Abstract
FEIBA(®) consists of zymogens and traces of activated forms of procoagulant factors II, VII, IX, X, anticoagulants protein C and TFPI, and small amounts of cofactors FV, FVIII and protein S, in a balanced ratio. As shown previously, FII-FXa complex plays a key role in FEIBA's mode of action (MoA). Thrombin generation (TG) was measured by spiking coagulation factors, cofactors and inhibitors to high titer FVIII inhibitor plasma, and in plasma samples from patients in a phase 3 clinical study evaluating the safety and efficacy of FEIBA prophylaxis in haemophilia A patients with inhibitors. Increasing the FXa/FII ratio improved TG, while adding coagulation enzyme components had a negligible effect. Adding FX, FIX, and FVII increased the peak thrombin and decreased the lag time. The presence of FV and phospholipids led to faster TG, while protein C and protein S reduced the amount of peak thrombin. TFPI appeared to have no effect. Patients on prophylaxis with FEIBA(®) showed higher peak thrombin and AUC with elevated FII, FX, FIX, FVIIa, and protein C levels, and experienced significantly less bleeding episodes than those receiving on-demand treatment. These experiments showed that although the FII-FXa complex induced immediate thr...Continue Reading
References
Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·B Osterud, S I Rapaport
Oct 1, 1979·The Journal of Clinical Investigation·U SeligsohnS I Rapaport
Nov 1, 1977·Thrombosis Research·F E PrestonJ F Hamlyn
Sep 2, 1991·Science·D Gailani, G J Broze
Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D RepkeY Nemerson
May 25, 1990·Journal of Immunological Methods·W L Naser
Jan 1, 1996·Seminars in Thrombosis and Hemostasis·F A OfosuJ Freedman
Jun 15, 1997·Thrombosis Research·P HellsternB Faller-Stöckl
Mar 28, 1998·Biochemistry·F A Baglia, P N Walsh
Jan 5, 1999·Haemophilia : the Official Journal of the World Federation of Hemophilia·H R RobertsM Hoffman
Oct 26, 1999·Vox Sanguinis·P L TurecekH P Schwarz
Jul 11, 2003·Pathophysiology of Haemostasis and Thrombosis·P L TurecekH P Schwarz
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·N BrufattoM E Nesheim
Nov 25, 2003·Journal of Thrombosis and Haemostasis : JTH·K VáradiP L Turecek
Sep 24, 2004·Haemophilia : the Official Journal of the World Federation of Hemophilia·P L TurecekH P Schwarz
Sep 23, 2006·Blood·Jan AstermarkUNKNOWN FENOC Study Group
Oct 27, 2007·Haemophilia : the Official Journal of the World Federation of Hemophilia·L M Aledort
Aug 13, 2008·Blood·Connie DuckersElisabetta Castoldi
Nov 3, 2009·Haemophilia : the Official Journal of the World Federation of Hemophilia·C Escuriola Ettingshausen, W Kreuz
Nov 13, 2010·Haemophilia : the Official Journal of the World Federation of Hemophilia·B Tardy-PoncetB Tardy
Mar 1, 1992·Trends in Cardiovascular Medicine·G J Broze
Nov 4, 2011·The New England Journal of Medicine·Cindy LeissingerLorenzo Mantovani
May 29, 2012·Journal of Thrombosis and Haemostasis : JTH·M Hoffman, Y Dargaud
Aug 6, 2013·Haemophilia : the Official Journal of the World Federation of Hemophilia·S V AntunesW-Y Wong
Apr 2, 2014·International Journal of Hematology·Kenichi OgiwaraMidori Shima
Jan 22, 2015·Haemophilia : the Official Journal of the World Federation of Hemophilia·N EwingW Kreuz
Feb 5, 2015·International Journal of Laboratory Hematology·B ShenkmanU Martinowitz
Citations
Apr 13, 2018·Journal of Thrombosis and Haemostasis : JTH·Keiji NogamiMidori Shima
Jun 12, 2018·Journal of Thrombosis and Haemostasis : JTH·R HartmannF Scheiflinger
Feb 6, 2019·VASA. Zeitschrift für Gefässkrankheiten·Paul Gressenberger
Jan 4, 2018·Blood Advances·Matteo RotaLorenzo G Mantovani
Oct 12, 2018·International Journal of Hematology·Pratima Chowdary
Sep 26, 2017·The Cochrane Database of Systematic Reviews·Chatree Chai-AdisaksophaBarbara A Konkle
Sep 12, 2020·Hämostaseologie·Andreas Tiede
Oct 29, 2017·Journal of Thrombosis and Haemostasis : JTH·J D BeckmanA S Wolberg
Aug 5, 2017·Haemophilia : the Official Journal of the World Federation of Hemophilia·S FurukawaM Shima
Jan 19, 2018·Nature Reviews. Cardiology·Jerrold H LevyJeffrey I Weitz
May 31, 2018·Drugs·Pratima Chowdary
Jul 28, 2020·Hämostaseologie·Hans H BrackmannClaude Négrier
May 11, 2020·Blood Cells, Molecules & Diseases·Puja SoniShrimati Shetty
Apr 6, 2021·Journal of Thrombosis and Haemostasis : JTH·Marianne KjalkeIda Hilden
May 27, 2021·Journal of Cardiothoracic and Vascular Anesthesia·Christian O'DonnellCharles C Hill
Aug 19, 2021·The Cochrane Database of Systematic Reviews·Omotola O OlasupoDavide Matino
Sep 16, 2021·Journal of Thrombosis and Haemostasis : JTH·François DepassePeter L Turecek