title: Abnormalities in blood coagulation, fibrinolysis, and platelet activation in adult patients after the Fontan procedure.
abstract: BACKGROUND
  Thrombosis occurs in up to 30% of patients with various forms of congenital single ventricle after the Fontan procedure. We investigated hemostatic abnormalities in adult Fontan patients.
  
  
  METHODS
  Forty-eight Fontan patients between ages 18 and 40 years, including 10 (21%) patients with previous thromboembolism 5 to 15 years after surgery, and 35 control subjects matched for age and sex were studied. Coagulation factors and inhibitors, together with markers of fibrinolysis, platelets, and endothelial activation, were determined in peripheral venous blood plasma.
  
  
  RESULTS
  Compared with control subjects, Fontan patients showed lower, although mostly within normal ranges, values of all coagulation factors, as well as reduced free protein S, in association with higher antithrombin and free tissue factor pathway inhibitor levels. Thrombin generation, reflected by prothrombin fragment 1.2, and platelet activation markers were increased in Fontan patients. The plasma clot lysis time was prolonged in Fontan patients, which was associated with an increased activity of thrombin-activatable fibrinolysis inhibitor. Fontan patients with previous thromboembolism had lower oxygen saturation, coagulation factors V and VIII, and free protein S, and increased von Willebrand factor, soluble CD40 ligand, and P-selectin. Other laboratory or clinical parameters were not associated with prior thrombotic episodes.
  
  
  CONCLUSIONS
  Adult Fontan patients are characterized by enhanced platelet activation and endothelial injury, heightened thrombin formation, and impaired fibrinolysis. Patients showed reduced free protein S levels, increased platelet activation, and endothelial damage after thromboembolic events observed late after Fontan surgery. Our findings indicate novel prothrombotic mechanisms in adult Fontan patients, which might help to optimize thromboprophylaxis.
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; John Paul II Hospital, Krakow, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Tomkiewicz-Pajak
authors.affiliation: Department of Adult Congenital Heart Diseases, Institute of Cardiology, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Hoffman
authors.affiliation: 1st Department of Cardiology, University of Medical Sciences, Poznan, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Trojnarska
authors.affiliation: Department of Adult Congenital Heart Diseases, Institute of Cardiology, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lipczyńska
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; John Paul II Hospital, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Podolec
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; John Paul II Hospital, Krakow, Poland. Electronic address: mmundas@cyf-kr.edu.pl.
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
mesh_terms: D000293:Adolescent; D000328:Adult; D001778:Blood Coagulation Disorders / Q000453:epidemiology*; D005260:Female; D005342:Fibrinolysis; D018729:Fontan Procedure; D006801:Humans; D008297:Male; D015539:Platelet Activation; D011183:Postoperative Complications / Q000453:epidemiology*; D013923:Thromboembolism / Q000453:epidemiology*; D013997:Time Factors; D055815:Young Adult