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 B(2) (11-dTXB(2)) 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-dTXB(2) levels did not correlate with aspirin resistance. Aspirin-resistant patients had higher 11-dTXB(2) 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.
authors: Department of Pediatrics, Division of Cardiology, The University of Texas Southwestern Medical Center, Children's Medical Center, Dallas, TX 75235, USA. lisa.heistein@childrens.com
authors: Lisa C
authors: LC
authors: Heistein
authors: William A
authors: WA
authors: Scott
authors: Thomas M
authors: TM
authors: Zellers
authors: David E
authors: DE
authors: Fixler
authors: Claudio
authors: C
authors: Ramaciotti
authors: Janna M
authors: JM
authors: Journeycake
authors: Matthew S
authors: MS
authors: Lemler
mesh_terms: D000293:Adolescent; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000150:complications* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013781:Texas / Q000453:epidemiology; D013923:Thromboembolism / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D001241:Aspirin