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Aspirin resistance in infants with shunt-dependent congenital heart disease

Published online by Cambridge University Press:  26 July 2021

Wonshill Koh*
Affiliation:
The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Megan Rodts
Affiliation:
The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Ashley Nebbia
Affiliation:
Division of Pharmacy, The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Jaclyn Sawyer
Affiliation:
Division of Pharmacy, The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Brandon Henry
Affiliation:
The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
David S. Cooper
Affiliation:
The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
*
Author for correspondence: Wonshill Koh, MD, PhD, The Heart Institute, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 2003, Cincinnati, OH45229, USA. Tel: 513 803 5541; Fax: 513-636-3952. E-mail: [email protected]

Abstract

Introduction:

Patients with cyanotic heart disease are at an increased risk of developing thrombosis. Aspirin has been the mainstay of prophylactic anticoagulation for shunt-dependent patients with several reports of prevalent aspirin resistance, especially in neonates. We investigate the incidence of aspirin resistance and its relationship to thrombotic events and mortality in a cohort of infants with shunt-dependent physiology.

Methods:

Aspirin resistance was assessed using the VerifyNow™ test on infants with single-ventricle physiology following shunt-dependent palliation operations. In-hospital thrombotic events and mortality data were collected. Statistical analysis was performed to evaluate the effect of aspirin resistance on in-hospital thrombotic events and mortality risk.

Results:

Forty-nine patients were included with 41 of these patients being neonates. Six patients (12%) were aspirin resistant. A birth weight < 2500 grams was a significant factor associated with aspirin resistance (p = 0.04). Following a dose increase or additional dose administration, all patients with initial aspirin resistance had a normal aspirin response. There was no statistically significant difference between aspirin resistance and non-resistance groups with respect to thrombotic events. However, a statistically significant incidence of in-hospital mortality in the presence of thrombotic events was observed amongst aspirin-resistant patients (p = 0.04) in this study.

Conclusion:

Low birth weight was associated with a higher incidence of aspirin resistance. Inadequate initial dosing appears to be the primary reason for aspirin resistance. The presence of both thrombotic events and aspirin resistance was associated with significantly higher in-hospital mortality indicating that these patients warrant closer monitoring.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Algra, SO, Breur, JM, Evens, FC, et al. Improving surgical outcome following the Norwood procedure. Neth Heart J 2011; 19: 369372.CrossRefGoogle ScholarPubMed
Baba, K, Kotani, Y, Chetan, D, et al. Hybrid versus Norwood strategies for single-ventricle palliation. Circulation 2012; 126 (11 Suppl 1): S123131.CrossRefGoogle ScholarPubMed
Davies, RR, Pizarro, C. Decision-Making for Surgery in the Management of Patients with Univentricular Heart. Front Pediatr 2015; 3: 61.CrossRefGoogle ScholarPubMed
Ohye, RG, Schranz, D, D’Udekem, Y. Current Therapy for Hypoplastic Left Heart Syndrome and Related Single Ventricle Lesions. Circulation 2016; 134: 12651279.CrossRefGoogle ScholarPubMed
Ohye, RG, Sleeper, LA, Mahony, L, et al. Comparison of shunt types in the Norwood procedure for single-ventricle lesions. N Engl J Med 2010; 362: 19801992.CrossRefGoogle ScholarPubMed
Petit, CJ. Staged single-ventricle palliation in 2011: outcomes and expectations. Congenit Heart Dis 2011; 6: 406416.CrossRefGoogle ScholarPubMed
Petrucci, O, O’Brien, SM, Jacobs, ML, et al. Risk factors for mortality and morbidity after the neonatal Blalock-Taussig shunt procedure. Ann Thorac Surg 2011; 92: 642651; discussion 651–642.CrossRefGoogle ScholarPubMed
Fenton, KN, Siewers, RD, Rebovich, B, et al. Interim mortality in infants with systemic-to-pulmonary artery shunts. Ann Thorac Surg 2003; 76: 152156; discussion 156–157.CrossRefGoogle ScholarPubMed
Tabbutt, S, Ghanayem, N, Ravishankar, C, et al. Risk factors for hospital morbidity and mortality after the Norwood procedure: A report from the Pediatric Heart Network Single Ventricle Reconstruction trial. J Thorac Cardiovasc Surg 2012; 144: 882895.CrossRefGoogle ScholarPubMed
Agarwal, A, Firdouse, M, Brar, N, et al. Incidence and Management of Thrombotic and Thromboembolic Complications Following the Superior Cavopulmonary Anastomosis Procedure: A Literature Review. Clin Appl Thromb Hemost 2018; 24: 405415.CrossRefGoogle ScholarPubMed
Cholette, JM, Mamikonian, L, Alfieris, GM, et al. Aspirin resistance following pediatric cardiac surgery. Thromb Res 2010; 126: 200206.CrossRefGoogle ScholarPubMed
Giglia, TM, Massicotte, MP, Tweddell, JS, et al. Prevention and treatment of thrombosis in pediatric and congenital heart disease: a scientific statement from the American Heart Association. Circulation 2013; 128: 26222703.CrossRefGoogle ScholarPubMed
Manlhiot, C, Menjak, IB, Brandao, LR, et al. Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery. Circulation 2011; 124: 15111519.CrossRefGoogle ScholarPubMed
Li, JS, Yow, E, Berezny, KY, et al. Clinical outcomes of palliative surgery including a systemic-to-pulmonary artery shunt in infants with cyanotic congenital heart disease: does aspirin make a difference?. Circulation 2007; 116: 293297.CrossRefGoogle Scholar
Motz, R, Wessel, A, Ruschewski, W, et al. Reduced frequency of occlusion of aorto-pulmonary shunts in infants receiving aspirin. Cardiol Young 1999; 9: 474477.CrossRefGoogle ScholarPubMed
Al Jubair, KA, Al Fagih, MR, Al Jarallah, AS, et al. Results of 546 Blalock-Taussig shunts performed in 478 patients. Cardiol Young 1998; 8: 486490.CrossRefGoogle ScholarPubMed
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: 810814; discussion814–816.CrossRefGoogle ScholarPubMed
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: 21582164.CrossRefGoogle Scholar
Rand, ML, Kuhle, S. Platelets and platelet function testing in children. Prog Pediatr Cardiol 2005; 21: 6369.CrossRefGoogle Scholar
Sambu, N, Curzen, N. Monitoring the effectiveness of antiplatelet therapy: opportunities and limitations. Br J Clin Pharmacol 2011; 72: 683696.CrossRefGoogle ScholarPubMed
Hussein, HM, Emiru, T, Georgiadis, AL, et al. Assessment of platelet inhibition by point-of-care testing in neuroendovascular procedures. AJNR Am J Neuroradiol 2013; 34: 700706.CrossRefGoogle ScholarPubMed
Nielsen, HL, Kristensen, SD, Thygesen, SS, et al. Aspirin response evaluated by the VerifyNow Aspirin System and light transmission aggregometry. Thromb Res 2008; 123: 267273.CrossRefGoogle ScholarPubMed
Cholette, JM, Rubenstein, JS, Alfieris, GM, et al. Elevated risk of thrombosis in neonates undergoing initial palliative cardiac surgery. Ann Thorac Surg 2007; 84: 13201325.CrossRefGoogle ScholarPubMed
Hu, W, Tong, J, Kuang, X, et al. Influence of proton pump inhibitors on clinical outcomes in coronary heart disease patients receiving aspirin and clopidogrel: A meta-analysis. Medicine (Baltimore) 2018; 97: e9638.CrossRefGoogle ScholarPubMed
Lev, EI, Ramabadran, RS, Guthikonda, S, et al. Effect of ranitidine on the antiplatelet effects of aspirin in healthy human subjects. Am J Cardiol 2007; 99: 124128.CrossRefGoogle ScholarPubMed
Yee, DL, Dinu, BR, Sun, CW, et al. Low prevalence and assay discordance of “aspirin resistance” in children. Pediatr Blood Cancer 2008; 51: 8692.CrossRefGoogle ScholarPubMed
Revel-Vilk, S. The conundrum of neonatal coagulopathy. Hematology Am Soc Hematol Educ Program 2012; 2012: 450454.CrossRefGoogle ScholarPubMed
Romlin, BS, Wahlander, H, Stromvall-Larsson, E, et al. Monitoring of acetyl salicylic acid-induced platelet inhibition with impedance aggregometry in children with systemic-to-pulmonary shunts. Cardiol Young 2013; 23: 225232.CrossRefGoogle ScholarPubMed