title: Recombinant factor VIIa improves clot formation but not fibrolytic potential in patients with cirrhosis and during liver transplantation.
abstract: Cirrhosis is associated with a bleeding tendency, which is particularly pronounced during orthotopic liver transplantation (OLT). A novel approach to treating the bleeding diathesis of patients with cirrhosis is administration of recombinant factor VIIa (rFVIIa). This study examined whether the efficacy of rFVIIa in cirrhosis might be explained in part by enhanced down-regulation of fibrinolysis by thrombin-activatable fibrinolysis inhibitor (TAFI). Addition of therapeutic or supratherapeutic doses of rFVIIa to plasma of 12 patients with stable cirrhosis did not result in a prolongation of clot lysis time, though clotting times were significantly reduced. Also, clot lysis assays of plasma samples taken during and after OLT, which was performed with or without a single bolus dose of rFVIIa, did not show any effect of rFVIIa on plasma fibrinolytic potential. In conclusion, this study shows no evidence for an antifibrinolytic effect of rFVIIa in cirrhotic patients or in patients undergoing OLT.
authors.affiliation: Thrombosis and Haemostasis Laboratory, Department of Haematology G.03.647, University Medical Center, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. j.a.lisman@lab.azu.nl
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.forename: Frank W G
authors.initials: FW
authors.lastname: Leebeek
authors.forename: Karina
authors.initials: K
authors.lastname: Meijer
authors.forename: Jan
authors.initials: J
authors.lastname: Van Der Meer
authors.forename: H Karel
authors.initials: HK
authors.lastname: Nieuwenhuis
authors.forename: Philip G
authors.initials: PG
authors.lastname: De Groot
mesh_terms: D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D025901:Carboxypeptidase B2 / Q000032:analysis / Q000502:physiology; D015942:Factor VIIa / Q000627:therapeutic use*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000601:surgery*; D016031:Liver Transplantation; D011516:Prothrombin / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000933:Antifibrinolytic Agents; D011994:Recombinant Proteins; D011516:Prothrombin; D025901:Carboxypeptidase B2; D015942:Factor VIIa