title: Effective tranexamic acid concentration for 95% inhibition of tissue-type plasminogen activator induced hyperfibrinolysis in children with congenital heart disease: A prospective, controlled, in-vitro study.
abstract: BACKGROUND
  Although recent studies have assessed tranexamic acid (TXA) pharmacokinetics in different subgroups, the effective concentration of TXA required to completely inhibit fibrinolysis remains to be determined.
  
  
  OBJECTIVE
  An in-vitro determination of the effective TXA concentration needed for 95% inhibition (EC95) of tissue-type plasminogen activator (t-PA) activated fibrinolysis, using an experimental model designed for thromboelastometry (ROTEM).
  
  
  METHODS
  A prospective interventional study.
  
  
  METHODS
  Department of Anaesthesiology, Queen Fabiola Children's University Hospital and Laboratory of Haematology and Haemostasis, Brugmann University Hospital. Patients were enrolled between June 2013 and October 2014.
  Twenty children, aged between 1 and 10 years, undergoing elective cardiac catheterisation were included (10 with cyanotic and 10 with noncyanotic diseases). Exclusion criteria were child requiring a procedure in a moribund state. Ten adult volunteers were also included as controls.
  
  
  METHODS
  Citrated whole blood samples were obtained from children and volunteers.
  
  
  METHODS
  The extrinsic coagulation pathway was activated by tissue factor using the EXTEM test on ROTEM. The degree of lysis measured 30 min (LI30) after the clotting time (CT), and clot amplitudes measured at different times were recorded at baseline, after addition of 1535 units t-PA ml(-1), and following the addition of increasing TXA concentrations in t-PA activated samples.
  
  
  RESULTS
  The concentration-effect analysis performed with lysis index after 30 min (LI30) allowed the determination of TXA efficacy concentration 50% (EC50), and calculation of the EC95, which was significantly lower in cardiac surgery children than in adults [8.6 μg ml(-1); 95% confidence interval (95% CI) 6.9 to 14.9 versus 11.3 μg ml(-1); 95% CI 10.6 to 12.9, P < 0.001].
  
  
  CONCLUSIONS
  In this in-vitro study, we observed that the EC95 TXA concentration that completely inhibited t-PA induced hyperfibrinolysis in children with congenital heart was significantly lower than the concentration required in healthy adult volunteers. Further studies are needed to confirm that this plasma concentration can effectively inhibit fibrinolysis activation in children undergoing cardiac surgery.
authors.affiliation: From the Laboratory of Haemostasis, Brugmann University Hospital, Université libre de Bruxelles ULB, Brussels, Belgium (LR, DCFN, AD), Department of Anesthesiology, Peri-operative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA (DF), Department of Anaesthesiology, Queen Fabiola Children's University Hospital (CST, PVDL), Paediatric Intensive Care Unit, Queen Fabiola Children's Hospital (AW), and Chemistry Laboratory, Brugmann University Hospital, Université libre de Bruxelles ULB, Brussels, Belgium (DB).
authors.forename: Laurence
authors.initials: L
authors.lastname: Rozen
authors.forename: David
authors.initials: D
authors.lastname: Faraoni
authors.forename: Cristel
authors.initials: C
authors.lastname: Sanchez Torres
authors.forename: Ariane
authors.initials: A
authors.lastname: Willems
authors.forename: Denis C F
authors.initials: DC
authors.lastname: Noubouossie
authors.forename: Dragos
authors.initials: D
authors.lastname: Barglazan
authors.forename: Philippe
authors.initials: P
authors.lastname: Van der Linden
authors.forename: Anne
authors.initials: A
authors.lastname: Demulder
mesh_terms: D000328:Adult; D000933:Antifibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006330:Heart Defects, Congenital / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000097:blood; D014148:Tranexamic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D010959:Tissue Plasminogen Activator