Aspirin Resistance in Children with Heart Disease at Risk for Thromboembolism: Prevalence and Possible Mechanisms

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• 作者：Lisa C. Heistein ; William A. Scott ; Thomas M. Zellers ; David E. Fixler ; Claudio Ramaciotti ; Janna M. Journeycake and Matthew S. Lemler
• 关键词：Aspirin ; Thrombosis ; Platelets ; Congenital heart disease
• 刊名：Pediatric Cardiology
• 出版年：2008
• 出版时间：March, 2008
• 年：2008
• 卷：29
• 期：2
• 页码：285-291
• 全文大小：246.9 KB

文摘

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.