title: The thrombin generation assay distinguishes inhibitor from non-inhibitor patients with severe haemophilia A.
abstract: BACKGROUND
  Patients with haemophilia A (HA) have impaired thrombin generation (TG) capacity and TG assay (TGA) values are linearly related to plasma factor VIII (FVIII) levels.
  
  
  OBJECTIVE
  This study carried out in patients with unmeasurable FVIII (<1 IU dL(-1) ) was aimed at unravelling any difference in TG capacity in patients with or without inhibitors.
  
  
  METHODS
  Blood samples were collected from patients in a non-bleeding state, after a 5-day wash-out period from last treatment.
  
  
  RESULTS
  TGA was performed in 102 patients with severe HA (15% with high-responding inhibitors; 51% with null F8 mutations, that as expected were more prevalent in inhibitor than in non-inhibitor patients). TG capacity was significantly lower in inhibitor than non-inhibitor patients and in those with null mutations than in those with non-null mutations. When the TG capacity was evaluated only in patients with null mutations with and without inhibitors it was lower in the presence of inhibitors.
  
  
  CONCLUSIONS
  This study shows a greater TG impairment in inhibitor patients irrespective of FVIII levels, inhibitor titre and F8 mutation type, suggesting a role for the TGA in unravelling functional interferences of anti-FVIII inhibitors on coagulation system activation.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Mancuso
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Chantarangkul
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Clerici
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Fasulo
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Padovan
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Scalambrino
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Peyvandi
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tripodi
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D001780:Blood Coagulation Tests; D005169:Factor VIII / Q000235:genetics; D005838:Genotype; D006467:Hemophilia A / Q000097:blood* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012720:Severity of Illness Index; D013917:Thrombin / Q000032:analysis*
chemical_list: D057134:Antibodies, Neutralizing; D005169:Factor VIII; D013917:Thrombin
keywords: F8 mutations; endogenous thrombin potential; inhibitors; severe haemophilia A; thrombin generation assay