Aspirin resistance in adult patients after Fontan surgery

Int J Cardiol. 2015 Feb 15;181:19-26. doi: 10.1016/j.ijcard.2014.11.219. Epub 2014 Nov 27.


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.

Keywords: Aspirin resistance; Endothelial function; Fontan surgery; Inflammation; Platelet reactivity; Thromboxane B2 generation test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspirin / pharmacology*
  • CD40 Antigens / metabolism*
  • Drug Resistance
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Female
  • Fontan Procedure / adverse effects*
  • Fontan Procedure / methods
  • Heart Defects, Congenital / surgery*
  • Humans
  • Inflammation* / blood
  • Inflammation* / etiology
  • Inflammation* / physiopathology
  • Male
  • Neutrophil Activation / drug effects*
  • Platelet Activation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Count
  • Postoperative Complications* / blood
  • Postoperative Complications* / physiopathology
  • Postoperative Complications* / prevention & control
  • Thrombosis* / blood
  • Thrombosis* / etiology
  • Thrombosis* / physiopathology
  • Thrombosis* / prevention & control
  • Thromboxane B2 / metabolism*


  • CD40 Antigens
  • Platelet Aggregation Inhibitors
  • Thromboxane B2
  • Aspirin