title: On-demand but not prophylactic treatment with FVIII concentrate increase thrombin activatable fibrinolysis inhibitor activation in severe haemophilia A patients.
abstract: BACKGROUND
  Thrombin activatable fibrinolysis inhibitor (TAFI) down-regulates fibrinolysis after activation by thrombin/thrombomodulin. We investigated the effect of treatment with FVIII concentrate on plasma levels of pro-TAFI and activated TAFI in haemophilia A patients.
  
  
  METHODS
  Samples were collected pre and posttreatment from patients treated prophylactically or on-demand. Pro-TAFI, TAFI/TAFIi and FVIII levels were measured in all samples.
  
  
  RESULTS
  Treatment had no effect on pro-TAFI levels. Pro-TAFI was similar in both patient groups but higher than in controls. Patients from the prophylactic treatment group had measurable FVIII levels pretreatment while in the treatment-on-demand group FVIII levels were ≤0.01 IU/mL. In the prophylactic treatment group, the levels of TAFI/TAFIi were significantly lower pre- and posttreatment (4.31 ± 3.14 and 3.48 ± 2.65 ng/mL respectively) than in the on-demand group (13.02 ± 3.47 and 14.87 ± 3.47 ng/mL respectively). This difference may be due to release of tissue factor at the injury site in the on-demand group. This could induce thrombin and TAFI activation within the clot counterbalancing fibrinolysis in these patients. In the prophylactic group, no injury existed, thus there was insufficient thrombin generation within the clot to activate TAFI.
  
  
  CONCLUSIONS
  These findings suggest that in patients to whom FVIII is administered on demand the fibrinolysis activity is more down regulated than in patients following a prophylactic treatment regime.
authors.affiliation: Haemostasis Department and Haemophilia Centre, Blood Transfusion Institute of Serbia, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Mikovic
authors.forename: B J
authors.initials: BJ
authors.lastname: Woodhams
authors.forename: M
authors.initials: M
authors.lastname: Holmström
authors.forename: I
authors.initials: I
authors.lastname: Elezovic
authors.forename: A
authors.initials: A
authors.lastname: Antovic
authors.forename: F
authors.initials: F
authors.lastname: Mobarrez
authors.forename: P
authors.initials: P
authors.lastname: Elfvinge
authors.forename: J P
authors.initials: JP
authors.lastname: Antovic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D025901:Carboxypeptidase B2 / Q000097:blood*; D002648:Child; D004789:Enzyme Activation; D005169:Factor VIII / Q000008:administration & dosage / Q000627:therapeutic use*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: C078147:F8 protein, human; D005169:Factor VIII; D025901:Carboxypeptidase B2