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

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 the...

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Main Authors: Marieke Verweij, Mirjam M. van Weissenbruch, Irene L.M. Klaassen
Format: Article
Language:English
Published: Elsevier 2024-10-01
Series:Research and Practice in Thrombosis and Haemostasis
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Online Access:http://www.sciencedirect.com/science/article/pii/S2475037924002966
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author Marieke Verweij
Mirjam M. van Weissenbruch
Irene L.M. Klaassen
author_facet Marieke Verweij
Mirjam M. van Weissenbruch
Irene L.M. Klaassen
author_sort Marieke Verweij
collection DOAJ
description 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.
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spelling doaj-art-9295dba84ed747ac8fea75c4afa9dff92024-11-23T06:31:27ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792024-10-0187102601Balancing safety and efficacy of low-molecular-weight heparins in neonates: a systematic reviewMarieke Verweij0Mirjam M. van Weissenbruch1Irene L.M. Klaassen2Department of Pediatrics—Hematology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the NetherlandsDepartment of Pediatrics—Neonatology, Emma Children’s Hospital, Amsterdam University Medical Centers, VU University Amsterdam, Amsterdam, the NetherlandsDepartment of Pediatrics—Hematology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Correspondence Irene L.M. Klaassen, Department of Pediatrics—Hematology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.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.http://www.sciencedirect.com/science/article/pii/S2475037924002966efficacylow-molecular-weight heparinneonatessafetyvenous thromboembolic disease
spellingShingle Marieke Verweij
Mirjam M. van Weissenbruch
Irene L.M. Klaassen
Balancing safety and efficacy of low-molecular-weight heparins in neonates: a systematic review
Research and Practice in Thrombosis and Haemostasis
efficacy
low-molecular-weight heparin
neonates
safety
venous thromboembolic disease
title Balancing safety and efficacy of low-molecular-weight heparins in neonates: a systematic review
title_full Balancing safety and efficacy of low-molecular-weight heparins in neonates: a systematic review
title_fullStr Balancing safety and efficacy of low-molecular-weight heparins in neonates: a systematic review
title_full_unstemmed Balancing safety and efficacy of low-molecular-weight heparins in neonates: a systematic review
title_short Balancing safety and efficacy of low-molecular-weight heparins in neonates: a systematic review
title_sort balancing safety and efficacy of low molecular weight heparins in neonates a systematic review
topic efficacy
low-molecular-weight heparin
neonates
safety
venous thromboembolic disease
url http://www.sciencedirect.com/science/article/pii/S2475037924002966
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