Lidia Tomkiewicz-Pajak1, Tomasz Wojcik2, Stefan Chłopicki3, Maria Olszowska4, Jacek Pajak5, Jakub Podolec6, Barbara Sitek2, Piotr Musiałek4, Paweł Rubis4, Monika Komar4, Piotr Podolec4. 1. 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. 2. Jagiellonian Centre for Experimental Therapeutics (JCET), Bobrzynskiego 14, Krakow, Poland. 3. 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. 4. Department of Cardiac and Cardiovascular Diseases, Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland. 5. Chair and Department of Children's Cardiology, Medical University of Silesia, Katowice, Poland. 6. Department of Interventional Cardiology, Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland.
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. CONCLUSION: 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.
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. CONCLUSION: 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.
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