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Semin Thromb Hemost 2019; 45(01): 073-085
DOI: 10.1055/s-0038-1676375
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Antiplatelet Therapy Monitoring in Neonates and Children

Joanna Yilin Huang
1   School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
2   Hematology Research Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia
3   Department of Clinical Hematology, Royal Children's Hospital, Parkville, Victoria, Australia
,
Diajeng Ayesha Soeharto
4   Faculty of Medicine, Dentistry, and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia
5   Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
,
Ivan Damara
4   Faculty of Medicine, Dentistry, and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia
5   Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
,
Vera Ignjatovic
2   Hematology Research Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia
6   Department of Pediatrics, The University of Melbourne, Parkville, Victoria, Australia
,
Matthew D. Linden
7   School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia
,
Paul Monagle
2   Hematology Research Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia
3   Department of Clinical Hematology, Royal Children's Hospital, Parkville, Victoria, Australia
6   Department of Pediatrics, The University of Melbourne, Parkville, Victoria, Australia
› Author Affiliations Funding Nil.
Further Information

Publication History

Publication Date:
19 December 2018 (online)

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Abstract

Antiplatelet agents are used for the prevention and treatment of thromboembolic disease in an increasingly complex population of pediatric patients. Despite their importance for clinical outcome, there is no consensus on the most effective monitoring strategies. This review describes the current state of knowledge focusing on antiplatelet therapy monitoring in children. The authors searched five databases (PubMed-NCBI, MEDLINE-OVID, SCOPUS-Elsevier, ScienceDirect, and Cochrane) from January 2000 to October 2017 using keywords selected a priori. Identified articles were sorted according to the antiplatelet agents administered, methods of antiplatelet monitoring, and outcome measures. Twenty studies were included, with 14 cohort studies, 3 randomized controlled trials, and 3 cross-sectional studies. Eleven different antiplatelet monitoring tools were used, with the most common being Light Transmission Aggregometry, Urinary Thromboxane, Thromboelastography with Platelet Mapping, and VerifyNow. In the majority of studies, antiplatelet therapy monitoring was used to describe adequacy or responsiveness to treatment based on laboratory cut-off values, which were not uniform and sourced from adult studies or extrapolated from test manuals. Several studies evaluated monitoring related to clinical outcome or adjusted therapy to reach predefined therapeutic targets. There was no single laboratory method found to be distinctly better for monitoring antiplatelet treatment. Associations between laboratory assays and clinical outcomes or assays and gold standard measurements were highly inconsistent. The current literature lacks consensus on clinical benefits and measurable effects of monitoring antiplatelet therapy in pediatric patients. This review highlights important areas for research required to determine the value of antiplatelet therapy monitoring in children.

Keywords

antiplatelet therapy - monitoring - child - therapy - prevention

Disclosures

All authors report that they have no relationships relevant to the contents of this study to disclose.


 

  • References

  • 1 Monagle P, Chan AKC, Goldenberg NA. , 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-e801S
    CrossrefPubMedGoogle Scholar
  • 2 Snoep JD, Hovens MMC, Eikenboom JCJ, van der Bom JG, Huisman MV. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: a systematic review and meta-analysis. Arch Intern Med 2007; 167 (15) 1593-1599
    CrossrefPubMedGoogle Scholar
  • 3 Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR. Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ 2008; 336 (7637): 195-198
    CrossrefPubMedGoogle Scholar
  • 4 Breet NJ, van Werkum JW, Bouman HJ. , et al. High on-treatment platelet reactivity to both aspirin and clopidogrel is associated with the highest risk of adverse events following percutaneous coronary intervention. Heart 2011; 97 (12) 983-990
    CrossrefPubMedGoogle Scholar
  • 5 Cattaneo M. Resistance to antiplatelet drugs: molecular mechanisms and laboratory detection. J Thromb Haemost 2007; 5 (Suppl 1): 230-237
    CrossrefPubMedGoogle Scholar
  • 6 Wells BSG. , O'Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp . Published 2014 . Accessed July 8, 2018
    PubMed
  • 7 PEDro scale. Available at: https://www.pedro.org.au/wp-content/uploads/PEDro_scale.pdf . Published 1999 . Accessed July 8, 2018
    PubMed
  • 8 University of Bern. Strobe statement. 2009 . Available at: https://www.strobe-statement.org/fileadmin/Strobe/uploads/checklists/STROBE_checklist_v4_combined.pdf . Accessed August 30, 2018
    PubMed
  • 9 Schmugge M, Speer O, Kroiss S. , et al. Monitoring aspirin therapy in children after interventional cardiac catheterization: laboratory measures, dose response, and clinical outcomes. Eur J Pediatr 2015; 174 (07) 933-941
    CrossrefPubMedGoogle Scholar
  • 10 Yee DL, Dinu BR, Sun CW. , et al. Low prevalence and assay discordance of “aspirin resistance” in children. Pediatr Blood Cancer 2008; 51 (01) 86-92
    CrossrefPubMedGoogle Scholar
  • 11 Suzuki C, Yahata T, Okamoto-Hamaoka A. , et al. Utility of whole-blood aggregometry for evaluating anti-platelet therapy for Kawasaki disease. Pediatr Int 2013; 55 (05) 550-554
    CrossrefPubMedGoogle Scholar
  • 12 Truong DT, Johnson JT, Bailly DK. , et al. Platelet inhibition in shunted infants on aspirin at short and midterm follow-up. Pediatr Cardiol 2017; 38 (02) 401-409
    CrossrefPubMedGoogle Scholar
  • 13 Sirachainan N, Wijarn P, Chuansumrit A, Kadegasem P, Wongwerawattanakoon P, Soisamrong A. Aspirin resistance in children and young adults with splenectomized thalassemia diseases. Thromb Res 2015; 135 (05) 916-922
    CrossrefPubMedGoogle Scholar
  • 14 Li JS, Yow E, Berezny KY. , et al; PICOLO Investigators. Dosing of clopidogrel for platelet inhibition in infants and young children: primary results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial. Circulation 2008; 117 (04) 553-559
    CrossrefPubMedGoogle Scholar
  • 15 Heistein LC, Scott WA, Zellers TM. , et al. Aspirin resistance in children with heart disease at risk for thromboembolism: prevalence and possible mechanisms. Pediatr Cardiol 2008; 29 (02) 285-291
    CrossrefPubMedGoogle Scholar
  • 16 Cholette JM, Mamikonian L, Alfieris GM, Blumberg N, Lerner NB. Aspirin resistance following pediatric cardiac surgery. Thromb Res 2010; 126 (03) 200-206
    CrossrefPubMedGoogle Scholar
  • 17 Barburoglu M, Arat A. Flow diverters in the treatment of pediatric cerebrovascular diseases. AJNR Am J Neuroradiol 2017; 38 (01) 113-118
    CrossrefPubMedGoogle Scholar
  • 18 Emani S, Trainor B, Zurakowski D. , et al. Aspirin unresponsiveness predicts thrombosis in high-risk pediatric patients after cardiac surgery. J Thorac Cardiovasc Surg 2014; 148 (03) 810-814 , discussion 814–816
    CrossrefPubMedGoogle Scholar
  • 19 Rosenthal DN, Lancaster CA, McElhinney DB. , et al. Impact of a modified anti-thrombotic guideline on stroke in children supported with a pediatric ventricular assist device. J Heart Lung Transplant 2017; 36 (11) 1250-1257
    CrossrefPubMedGoogle Scholar
  • 20 Mir A, Frank S, Journeycake J. , et al. Aspirin resistance in single-ventricle physiology: aspirin prophylaxis is not adequate to inhibit platelets in the immediate postoperative period. Ann Thorac Surg 2015; 99 (06) 2158-2164
    CrossrefPubMedGoogle Scholar
  • 21 Jakubowski JA, Hoppe CC, Zhou C. , et al. Real-time dose adjustment using point-of-care platelet reactivity testing in a double-blind study of prasugrel in children with sickle cell anaemia. Thromb Haemost 2017; 117 (03) 580-588
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Linden MD. Using Platelet Function Testing to Guide Antiplatelet Therapy. Drug Dev Res 2013. ;74(8):517–525
  • 23 Price MJ, Berger PB, Teirstein PS. , et al; GRAVITAS Investigators. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011; 305 (11) 1097-1105
    CrossrefPubMedGoogle Scholar
  • 24 Collet J-P, Cuisset T, Rangé G. , et al; ARCTIC Investigators. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367 (22) 2100-2109
    CrossrefPubMedGoogle Scholar
  • 25 Schwartz KA, Schwartz DE, Ghosheh K, Reeves MJ, Barber K, DeFranco A. Compliance as a critical consideration in patients who appear to be resistant to aspirin after healing of myocardial infarction. Am J Cardiol 2005; 95 (08) 973-975
    CrossrefPubMedGoogle Scholar
  • 26 Monagle P, Cochrane A, Roberts R. , et al; Fontan Anticoagulation Study Group. A multicenter, randomized trial comparing heparin/warfarin and acetylsalicylic acid as primary thromboprophylaxis for 2 years after the Fontan procedure in children. J Am Coll Cardiol 2011; 58 (06) 645-651
    CrossrefPubMedGoogle Scholar
  • 27 Potter BJ, Leong-Sit P, Fernandes SM. , et al. Effect of aspirin and warfarin therapy on thromboembolic events in patients with univentricular hearts and Fontan palliation. Int J Cardiol 2013; 168 (04) 3940-3943
    CrossrefPubMedGoogle Scholar
  • 28 Schoeman JF, Janse van Rensburg A, Laubscher JA, Springer P. The role of aspirin in childhood tuberculous meningitis. J Child Neurol 2011; 26 (08) 956-962
    CrossrefPubMedGoogle Scholar
  • 29 Dallaire F, Fortier-Morissette Z, Blais S. , et al. Aspirin dose and prevention of coronary abnormalities in Kawasaki disease. Pediatrics 2017; 139 (06) e20170098
    CrossrefPubMedGoogle Scholar
  • 30 Michihata N, Matsui H, Fushimi K, Yasunaga H. Guideline-concordant treatment of Kawasaki disease with immunoglobulin and aspirin and the incidence of coronary artery aneurysm. Clin Pediatr (Phila) 2015; 54 (11) 1076-1080
    CrossrefPubMedGoogle Scholar
  • 31 Fernandez-Pineda I, Lopez-Gutierrez JC, Chocarro G, Bernabeu-Wittel J, Ramirez-Villar GL. Long-term outcome of vincristine-aspirin-ticlopidine (VAT) therapy for vascular tumors associated with Kasabach-Merritt phenomenon. Pediatr Blood Cancer 2013; 60 (09) 1478-1481
    CrossrefPubMedGoogle Scholar
  • 32 Heeney MM, Hoppe CC, Abboud MR. , et al; DOVE Investigators. A multinational trial of prasugrel for sickle cell vaso-occlusive events. N Engl J Med 2016; 374 (07) 625-635
    CrossrefPubMedGoogle Scholar
  • 33 Wessel DL, Berger F, Li JS. , et al; CLARINET Investigators. Clopidogrel in infants with systemic-to-pulmonary-artery shunts. N Engl J Med 2013; 368 (25) 2377-2384
    CrossrefPubMedGoogle Scholar
  • 34 Seltz LB, Bakel LA, Tiehen J. , et al. Efficacy and safety of clopidogrel in children with diarrhea associated hemolytic uremic syndrome. Thromb Res 2012; 130 (03) e26-e30
    CrossrefPubMedGoogle Scholar
  • 35 Drews T, Stiller B, Hübler M, Weng Y, Berger F, Hetzer R. Coagulation management in pediatric mechanical circulatory support. ASAIO J 2007; 53 (05) 640-645
    CrossrefPubMedGoogle Scholar
  • 36 Pasquali SK, Yow E, Jennings LK, Li JS. Platelet activity associated with concomitant use of clopidogrel and proton pump inhibitors in children with cardiovascular disease. Congenit Heart Dis 2010; 5 (06) 552-555
    CrossrefPubMedGoogle Scholar
  • 37 Copeland H, Nolan PE, Covington D, Gustafson M, Smith R, Copeland JG. A method for anticoagulation of children on mechanical circulatory support. Artif Organs 2011; 35 (11) 1018-1023
    CrossrefPubMedGoogle Scholar
  • 38 Hanke CA, Stiller B, Nakamura L, Grohmann J, Zieger B. Prophylactic use of clopidogrel in paediatric cardiac patients. Klin Padiatr 2012; 224 (03) 166-169
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Kim HJ, Choi E-H, Lim YJ, Kil HR. The usefulness of platelet-derived microparticle as biomarker of antiplatelet therapy in Kawasaki disease. J Korean Med Sci 2017; 32 (07) 1147-1153
    CrossrefPubMedGoogle Scholar
  • 40 Romlin BS, Wåhlander H, Strömvall-Larsson E, Synnergren M, Baghaei F, Jeppsson A. Monitoring of acetyl salicylic acid-induced platelet inhibition with impedance aggregometry in children with systemic-to-pulmonary shunts. Cardiol Young 2013; 23 (02) 225-232
    CrossrefPubMedGoogle Scholar
  • 41 Yahata T, Suzuki C, Yoshioka A, Hamaoka A, Ikeda K. Platelet activation dynamics evaluated using platelet-derived microparticles in Kawasaki disease. Circ J 2014; 78 (01) 188-193
    PubMedGoogle Scholar
  • 42 Jennings LK, Michelson AD, Jacoski MV, Tyagi A, Grgurevich S, Li JS. ; Picolo Investigators. Pharmacodynamic effects of clopidogrel in pediatric cardiac patients: a comparative study of platelet aggregation response. Platelets 2012; 23 (06) 430-438
    CrossrefPubMedGoogle Scholar