Relation between aspirin resistance and thrombosis in high-risk pediatric patients following cardiac surgery: A prospective cohort study_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LI Dan ,  WANG Xu , LI Xia , LI Shoujun , YAN Jun

Department of Pediatric Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, P.R.China;

Corresponding author：

WANG Xu, Email: fwpicu@163.com

Keywords：

Congenital heart disease; aspirin; platelet inhibition; thrombosis; thromboelastograph

DOI：

10.7507/1007-4848.201805011

Video：

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Objective To determine the prevalence of aspirin (ASA) resistance in pediatric patients with congenital heart disease and evaluate whether postoperative thrombosis is associated with aspirin resistance.Methods A total of 52 patients undergoing high-risk congenital cardiac surgery were recruited in a prospective cohort study at Fuwai Hospital from August 2016 to December 2017. There were 29 males and 23 females with a median age of 8 months (6 d to 13 years). The response to aspirin was determined using the thromboelastography with platelet mapping (TEG-PM) system several days after administration. According to the arachidonic acid (AA) inhibition< 50% or not, they were divided into an ASA resistance group (n=14) and an ASA sensitivity group (n=38). Risk factors of ASA resistance were identified using univariate and multivariate analysis. Patients were monitored prospectively for three months for the development of a thrombosis event. Results Of 52 children analyzed, 14 (26.9%) were ASA resistance. The prevalence of thrombosis after ASA antiplatelet therapy was 5.9%. Dose escalation based on aspirin testing was performed in 3 of 14 patients, and the ASA sensitivity was observed in 1 patient. No correlation was found between ASA resistance and postoperative thrombosis (r=0.04, P=0.80).Conclusion Postoperative thrombosis is not associated with aspirin resistance in these patients. Our findings also suggest that resistance may be due to lack of aspirin doses, monitoring of aspirin therapy and consideration of dose adjustment or alternative agents for unresponsive patients.

Citation： LI Dan, WANG Xu, LI Xia, LI Shoujun, YAN Jun. Relation between aspirin resistance and thrombosis in high-risk pediatric patients following cardiac surgery: A prospective cohort study. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2019, 26(2): 137-141. doi: 10.7507/1007-4848.201805011 Copy

1.	Silvey M, Brandão LR. Risk factors, prophylaxis, and treatment of venous thromboembolism in congenital heart disease patients. Front Pediatr, 2017, 5: 146.
2.	Monagle P, Cochrane A, Roberts R, et al. 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(6): 645-651.
3.	Manlhiot C, Menjak IB, Brandão LR, et al. Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery. Circulation, 2011, 124(14): 1511-1519.
4.	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.
5.	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(24): 2622-2703.
6.	龚艳君, 邱林, 屈晨雪, 等. 血栓弹力图评价冠状动脉介入治疗术后抗血小板药物疗效及与预后的关系. 中华全科医学, 2016, 14(8): 1289-1292.
7.	Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost, 2003, 1(8): 1710-1713.
8.	中华医学会心血管病学分会, 中华心血管病杂志编辑委员会. 抗血小板药物治疗反应多样性临床检测和处理的中国专家建议. 中华心血管病杂志, 2014, 42(12): 986-991.
9.	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(2): 285-291.
10.	Schmugge M, Speer O, Kroiss S, et al. Aspirin resistance in children after interventional cardiac catheterization. ASH Annual Meeting, 2008, 112(11): 691.
11.	Cholette JM, Mamikonian L, Alfieris GM, et al. Aspirin resistance following pediatric cardiac surgery. Thromb Res, 2010, 126(3): 200-206.
12.	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(3): 810-814.
13.	Emani S, Zurakowski D, Mulone M, et al. Platelet testing to guide aspirin dose adjustment in pediatric patients after cardiac surgery. J Thorac Cardiovasc Surg, 2017, 154(5): 1723-1730.
14.	Paniccia R, Priora R, Liotta AA, et al. Platelet function tests: a comparative review. Vasc Health Risk Manag, 2015, 11: 133-148.
15.	Madsen EH, Saw J, Kristensen SR, et al. Long-term aspirin and clopidogrel response evaluated by light transmission aggregometry, VerifyNow, and thrombelastography in patients undergoing percutaneous coronary intervention. Clin Chem, 2010, 56(5): 839-847.

1. Silvey M, Brandão LR. Risk factors, prophylaxis, and treatment of venous thromboembolism in congenital heart disease patients. Front Pediatr, 2017, 5: 146.
2. Monagle P, Cochrane A, Roberts R, et al. 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(6): 645-651.
3. Manlhiot C, Menjak IB, Brandão LR, et al. Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery. Circulation, 2011, 124(14): 1511-1519.
4. 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.
5. 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(24): 2622-2703.
6. 龚艳君, 邱林, 屈晨雪, 等. 血栓弹力图评价冠状动脉介入治疗术后抗血小板药物疗效及与预后的关系. 中华全科医学, 2016, 14(8): 1289-1292.
7. Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost, 2003, 1(8): 1710-1713.
8. 中华医学会心血管病学分会, 中华心血管病杂志编辑委员会. 抗血小板药物治疗反应多样性临床检测和处理的中国专家建议. 中华心血管病杂志, 2014, 42(12): 986-991.
9. 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(2): 285-291.
10. Schmugge M, Speer O, Kroiss S, et al. Aspirin resistance in children after interventional cardiac catheterization. ASH Annual Meeting, 2008, 112(11): 691.
11. Cholette JM, Mamikonian L, Alfieris GM, et al. Aspirin resistance following pediatric cardiac surgery. Thromb Res, 2010, 126(3): 200-206.
12. 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(3): 810-814.
13. Emani S, Zurakowski D, Mulone M, et al. Platelet testing to guide aspirin dose adjustment in pediatric patients after cardiac surgery. J Thorac Cardiovasc Surg, 2017, 154(5): 1723-1730.
14. Paniccia R, Priora R, Liotta AA, et al. Platelet function tests: a comparative review. Vasc Health Risk Manag, 2015, 11: 133-148.
15. Madsen EH, Saw J, Kristensen SR, et al. Long-term aspirin and clopidogrel response evaluated by light transmission aggregometry, VerifyNow, and thrombelastography in patients undergoing percutaneous coronary intervention. Clin Chem, 2010, 56(5): 839-847.

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Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Relation between aspirin resistance and thrombosis in high-risk pediatric patients following cardiac surgery: A prospective cohort study

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