title: Evaluation of the overall haemostatic effect of recombinant factor VIIa by measuring thrombin generation and stability of fibrin clots.
abstract: It has been reported that thrombin generation test (TGT) may be a useful tool to monitor recombinant factor VIIa (rFVIIa). However, TGT does not reflect the stability of fibrin clot and its resistance to fibrinolysis which are crucial. Using whole-blood thromboelastography (TEG) and tissue plasminogen activator (tPA), we developed an in-vitro model to assess fibrin clot stability. Fibrin fibres were thicker in haemophiliacs compared with controls (P < 0.0001). After addition of rFVIIa 90 μg kg(-1), the diameter of fibrin fibres was dramatically decreased (P = 0.006). TEG-tPA assay showed a dose-dependent improvement of clot stability in the presence of rFVIIa. These data demonstrate a significant correlation between fibrin clot structure and its stability (P = 0.001). We also showed a correlation between thrombin generating capacity and clot resistance to fibrinolysis. Despite this overall correlation, a relatively large spreading around a general trend was observed, suggesting that the two assays bring complementary information on the haemostatic effect of rFVIIa.
authors: Unite d'Hemostase Clinique, Hopital Edouard Herriot, Lyon EA 4174, France. ydargaud@univ-lyon1.fr
authors: Y
authors: Y
authors: Dargaud
authors: C
authors: C
authors: Prevost
authors: A
authors: A
authors: Lienhart
authors: J
authors: J
authors: Claude Bordet
authors: C
authors: C
authors: Negrier
mesh_terms: D000704:Analysis of Variance; D001777:Blood Coagulation / Q000187:drug effects*; D015942:Factor VIIa / Q000627:therapeutic use*; D005337:Fibrin / Q000187:drug effects*; D006467:Hemophilia A / Q000188:drug therapy* / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D011994:Recombinant Proteins / Q000627:therapeutic use; D013916:Thrombelastography / Q000379:methods; D013917:Thrombin / Q000096:biosynthesis*; D010959:Tissue Plasminogen Activator / Q000032:analysis
chemical_list: D006490:Hemostatics; D011994:Recombinant Proteins; D005337:Fibrin; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin; D010959:Tissue Plasminogen Activator