Skip to main content

Utility of a Dedicated Pediatric Cardiac Anticoagulation Program: The Boston Children’s Hospital Experience

Abstract

Congenital heart disease is the leading cause of stroke in children. Warfarin therapy can be difficult to manage safely in this population because of its narrow therapeutic index, multiple drug and dietary interactions, small patient size, high-risk cardiac indications, and lack of data to support anticoagulation recommendations. We sought to describe our institution’s effort to develop a dedicated cardiac anticoagulation service to address the special needs of this population and to review the literature. In 2009, in response to Joint Commission National Patient Safety Goals for Anticoagulation, Boston Children’s Hospital created a dedicated pediatric Cardiac Anticoagulation Monitoring Program (CAMP). The primary purpose was to provide centralized management of outpatient anticoagulation to cardiac patients, to serve as a disease-specific resource to families and providers, and to devise strategies to evolve clinical care with rapidly emerging trends in anticoagulation care. Over 5 years the CAMP Service, staffed by a primary pediatric cardiology attending, a full-time nurse practitioner, and administrative assistant with dedicated support from pharmacy and nutrition, has enrolled over 240 patients ranging in age from 5 months to 55 years. The most common indications include a prosthetic valve (34 %), Fontan prophylaxis (20 %), atrial arrhythmias (11 %), cardiomyopathy (10 %), Kawasaki disease (7 %), and a ventricular assist device (2 %). A patient-centered multi-disciplinary cardiac anticoagulation clinic was created in 2012. Overall program international normalized ratio (INR) time in therapeutic range (TTR) is favorable at 67 % (81 % with a 0.2 margin) and has improved steadily over 5 years. Pediatric-specific guidelines for VKOR1 and CYP2C9 pharmacogenomics testing, procedural bridging with enoxaparin, novel anticoagulant use, and quality metrics have been developed. Program satisfaction is rated highly among families and providers. A dedicated pediatric cardiac anticoagulation program offers a safe and effective strategy to standardize anticoagulation care for pediatric cardiology patients, is associated with high patient and provider satisfaction, and is capable of evolving care strategies with emerging trends in anticoagulation.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. Almond CS, Morales DL, Blackstone EH et al (2013) Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children. Circulation 127(16):1702–1711

    Article  CAS  PubMed  Google Scholar 

  2. Bauman M. Email to CS Almond regarding Methodology for calculating the Percent Time within Therapeutic Range used in the Edmonton KidClot Program, 30 Dec 2013

  3. Bauman ME, Black K, Kuhle S et al (2009) KIDCLOT: the importance of validated educational intervention for optimal long term warfarin management in children. Thromb Res 123(5):707–709

    Article  CAS  PubMed  Google Scholar 

  4. Birnie DH, Healey JS, Wells GA et al (2013) Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med 368(22):2084–2093

    Article  CAS  PubMed  Google Scholar 

  5. Blume ED, Naftel DC, Bastardi HJ et al (2006) Outcomes of children bridged to heart transplantation with ventricular assist devices: a multi-institutional study. Circulation 113(19):2313–2319

    Article  PubMed  Google Scholar 

  6. Bonow RO, Carabello BA, Chatterjee K et al (2008) Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 118(15):e523–e661

    Article  PubMed  Google Scholar 

  7. Cabrera AG, Sundareswaran KS, Samayoa AX et al (2013) Outcomes of pediatric patients supported by the HeartMate II left ventricular assist device in the United States. J Heart Lung Transplant 32(11):1107–1113

    Article  PubMed  Google Scholar 

  8. Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361(12):1139–1151

    Article  CAS  PubMed  Google Scholar 

  9. Cove CL, Hylek EM (2013) An updated review of target-specific oral anticoagulants used in stroke prevention in atrial fibrillation, venous thromboembolic disease, and acute coronary syndromes. J Am Heart Assoc 2(5):e000136

    Article  PubMed Central  PubMed  Google Scholar 

  10. Douketis JD, Johnson JA, Turpie AG (2004) Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med 164(12):1319–1326

    Article  CAS  PubMed  Google Scholar 

  11. Douketis JD, Spyropoulos AC, Spencer FA et al (2012) Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl):e326S–e350S

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Dowling MM, Hynan LS, Lo W et al (2013) International paediatric stroke study: stroke associated with cardiac disorders. Int J Stroke 8(Suppl A100):39–44

    Article  PubMed  Google Scholar 

  13. Eijgenraam P, Ten Cate H, Ten Cate-Hoek A (2013) Safety and efficacy of bridging with low molecular weight heparins: a systematic review and partial meta-analysis. Curr Pharm Des 19(22):4014–4023

    Article  CAS  PubMed  Google Scholar 

  14. Fanikos J, Tsilimingras K, Kucher N, Rosen AB, Hieblinger MD, Goldhaber SZ (2004) Comparison of efficacy, safety, and cost of low-molecular-weight heparin with continuous-infusion unfractionated heparin for initiation of anticoagulation after mechanical prosthetic valve implantation. Am J Cardiol 93(2):247–250

    Article  CAS  PubMed  Google Scholar 

  15. Fraser CD Jr, Jaquiss RD, Rosenthal DN et al (2012) Prospective trial of a pediatric ventricular assist device. N Engl J Med 367(6):532–541

    Article  CAS  PubMed  Google Scholar 

  16. Ghanbari H, Phard WS, Al-Ameri H et al (2012) Meta-analysis of safety and efficacy of uninterrupted warfarin compared to heparin-based bridging therapy during implantation of cardiac rhythm devices. Am J Cardiol 110(10):1482–1488

    Article  CAS  PubMed  Google Scholar 

  17. Giglia TM, Dinardo J, Ghanayem NS et al (2012) Bleeding and thrombotic emergencies in pediatric cardiac intensive care: unchecked balances. World J Pediatr Congenit Heart Surg 3(4):470–491

    Article  PubMed  Google Scholar 

  18. Giglia TM, Massicotte MP, Tweddell JS et al (2013) Prevention and treatment of thrombosis in pediatric and congenital heart disease: a scientific statement from the american heart association. Circulation 128(24):2622–2703

    Article  PubMed  Google Scholar 

  19. Glatz AC, Shah SS, McCarthy AL et al (2013) Prevalence of and risk factors for acute occlusive arterial injury following pediatric cardiac catheterization: a large single-center cohort study. Catheter Cardiovasc Interv 82(3):454–462

    Article  PubMed  Google Scholar 

  20. Goldhaber SZ (2006) “Bridging” and mechanical heart valves: perils, promises, and predictions. Circulation 113(4):470–472

    Article  PubMed  Google Scholar 

  21. Granger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981–992

    Article  CAS  PubMed  Google Scholar 

  22. Hammerstingl C, Tripp C, Schmidt H, von der Recke G, Omran H (2007) Periprocedural bridging therapy with low-molecular-weight heparin in chronically anticoagulated patients with prosthetic mechanical heart valves: experience in 116 patients from the prospective BRAVE registry. J Heart Valve Dis 16(3):285–292

    PubMed  Google Scholar 

  23. Hemostasis and Thrombosis Center. Nationawide Children’s Hospital. http://www.nationwidechildrens.org/hemostasis-and-thrombosis-center. Accessed Feb 24 2014

  24. International Warfarin Pharmacogenetics C, Klein TE, Altman RB et al (2009) Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 360(8):753–764

    Article  Google Scholar 

  25. Khairy P, Fernandes SM, Mayer JE Jr et al (2008) Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation 117(1):85–92

    Article  PubMed  Google Scholar 

  26. Kimmel SE, French B, Kasner SE et al (2013) A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med 369(24):2283–2293

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Lala M, Burckart GJ, Takao CM, Pravica V, Momper JD, Gobburu JV (2013) Genetics-based pediatric warfarin dosage regimen derived using pharmacometric bridging. J Pediatr Pharmacol Ther: JPPT 18(3):209–219

    PubMed Central  PubMed  Google Scholar 

  28. McCrindle BW, Li JS, Manlhiot C et al (2014) Challenges and priorities for research: a report from the NHLBI/NIH Working Group on Thrombosis in Pediatric Cardiology and Congenital Heart Disease. Circulation 130:1192–1203

    Article  PubMed  Google Scholar 

  29. Meurin P, Tabet JY, Weber H, Renaud N, Ben Driss A (2006) Low-molecular-weight heparin as a bridging anticoagulant early after mechanical heart valve replacement. Circulation 113(4):564–569

    Article  CAS  PubMed  Google Scholar 

  30. Monagle P, Chan AK, Goldenberg NA et al (2012) 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 141(2 Suppl):e737S–e801S

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. National patient safety goal (03.05.01) for anticoagulation. http://www.jointcommission.org/assets/1/6/HAP_NPSG_Chapter_2014.pdf. Accessed Feb 24 2014

  32. Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883–891

    Article  CAS  PubMed  Google Scholar 

  33. Percent time in therapeutic INR range (TTR): mean TTR achieved among patients who received prescriptions for warfarin and had sufficient INR values to calculate TTR. National Quality Measures Clearinghouse (NQMC). Agency for Healthcare Research and Quality (AHRQ). http://www.qualitymeasures.ahrq.gov/content.aspx?id=32739. Accessed Feb 24 2014

  34. Pirmohamed M, Burnside G, Eriksson N et al (2013) A randomized trial of genotype-guided dosing of warfarin. N Engl J Med 369(24):2294–2303

    Article  CAS  PubMed  Google Scholar 

  35. Rose AJ, Hylek EM, Ozonoff A, Ash AS, Reisman JI, Berlowitz DR (2011) Risk-adjusted percent time in therapeutic range as a quality indicator for outpatient oral anticoagulation: results of the veterans affairs study to improve anticoagulation (VARIA). Circ Cardiovasc Qual Outcomes 4(1):22–29

    Article  PubMed  Google Scholar 

  36. Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E (1993) A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 69(3):236–239

    CAS  PubMed  Google Scholar 

  37. Ryan F, Byrne S, O’Shea S (2008) Managing oral anticoagulation therapy: improving clinical outcomes. A review. J Clin Pharm Ther 33(6):581–590

    Article  CAS  PubMed  Google Scholar 

  38. Stein ML, Bruno JL, Konopacki KL, Kesler S, Reinhartz O, Rosenthal D (2013) Cognitive outcomes in pediatric heart transplant recipients bridged to transplantation with ventricular assist devices. J Heart Lung Transplant 32(2):212–220

    Article  PubMed  Google Scholar 

  39. Thrombosis and Anticoagulation Program; Boston Children’s Hospital. http://www.childrenshospital.org/centers-and-services/programs/o-_-z/thrombosis-and-anticoagulation-program/overview. Accessed Feb 14 2014

  40. Thrombosis Clinical Program. Texas Children’s Hospital. http://txch.org/hematology-center/hemophilia-thrombosis-center/thrombosis-clinic/. Accessed Feb 24 2014

  41. Thrombosis Program. The Children’s Hospital of Philadelphia. http://www.chop.edu/service/hematology/our-programs/hemostasis-and-thrombosis-center/thrombosis-program.html. Accessed Feb 24 2014

  42. Vahanian A, Alfieri O, Andreotti F et al (2012) Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 33(19):2451–2496

    Article  PubMed  Google Scholar 

  43. Wan Y, Heneghan C, Perera R et al (2008) Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovasc Qual Outcomes 1(2):84–91

    Article  PubMed  Google Scholar 

  44. (2013) Bleeding with dabigatran, rivaroxaban, apixaban. No antidote, and little clinical experience. Prescrire Int 22(139):155–159

  45. Siegal DM, Crowther MA (2013) Acute management of bleeding in patients on novel oral anticoagulants. Eur Heart J 34(7):489–498b

    Article  CAS  PubMed  Google Scholar 

  46. Steiner T, Bohm M, Dichgans M et al (2013) Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban. Clin Res Cardiol 102(6):399–412

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to express their sincerest thanks to Drs. Jane Newburger, Roger Breitbart and James Lock; Michelle Hurtig MSN, RN, Juli-anne Evangelista NP and Karen Hinsley RN, along with all the medical staff from 8E, 8S and the Cardiology Clinic with the Department of Cardiology; and Drs. Ellis Neufeld, Alan Michelson, Cameron Trenor and Juliann Duzan RN of the Division of Hematology, for their enormous support of the CAMP Service over the past 5 years.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christopher S. Almond.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Murray, J.M., Hellinger, A., Dionne, R. et al. Utility of a Dedicated Pediatric Cardiac Anticoagulation Program: The Boston Children’s Hospital Experience. Pediatr Cardiol 36, 842–850 (2015). https://doi.org/10.1007/s00246-014-1089-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-014-1089-x

Keywords

  • Congential heart disease (CHD)
  • Anticoagulation
  • Time in therapeutic range (TTR)
  • International normalized ratio (INR)
  • Cerebrovascular accident
  • Thrombosis