Aspirin resistance in children with heart disease at risk for thromboembolism: Prevalence and possible mechanisms

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Abstract

Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B2 (11-dTXB2) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p < 0.01). 11-dTXB2 levels did not correlate with aspirin resistance. Aspirin-resistant patients had higher 11-dTXB2 levels before (7297 vs. 4160 pg/mg creatinine; p < 0.01) and after (2153 vs. 1412 pg/mg; p = 0.03) aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

Original languageEnglish (US)
Pages (from-to)285-291
Number of pages7
JournalPediatric Cardiology
Volume29
Issue number2
DOIs
StatePublished - Mar 2008

Fingerprint

Thromboembolism
Aspirin
Heart Diseases
Thromboxanes
Adenosine Diphosphate
Blood Platelets
Epinephrine
Platelet Activation
Prostaglandin-Endoperoxide Synthases
Creatinine
Urine

Keywords

  • Aspirin
  • Congenital heart disease
  • Platelets
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pediatrics, Perinatology, and Child Health

Cite this

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title = "Aspirin resistance in children with heart disease at risk for thromboembolism: Prevalence and possible mechanisms",
abstract = "Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5{\%}-51{\%} prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B2 (11-dTXB2) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26{\%}. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p < 0.01). 11-dTXB2 levels did not correlate with aspirin resistance. Aspirin-resistant patients had higher 11-dTXB2 levels before (7297 vs. 4160 pg/mg creatinine; p < 0.01) and after (2153 vs. 1412 pg/mg; p = 0.03) aspirin, with a similar percentage decrease in thromboxane (70.5{\%} vs. 66.1{\%}; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.",
keywords = "Aspirin, Congenital heart disease, Platelets, Thrombosis",
author = "Heistein, {Lisa C} and Scott, {William A} and Zellers, {Thomas M} and Fixler, {David E} and Claudio Ramaciotti and Journeycake, {Janna M} and Lemler, {Matthew S}",
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T1 - Aspirin resistance in children with heart disease at risk for thromboembolism

T2 - Prevalence and possible mechanisms

AU - Heistein, Lisa C

AU - Scott, William A

AU - Zellers, Thomas M

AU - Fixler, David E

AU - Ramaciotti, Claudio

AU - Journeycake, Janna M

AU - Lemler, Matthew S

PY - 2008/3

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N2 - Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B2 (11-dTXB2) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p < 0.01). 11-dTXB2 levels did not correlate with aspirin resistance. Aspirin-resistant patients had higher 11-dTXB2 levels before (7297 vs. 4160 pg/mg creatinine; p < 0.01) and after (2153 vs. 1412 pg/mg; p = 0.03) aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

AB - Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B2 (11-dTXB2) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p < 0.01). 11-dTXB2 levels did not correlate with aspirin resistance. Aspirin-resistant patients had higher 11-dTXB2 levels before (7297 vs. 4160 pg/mg creatinine; p < 0.01) and after (2153 vs. 1412 pg/mg; p = 0.03) aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

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KW - Congenital heart disease

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KW - Thrombosis

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