Balancing safety and efficacy of low-molecular-weight heparins in neonates: a systematic review

Abstract

The rising incidence of venous thromboembolism (VTE) in neonates has led to increased use of low-molecular-weight heparins (LMWHs), but optimal dosages remain uncertain. A serious adverse effect of LMWHs is major bleeding. Given the vulnerability of neonates to major bleeding, we aimed to review therapeutic and prophylactic LMWH dosages to achieve target anti-factor Xa ranges of 0.5 and 1.0 U/mL and 0.1 and 0.4 U/mL, respectively. Our secondary aim was to assess the safety and efficacy of LMWHs in neonates. A systematic review of all published studies between 1996 and 2023 that pertained to the dosing, safety, or efficacy of LMWH in preterm and term neonates. Studies were identified through the Medline database. Data on LMWH dosages, bleeding events, resolution and recurrence, and anti-factor Xa levels were analyzed. A total of 38 studies involving 1145 neonates were included. To achieve a therapeutic or prophylactic target range, weight-adjusted initial dosages of LMWH had to be increased by 21% particularly in premature neonates. During therapeutic therapy, major bleeding occurred in 4.1% and minor bleeding in 7.1%. During prophylactic therapy, 11.4% experienced major bleeding and 17.1% minor bleeding. With therapeutic dosages, 55.8% achieved complete VTE resolution. Additionally, 68.5% of neonates initially failed to achieve therapeutic anti-factor Xa levels, persisting in 29.4% despite dose adjustments. A higher initial therapeutic dosage of LMWHs may be needed in neonates. In addition, the patient’s gestational age must be considered in the dosing strategy to optimize outcomes. Although this must be weighed against bleeding risk at an individual level.