Asundexian'nin Neonatalarda, Çocuklarda ve Yetişkinlerde İn Vitro Pıhtılaşma Üzerindeki Yaşa Bağlı Etkileri

Özet (abstract)

Understanding age-specific responses to anticoagulants is crucial in the development of safe and effective therapies in children. While direct oral anticoagulants offer many advantages, their bleeding risks remain similar to traditional anticoagulants. Asundexian, a small molecule FXIa inhibitor, has previously demonstrated the potential for minimizing thrombotic complications with minimal bleeding risks in adults and warrants further investigation in children. This study aimed to investigate the in vitro age-related anticoagulant effect of asundexian in healthy neonates and children as compared with adults, prior to in vivo testing. Citrated plasma samples from 60 healthy participants from each of six age groups (neonates, 28 days–1 year, 1–5 years, 6–10 years, 11–16 years, and adults) were pooled and spiked with increasing concentrations of asundexian (0, 0.2983, 1.175, 2.35, 4.7, and 9.4 μM). Across all age groups, a prolonged clotting time was observed in a concentration-dependent response to asundexian when using silica- and kaolin-based activated partial thromboplastin time assays. Both FXI coagulation and FXIa activity decreased with increasing concentrations of asundexian. In vitro findings indicate a concentration-response to asundexian, with significant pharmacodynamic differences in older children at higher concentrations. In vivo studies are required to confirm these findings, optimize dosing, and assess clinical implications in the pediatric population.

Yazarların özeti; kaynağından alınmıştır. Thrombosis and Haemostasis, 2026 · DOI ↗