title: Aspirin resistance in adult patients after Fontan surgery.
abstract: BACKGROUND
  Thrombotic complications are common in adult patients who have had a Fontan operation early in life for treatment of congenital heart disease.
  
  
  OBJECTIVE
  To characterize platelet function and responsiveness to aspirin in relation to thrombogenesis, systemic inflammation, and markers of endothelial function in adults with Fontan circulation (FC).
  
  
  METHODS
  Thirty-four FC patients (age 18-40years; 62% taking aspirin chronically and 38% not taking aspirin) and 32 age- and sex-matched healthy controls were studied. Platelet function was evaluated by measurement of basal concentrations of thromboxane B2 (TXB2) and sCD40L and ex-vivo generation of TXB2 and sCD40L. Plasma concentrations of thrombin-antithrombin, endothelin-1, vWF, IL-6, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 also were measured.
  
  
  RESULTS
  Platelet numbers were significantly lower in FC patients than in controls, but the patients had significantly higher platelet activity, as evidenced by higher TXB2 and sCD40L concentrations and higher ex vivo generation of TXB2. Chronic aspirin treatment had no effect on plasma concentrations of TXB2 and sCD40L in FC, but in 52% of aspirin-treated FC subjects, TXB2 concentrations remained elevated at 60min of TXB2 generation, indicating aspirin resistance. In addition, FC patients had increased levels of thrombin-antithrombin, endothelin-1, vWF, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 but not of IL-6.
  
  
  CONCLUSIONS
  Adults with FC had lower platelet numbers but increased platelet activity, increased thrombogenesis, systemic inflammation, and endothelial dysfunction. A significant proportion of aspirin-treated FC adults had aspirin resistance, which may be at least in part responsible for their increased incidence of thrombotic complications.
authors.affiliation: Department of Cardiac and Cardiovascular Diseases, Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland. Electronic address: ltom@wp.pl.
authors.forename: Lidia
authors.initials: L
authors.lastname: Tomkiewicz-Pajak
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wojcik
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, Krakow, Poland; Department of Experimental Pharmacology, Chair of Pharmacology, Jagiellonian University Medical College, Grzegorzecka 16, Krakow, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Chłopicki
authors.affiliation: Department of Cardiac and Cardiovascular Diseases, Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Olszowska
authors.affiliation: Chair and Department of Children's Cardiology, Medical University of Silesia, Katowice, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Pajak
authors.affiliation: Department of Interventional Cardiology, Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Podolec
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
authors.affiliation: Department of Cardiac and Cardiovascular Diseases, Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Musiałek
authors.affiliation: Department of Cardiac and Cardiovascular Diseases, Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Rubis
authors.affiliation: Department of Cardiac and Cardiovascular Diseases, Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Komar
authors.affiliation: Department of Cardiac and Cardiovascular Diseases, Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Podolec
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D019013:CD40 Antigens / Q000378:metabolism*; D004351:Drug Resistance; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018729:Fontan Procedure / Q000009:adverse effects* / Q000379:methods; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010976:Platelet Count; D011183:Postoperative Complications / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D013929:Thromboxane B2 / Q000378:metabolism*
chemical_list: D019013:CD40 Antigens; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D001241:Aspirin
keywords: Aspirin resistance; Endothelial function; Fontan surgery; Inflammation; Platelet reactivity; Thromboxane B2 generation test