title: Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B.
abstract: In haemophilia patients, a relationship is usually observed between the clinical expression of the disease and plasmatic factor VIII/factor IX (FVIII/FIX) activity. However, it is known from clinical experience, that some haemophilia patients, despite similar FVIII/FIX plasma levels, could exhibit different bleeding phenotype. After determining preanalytical test conditions, we evaluated the thrombin generation capacity from haemophilia plasma samples in various conditions and the potential usefulness of thrombin generation test (TGT) in haemophilia patients. In a series of 46 haemophilia patients (34 haemophilia A and 12 haemophilia B patients), we found a significant correlation between plasmatic FVIII/FIX levels and endogenous thrombin potential (ETP), peak and time to peak obtained by thrombin generation measurement. In addition, a correlation was found between severe clinical bleeding phenotype and ETP. Our results suggest that TGT could be a promising tool to evaluate haemostasis capacity in patients with haemophilia. Our ex vivo results, obtained 24 hours after FVIII concentrate administration, showed that in patients presenting similar plasmatic FVIIII levels, thrombin generation capacity may be significantly different. These results suggest that in patients with haemophilia, TGT could be useful for individually tailoring prophylactic regimens as well as for adapting clotting factors infusions in surgical situations, in addition to FVIII/FIX plasma clotting activities.
authors.affiliation: Laboratoire d'Hemostase, Hopital Edouard Herriot, Lyon, France. ydargaud@univ-lyon1.fr
authors.forename: Yesim
authors.initials: Y
authors.lastname: Dargaud
authors.forename: Suzette
authors.initials: S
authors.lastname: Béguin
authors.forename: Anne
authors.initials: A
authors.lastname: Lienhart
authors.forename: Raed
authors.initials: R
authors.lastname: Al Dieri
authors.forename: Christine
authors.initials: C
authors.lastname: Trzeciak
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Bordet
authors.forename: H Coenraad
authors.initials: HC
authors.lastname: Hemker
authors.forename: Claude
authors.initials: C
authors.lastname: Negrier
mesh_terms: D000328:Adult; D001780:Blood Coagulation Tests / Q000592:standards*; D005164:Factor IX / Q000032:analysis; D005169:Factor VIII / Q000032:analysis; D006467:Hemophilia A / Q000097:blood*; D002836:Hemophilia B / Q000097:blood*; D006470:Hemorrhage / Q000175:diagnosis; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D010641:Phenotype; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: C078147:F8 protein, human; D005169:Factor VIII; D005164:Factor IX; D013917:Thrombin