Effectiveness and Safety of Nadroparin Therapy in Preterm and Term Neonates with Venous Thromboembolism

Abstract

Introduction: Optimal neonatal nadroparin dosages to treat venous thromboembolism (VTE) are unknown. Objective: To evaluate therapeutic nadroparin dosages to reach therapeutic target ranges (TTR: 0.5–1.0 International Unit (IU)/mL) and the effectiveness and safety of nadroparin in neonatal VTE. Methods: Retrospective study including neonates with VTE on nadroparin in a tertiary center between 2007 and 2018. Two groups were distinguished: neonates before (group 1) and after (group 2) switch to higher starting dosages in 2014. Results: Sixty-one neonates (44 preterm, 17 term) with 64 VTEs were included. TTR was reached in 32/64 (50%) VTEs (group 1: 35.7%; group 2: 61.1%). Median nadroparin dosage to reach TTR was 197 (97.9–330.3) IU/kg/12 h. No therapy-related deaths occurred. Recurrent VTE developed in 6 (9.8%) neonates. Complete clot resolution was observed in 31/41 (75.6%) VTEs. TTR was reached in 58.1% VTEs with complete clot resolution. No major bleeding occurred. Non-major clinically relevant bleedings occurred in 3/64 (4.7%) VTEs, consisting of large hematomas due to the use of subcutaneous catheters. Conclusions: High nadroparin dosages are needed to reach TTR in neonates, which seem to be safe. Clot resolution may occur without reaching TTR. Subcutaneous catheters may cause important bleeding complications.

Is the current therapeutic dosage of nadroparin adequate for neonates and infants under 8 months with thromboembolic disease? a population pharmacokinetic study from a national children’s medical center

“…Van Ommen's et al conducted a prospective study involving two preterm and ten term neonates treated with nadroparin therapy at an initial dosage of 85.5 IU/kg q12 h, eventually six of them (50%) achieved TTR between 0.5 and 1.0 IU/mL with a mean dosage of 224 ± 21 IU/kg q12 h but required significantly more time compared to older children (Ommen et al, 2008). Jeanine Sol et al investigated sixty-one preterm and term neonates with 64 venous thromboembolisms, where fifty percent (32/64) reached TTR and the median nadroparin dosage required to reach TTR was found to be 197 (97.9-330.3) IU/kg q12 h (Sol et al, 2021). This study is subject to certain constraints.…”