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A Guide to the Use of Anticoagulant Drugs in Children

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Abstract

Increasing thrombotic complications in children with complex medication conditions have led to more widespread use of anticoagulants [Raffini et al. in Pediatrics 124(4):1001–8, 2009]. While current guidelines for the management of antithrombotic therapy in neonates and children exist, they are based on low- and very low-quality evidence [Monagle et al. in Chest 141(2 Suppl):e737–801S, 2012]. Despite numerous differences, current anticoagulation practice is largely extrapolated from adult studies. This is sub-optimal, particularly in neonates who have a rapidly evolving hemostatic system. The majority of pediatric patients have underlying medical conditions that may significantly influence drug choice and bleeding risk. This article reviews the use of anticoagulants in children with thrombosis, focusing on practical aspects such as dosing, monitoring, and complications. Low molecular weight heparin has become the preferred anticoagulant in children, although unfractionated heparin and warfarin remain frequently used. Other anticoagulants, including fondaparinux, direct thrombin inhibitors, and the newer target-specific oral anticoagulants are also discussed. Given the many unique challenges surrounding the use of anticoagulants in children, pediatric hospitals should have written practice guidelines as well as experienced providers to care for children with thrombosis. This is an evolving field, and further studies of the use of anticoagulants in neonates and children are greatly needed to help optimize care.

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References

  1. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children’s hospitals in the United States from 2001 to 2007. Pediatrics. 2009;124(4):1001–8. doi:10.1542/peds.2009-0768.

    Article  PubMed  Google Scholar 

  2. Monagle P, Chan AK, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Gottl U, et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e737S–801S. doi:10.1378/chest.11-2308.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Andrew M, David M, Adams M, Ali K, Anderson R, Barnard D, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994;83(5):1251–7.

    CAS  PubMed  Google Scholar 

  4. Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the full-term infant. Blood. 1987;70(1):165–72.

    CAS  PubMed  Google Scholar 

  5. Ignjatovic V, Furmedge J, Newall F, Chan A, Berry L, Fong C, et al. Age-related differences in heparin response. Thromb Res. 2006;118(6):741–5. doi:10.1016/j.thromres.2005.11.004.

    Article  CAS  PubMed  Google Scholar 

  6. In: The joint commission national patient safety goals. http://www.jointcommission.org/standards_information/jcfaqdetails.aspx?StandardsFaqId=183&ProgramId=47. Accessed 16 Feb 2015.

  7. Yee DL, O’Brien SH, Young G. Pharmacokinetics and pharmacodynamics of anticoagulants in paediatric patients. Clin Pharmacokinet. 2013;52(11):967–80. doi:10.1007/s40262-013-0094-1.

    Article  CAS  PubMed  Google Scholar 

  8. McDonald MM, Jacobson LJ, Hay WW Jr, Hathaway WE. Heparin clearance in the newborn. Pediatr Res. 1981;15(7):1015–8. doi:10.1203/00006450-198107000-00007.

    Article  CAS  PubMed  Google Scholar 

  9. Andrew M, Marzinotto V, Massicotte P, Blanchette V, Ginsberg J, Brill-Edwards P, et al. Heparin therapy in pediatric patients: a prospective cohort study. Pediatr Res. 1994;35(1):78–83. doi:10.1203/00006450-199401000-00016.

    Article  CAS  PubMed  Google Scholar 

  10. Estes JW. Clinical pharmacokinetics of heparin. Clin Pharmacokinet. 1980;5(3):204–20.

    Article  CAS  PubMed  Google Scholar 

  11. Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med. 1972;287(7):324–7. doi:10.1056/NEJM197208172870703.

    Article  CAS  PubMed  Google Scholar 

  12. Schechter T, Finkelstein Y, Ali M, Kahr WH, Williams S, Chan AK, et al. Unfractionated heparin dosing in young infants: clinical outcomes in a cohort monitored with anti-factor Xa levels. J Thromb Haemost. 2012;10(3):368–74. doi:10.1111/j.1538-7836.2012.04624.x.

    Article  CAS  PubMed  Google Scholar 

  13. Vandiver JW, Vondracek TG. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy. 2012;32(6):546–58. doi:10.1002/j.1875-9114.2011.01049.x.

    Article  CAS  PubMed  Google Scholar 

  14. Sackler JP, Liu L. Heparin-induced osteoporosis. Br J Radiol. 1973;46(547):548–50.

    Article  CAS  PubMed  Google Scholar 

  15. Murphy MS, John PR, Mayer AD, Buckels JA, Kelly DA. Heparin therapy and bone fractures. Lancet. 1992;340(8827):1098.

    Article  CAS  PubMed  Google Scholar 

  16. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332(20):1330–5. doi:10.1056/NEJM199505183322003.

    Article  CAS  PubMed  Google Scholar 

  17. Klenner AF, Lubenow N, Raschke R, Greinacher A. Heparin-induced thrombocytopenia in children: 12 new cases and review of the literature. Thromb Haemost. 2004;91(4):719–24. doi:10.1267/THRO04040719.

    CAS  PubMed  Google Scholar 

  18. Newall F, Barnes C, Ignjatovic V, Monagle P. Heparin-induced thrombocytopenia in children. J Paediatr Child Health. 2003;39(4):289–92. doi:10.1046/j.1440-1754.2003.00139.x.

  19. Risch L, Huber AR, Schmugge M. Diagnosis and treatment of heparin-induced thrombocytopenia in neonates and children. Thromb Res. 2006;118(1):123–35. doi:10.1016/j.thromres.2004.12.020.

    Article  CAS  PubMed  Google Scholar 

  20. O’Brien SH, Kulkarni R, Wallace A, Hamblin F, Burr S, Goldenberg NA. Multicenter dose-finding and efficacy and safety outcomes in neonates and children treated with dalteparin for acute venous thromboembolism. J Thromb Haemost. 2014;12(11):1822–5. doi:10.1111/jth.12716.

    Article  PubMed  Google Scholar 

  21. van Ommen CH, van den Dool EJ, Peters M. Nadroparin therapy in pediatric patients with venous thromboembolic disease. J Pediatr Hematol Oncol. 2008;30(3):230–4. doi:10.1097/MPH.0b013e31816356f8.

    Article  PubMed  Google Scholar 

  22. Malowany JI, Knoppert DC, Chan AK, Pepelassis D, Lee DS. Enoxaparin use in the neonatal intensive care unit: experience over 8 years. Pharmacotherapy. 2007;27(9):1263–71. doi:10.1592/phco.27.9.1263.

    Article  CAS  PubMed  Google Scholar 

  23. Bauman ME, Belletrutti MJ, Bajzar L, Black KL, Kuhle S, Bauman ML et al. Evaluation of enoxaparin dosing requirements in infants and children. Better dosing to achieve therapeutic levels. Thromb Haemost. 2009;101(1):86–92. doi:09010086.

  24. Bauman ME, Black KL, Bauman ML, Belletrutti M, Bajzar L, Massicotte MP. Novel uses of insulin syringes to reduce dosing errors: a retrospective chart review of enoxaparin whole milligram dosing. Thromb Res. 2009;123(6):845–7. doi:10.1016/j.thromres.2008.09.001.

    Article  CAS  PubMed  Google Scholar 

  25. O’Brien SH, Lee H, Ritchey AK. Once-daily enoxaparin in pediatric thromboembolism: a dose finding and pharmacodynamics/pharmacokinetics study. J Thromb Haemost. 2007;5(9):1985–7. doi:10.1111/j.1538-7836.2007.02624.x.

    Article  PubMed  Google Scholar 

  26. Trame MN, Mitchell L, Krumpel A, Male C, Hempel G, Nowak-Gottl U. Population pharmacokinetics of enoxaparin in infants, children and adolescents during secondary thromboembolic prophylaxis: a cohort study. J Thromb Haemost. 2010;8(9):1950–8. doi:10.1111/j.1538-7836.2010.03964.x.

    Article  CAS  PubMed  Google Scholar 

  27. Duncan SM, Massicotte MP, Ray L, Kuhle S, Bauman ME. Topical lidocaine and the effect on enoxaparin absorption in children: a pilot study. Thromb Res. 2010;125(1):e1–4. doi:10.1016/j.thromres.2009.08.003.

    Article  CAS  PubMed  Google Scholar 

  28. Young G, Yee DL, O’Brien SH, Khanna R, Barbour A, Nugent DJ. FondaKIDS: a prospective pharmacokinetic and safety study of fondaparinux in children between 1 and 18 years of age. Pediatr Blood Cancer. 2011;57(6):1049–54. doi:10.1002/pbc.23011.

    Article  PubMed  Google Scholar 

  29. Ko RH, Michieli C, Lira JL, Young G. FondaKIDS II: long-term follow-up data of children receiving fondaparinux for treatment of venous thromboembolic events. Thromb Res. 2014;134(3):643–7. doi:10.1016/j.thromres.2014.07.026.

    Article  CAS  PubMed  Google Scholar 

  30. Streif W, Andrew M, Marzinotto V, Massicotte P, Chan AK, Julian JA, et al. Analysis of warfarin therapy in pediatric patients: a prospective cohort study of 319 patients. Blood. 1999;94(9):3007–14.

    CAS  PubMed  Google Scholar 

  31. Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e152S–84S. doi:10.1378/chest.11-2295.

    PubMed Central  CAS  PubMed  Google Scholar 

  32. Rayapudi S, Torres A Jr, Deshpande GG, Ross MP, Wohrley JD, Young G, et al. Bivalirudin for anticoagulation in children. Pediatr Blood Cancer. 2008;51(6):798–801. doi:10.1002/pbc.21731.

    Article  PubMed  Google Scholar 

  33. Young G, Tarantino MD, Wohrley J, Weber LC, Belvedere M, Nugent DJ. Pilot dose-finding and safety study of bivalirudin in infants <6 months of age with thrombosis. J Thromb Haemost. 2007;5(8):1654–9. doi:10.1111/j.1538-7836.2007.02623.x.

    Article  CAS  PubMed  Google Scholar 

  34. Nagle EL, Dager WE, Duby JJ, Roberts AJ, Kenny LE, Murthy MS, et al. Bivalirudin in pediatric patients maintained on extracorporeal life support. Pediatr Crit Care Med. 2013;14(4):e182–8. doi:10.1097/PCC.0b013e31827200b6.

    Article  PubMed  Google Scholar 

  35. Young G, Boshkov LK, Sullivan JE, Raffini LJ, Cox DS, Boyle DA, et al. Argatroban therapy in pediatric patients requiring nonheparin anticoagulation: an open-label, safety, efficacy, and pharmacokinetic study. Pediatr Blood Cancer. 2011;56(7):1103–9. doi:10.1002/pbc.22852.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

No external funding was used in the preparation of this review. L. R. has served as a consultant to GlaxoSmithKline and Eisai. C. L. has no disclosures.

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Authors and Affiliations

  1. Clinical Pharmacy, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Connie Law

  2. Division of Hematology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Colket Translational Research Building-Rm. 11022, 3501 Civic Center Blvd, Philadelphia, PA, 19104, USA

    Leslie Raffini

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Correspondence to Leslie Raffini.

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Law, C., Raffini, L. A Guide to the Use of Anticoagulant Drugs in Children. Pediatr Drugs 17, 105–114 (2015). https://doi.org/10.1007/s40272-015-0120-x

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