This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.ABSTRACTAspirin is the most common antiplatelet agent used in children and has specific indications in pediatric cardiac surgery, pediatric stroke, Kawasaki disease and other disorders for the prevention and treatment of thrombotic complications. Recent evidence from many adult studies has linked aspirin treatment failure (e.g. occurrence of thrombotic events) to aspirin resistance, a phenomenon of persistent platelet activity observed with in vitro testing of platelets from some patients taking aspirin. High reported prevalence rates of aspirin resistance in adults coupled with the drug's widespread use worldwide have sparked intense research interest, such that aspirin resistance has become an active area of study in adults. In contrast, there exists no prevalence, natural history or outcome data on aspirin resistance in children. We hypothesize that aspirin resistance occurs as commonly in children as it does in adults and that it is associated with treatment failure. We will addres this hypothesis through the following specific aims: 1) determine the prevalence of aspirin resistance in pediatric patients receiving aspirin and 2) follow outcomes in pediatric patients receiving aspirin to determine the clinical relevance of aspirin resistance. Because the best method for identifying aspirin resistance is unknown, we will assess platelet function in our subjects using several different laboratory assay methods and identify the method that correlates best with clinical outcome. This work will provide important information necesary for directing future studies of aspirin use and resistance in children as well as allow banking of DNA specimens for planned gene-association studies of aspirin resistance.
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