title: Recombinant activated factor VII in the treatment of bleeds and for the prevention of surgery-related bleeding in congenital haemophilia with inhibitors.
abstract: The availability of recombinant activated factor VII (rFVIIa, eptacog alfa activated) has greatly advanced the care of patients with haemophilia A or B who have developed inhibitors against the infused replacement factor. Recombinant FVIIa is licensed for the on-demand treatment of bleeding episodes and the prevention of bleeding in surgery or invasive procedures in patients with congenital haemophilia with inhibitors. This article attempts to review in detail the extensive evidence of rFVIIa in congenital haemophilia patients with inhibitors. Patients with acute bleeding episodes are best treated on demand at home, to achieve the short- and long-term benefits of rapid bleed control. Key prospective studies have shown that rFVIIa achieves consistently high efficacy rates in the management of acute (including joint) bleeds in inhibitor patients in the home treatment setting. Substantial post-approval data from key registries also support the on-demand efficacy profile of rFVIIa established by the prospective clinical trials. The availability of rFVIIa has allowed major surgery to become a reality for inhibitor patients. Studies in key surgery, including orthopaedic procedures, have found that rFVIIa provides consistently high efficacy rates. Importantly, the wealth of data does not raise any unexpected safety concerns surrounding rFVIIa use; this is likely because rFVIIa is a recombinant product with a localised mechanism of action at the site of vascular injury. In summary, rFVIIa is established as an effective and well-tolerated first-line treatment for on-demand bleeding control and bleed prevention during minor and major (including elective orthopaedic) surgery in inhibitor patients. Use of rFVIIa has been a major step towards narrowing the gap in outcomes between inhibitor patients and non-inhibitor patients.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Cà Granda Foundation Maggiore Policlinico Hospital, Milan, Italy. Electronic address: Hemophilia_ctr@policlinico.mi.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.affiliation: Gulf States Hemophilia and Thrombophilia Center, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Escobar
authors.affiliation: IHTC, Cláudio L.P. Correa, Hemocentro Unicamp, INCT do Sangue, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Margareth
authors.initials: M
authors.lastname: Ozelo
authors.affiliation: Ortho-trauma Unit, Emergency Department, IRCCS Cà Granda Foundation Maggiore Policlinico Hospital, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Solimeno
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Arkhammar
authors.affiliation: Novo Nordisk Health Care AG, Zürich, Switzerland.
authors.forename: Hye Youn
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Novo Nordisk Health Care AG, Zürich, Switzerland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rosu
authors.affiliation: Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Giangrande
mesh_terms: D016063:Blood Loss, Surgical / Q000517:prevention & control*; D015942:Factor VIIa / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: Congenital haemophilia with inhibitors; On-demand treatment; Recombinant activated factor VII; Surgery