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

Lisa C Heistein, William A Scott, Thomas M Zellers, David E Fixler, Claudio Ramaciotti, Janna M Journeycake, Matthew S Lemler

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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

Keywords

  • Aspirin
  • Congenital heart disease
  • Platelets
  • Thrombosis

ASJC Scopus subject areas

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

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