Anticoagulant therapy in pediatrics

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Abstract

Thromboembolic episodes are disorders encountered in both children and adults, but relatively more common in adults. However, the occurrence of venous thromboembolism and use of anticoagulants in pediatrics are increasing. Unfractionated Heparin (UH) is used as a treatment and prevention of thrombosis in adults and critically ill children. Heparin utilization in pediatric is limited by many factors and the most important ones are Heparin Induced Thrombocytopenia (HIT) and anaphylaxis. However, Low Molecular Weight Heparin (LMWH) appears to be an effective and safe alternative treatment. Hence, it is preferred over than UH due to favorable pharmacokinetic and side effect profile. Direct Thrombin Inhibitors (DTI) is a promising class over the other anticoagulants since it offers potential advantages. The aim of this review is to discuss the differences between adult and pediatric thromboembolism and to review the current anticoagulants in terms of pharmacological action, doses, drug reactions, pharmacokinetics, interactions, and parameters. This review also highlights the differences between old and new anticoagulant therapy in pediatrics.

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Most cited references 76

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Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007.

C Witmer, Chris Feudtner, Leslie Raffini … (2009)

The goals were to determine whether there has been an increase in the rate of venous thromboembolism (VTE) in pediatric tertiary care hospitals and to evaluate the use of anticoagulants in the treatment of hospitalized pediatric patients with VTE. A retrospective cohort study of patients or =1 coexisting chronic complex medical condition. Pediatric malignancy was the medical comorbid condition associated most strongly with recurrent VTE (P < .001). The proportion of children with VTE who were treated with enoxaparin increased from 29% to 49% during this time period (P < .001); the use of warfarin decreased slightly from 11.4% to 9.6% (P= .02). Increasing age was associated with increased likelihood of patients with VTE being treated with either enoxaparin or warfarin. This multicenter study demonstrates a dramatic increase in the diagnosis of VTE at children's hospitals from 2001 to 2007.

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Contaminated heparin associated with adverse clinical events and activation of the contact system.

Kevin D Pelzer, Ram Sasisekharan, Mark T. Whary … (2008)

There is an urgent need to determine whether oversulfated chondroitin sulfate (OSCS), a compound contaminating heparin supplies worldwide, is the cause of the severe anaphylactoid reactions that have occurred after intravenous heparin administration in the United States and Germany. Heparin procured from the Food and Drug Administration, consisting of suspect lots of heparin associated with the clinical events as well as control lots of heparin, were screened in a blinded fashion both for the presence of OSCS and for any biologic activity that could potentially link the contaminant to the observed clinical adverse events. In vitro assays for the activation of the contact system and the complement cascade were performed. In addition, the ability of OSCS to recapitulate key clinical manifestations in vivo was tested in swine. The OSCS found in contaminated lots of unfractionated heparin, as well as a synthetically generated OSCS reference standard, directly activated the kinin-kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. In addition, OSCS induced generation of C3a and C5a, potent anaphylatoxins derived from complement proteins. Activation of these two pathways was unexpectedly linked and dependent on fluid-phase activation of factor XII. Screening of plasma samples from various species indicated that swine and humans are sensitive to the effects of OSCS in a similar manner. OSCS-containing heparin and synthetically derived OSCS induced hypotension associated with kallikrein activation when administered by intravenous infusion in swine. Our results provide a scientific rationale for a potential biologic link between the presence of OSCS in suspect lots of heparin and the observed clinical adverse events. An assay to assess the amidolytic activity of kallikrein can supplement analytic tests to protect the heparin supply chain by screening for OSCS and other highly sulfated polysaccharide contaminants of heparin that can activate the contact system. Copyright 2008 Massachusetts Medical Society.

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Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

A Lincoff, T Warkentin, Andreas Greinacher … (2008)

This chapter about the recognition, treatment, and prevention of heparin-induced thrombocytopenia (HIT) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices. Among the key recommendations in this chapter are the following: For patients receiving heparin in whom the clinician considers the risk of HIT to be > 1.0%, we recommend platelet count monitoring over no platelet count monitoring (Grade 1C). For patients who are receiving heparin or have received heparin within the previous 2 weeks, we recommend investigating for a diagnosis of HIT if the platelet count falls by >/= 50%, and/or a thrombotic event occurs, between days 5 and 14 (inclusive) following initiation of heparin, even if the patient is no longer receiving heparin therapy when thrombosis or thrombocytopenia has occurred (Grade 1C). For patients with strongly suspected (or confirmed) HIT, whether or not complicated by thrombosis, we recommend use of an alternative, nonheparin anticoagulant (danaparoid [Grade 1B], lepirudin [Grade 1C], argatroban [Grade 1C], fondaparinux [Grade 2C], or bivalirudin [Grade 2C]) over the further use of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) therapy or initiation/continuation of vitamin K antagonists (VKAs) [Grade 1B]. The guidelines include specific recommendations for nonheparin anticoagulant dosing that differ from the package inserts. For patients with strongly suspected or confirmed HIT, we recommend against the use of vitamin K antagonist (VKA) [coumarin] therapy until after the platelet count has substantially recovered (usually, to at least 150 x 10(9)/L) over starting VKA therapy at a lower platelet count (Grade 1B); that VKA therapy be started only with low maintenance doses (maximum, 5 mg of warfarin or 6 mg of phenprocoumon) over higher initial doses (Grade 1B); and that the nonheparin anticoagulant (eg, lepirudin, argatroban, danaparoid) be continued until the platelet count has reached a stable plateau, the international normalized ratio (INR) has reached the intended target range, and after a minimum overlap of at least 5 days between nonheparin anticoagulation and VKA therapy rather than a shorter overlap (Grade 1B). For patients receiving VKAs at the time of diagnosis of HIT, we recommend use of vitamin K (10 mg po or 5 to 10 mg IV) [Grade 1C].

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Journal

Journal ID (nlm-ta): J Basic Clin Pharm

Journal ID (iso-abbrev): J Basic Clin Pharm

Journal ID (publisher-id): JBCP

Title: Journal of Basic and Clinical Pharmacy

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 0976-0105

ISSN (Electronic): 0976-0113

Publication date (Print): March 2014-May 2014

Volume: 5

Issue: 2

Pages: 27-33

Affiliations

[1] Department of Pharmacy Practice, School of Pharmacy, Lebanese International University, Beirut, Lebanon

[1 ] Department of Biomedical Sciences, School of Pharmacy, Lebanese International University, Beirut, Lebanon

[2 ] Department of PharmD, School of Pharmacy, Lebanese International University, Beirut, Lebanon

Author notes

Address for correspondence: Dr. Mariam K. Dabbous, Department of Pharmacy Practice, School of Pharmacy, Lebanese International University, Saleem Salam, Beirut, Lebanon. E-mail: mariam.dabbous@ 123456liu.edu.lb

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Publisher ID: JBCP-5-27

DOI: 10.4103/0976-0105.134947

PMC ID: 4074692

PubMed ID: 25031496

SO-VID: 80130f26-872a-4b98-83fc-b14125129c17

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Anticoagulant therapy in pediatrics

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Most cited references 76

Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007.

Contaminated heparin associated with adverse clinical events and activation of the contact system.

Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

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