Anticoagulation therapy in neonates, children and adolescents

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Abstract

Anticoagulation of neonates, children and adolescents remains an important part of clinical care for many individuals. There are different options for anticoagulation, each with their own advantages and disadvantages and selection of an appropriate anticoagulation regime for the specific condition should be judicious. This is in part because age related differences in the coagulation systems exist that mean that the pharmacokinetics and pharmacodynamics of anticoagulation drugs vary across the pediatric spectrum in addition to being distinct from adults. The use of anticoagulant drugs presents specific challenges in the pediatric setting. This review will consider the main anticoagulants currently in use in neonates, children and adolescents, specifically Heparin (unfractionated heparin and low molecular weight heparin) vitamin K antagonist (warfarin) as well as a brief discussion of fondaparinux.

Introduction

Anticoagulation in neonates, children and adolescents is an important clinical area in light of the increasing incidence of thrombosis, and therefore potential complications arising from thrombosis in the pediatric setting [1]. Thrombosis in paediatrics is a rare, but serious event with an estimated incidence of 58 per 10,000 hospital admissions and clinical management remains challenging [1], [2]. Predisposing factors for the development of thrombosis include the presence of vascular access devices, congenital cardiac disease, cancer, renal disease, organ transplantation, infection, inflammation and prematurity [3]. Anticoagulants are administered for the treatment of thrombosis to assist resolution, decrease the risk of embolism, limit extension and prevent recurrence or for thrombosis prophylaxis in individuals at risk [4].

The American College of Chest Physicians (ACCP) regularly publish recommendations based on the available evidence to guide clinical practice of Antithrombotic therapy in neonates and children, for specific clinical situations and scenarios [5], [6], [7], [8], [9], [10]. Despite much research in the field, many of the recommendations are based on low-grade evidence because high quality safety and efficacy studies are hard to conduct in the pediatric setting and thus many of the recommendations are extrapolated from adult studies. The lack of data specific to paediatrics complicates evidence-based management of anticoagulant therapy.

This is in part because neonates, children and adolescents are unique in their physiology, clinical conditions and response to pharmacologic agents. Developmental haemostasis is a term used to describe the physiological age related changes in the coagulation system [11], [12]. Dynamic changes of the hematologic system are evident throughout childhood, in the premature infant through to adolescents rendering anticoagulation management of different age ranges complex. Pediatric anticoagulation is a specialised area and as such, the ACCP recommended that a paediatric haematologist is required to manage anticoagulation therapy or alternatively, a neonatologist or pediatrician in collaboration with an experienced adult haematologist [9].

There is a range of anticoagulant agents available for the treatment of thrombosis in paediatrics with heparin, LMWH and warfarin being the most commonly used in paediatrics [13]. These agents are compared in Table 1. Choice of anticoagulant depends on considerations such as the presenting condition, risk of adverse events, drug interactions, diet, compliance, duration of therapy and patient and family preference. This review aims to provide an overview of the anticoagulation agents currently used in the pediatric setting. This will include description of the mechanisms of action, therapeutic ranges, dosing regimens, monitoring requirements and adverse effects.

Section snippets

Unfractionated heparin

Unfractionated heparin is a heavily sulphated mucopolysaccharide. Heparin molecules range in molecular weight from 3000 to 30,000 kDa (mean 15,000), but only a third of the molecules have the pentasaccharide sequence required for the anticoagulant activity of UFH.

Conclusion

Pediatric anticoagulation is a very unique area where extrapolation from adult studies is suboptimal. The most commonly used anticoagulant drugs in use have some data specific to the pediatric setting, and newer agents are being studied in a more systematic manner. However, there are many more studies required on anticoagulation in paediatrics, as the majority of the recommendations currently in use are based on low levels of evidence [9]. Studies examining monitoring regimens, drug target

Funding sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of interest

Nil.

Contributors

MH, PM and AC wrote and reviewed the article. All authors have approved the final article.

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