP), Peak, and Velocity index decreased dose-dependently. Significant age-specific differences were noted primarily in neonates and children less than two years of age compared to adults.
CONCLUSION: In vitro findings indicate a predictable, linear dose-response to milvexian, with significant in vitro anticoagulant effect differences in neonates and children under two years of age. Further in vivo studies are required to confirm these findings, determine dosing strategies, and assess clinical implications in the paediatric population.
OBJECTIVES: This study aimed to investigate the age-related anticoagulant effect of milvexian in vitro.
PATIENTS/METHODS: Plasma samples from healthy participants from the following age groups: neonates, 28 days-23 months, 2-6 years, 7-11 years, 12-18 years, and adults were spiked with increasing concentrations of milvexian (0.1, 1.0, 3.0 and 10 μM). Clotting time was measured using an activated partial thromboplastin time (aPTT) assay, and thrombin generation parameters were assessed.
RESULTS: A dose-dependent increase in clotting time was observed across all age groups. Thrombin generation parameters, including Lag time and time to peak (ttPeak), showed a linear dose-dependent increase, while endogenous thrombin potential (ETP), Peak, and Velocity index decreased dose-dependently. Significant age-specific differences were noted primarily in neonates and children less than two years of age compared to adults.
CONCLUSION: In vitro findings indicate a predictable, linear dose-response to milvexian, with significant in vitro anticoagulant effect differences in neonates and children under two years of age. Further in vivo studies are required to confirm these findings, determine dosing strategies, and assess clinical implications in the paediatric population.