title: Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies.
abstract: BACKGROUND
  A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency.
  
  
  OBJECTIVE
  Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences.
  
  
  METHODS
  A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed.
  
  
  RESULTS
  In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 μg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 μg kg(-1) (divided as three doses).
  
  
  CONCLUSIONS
  Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies.
authors.affiliation: Haematology Unit, Thrombosis and Hemostasis Reference Regional Center, University of Palermo, Palermo, Italy. mariasanta.napolitano@unipa.it.
authors.forename: M
authors.initials: M
authors.lastname: Napolitano
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: M N D
authors.initials: MN
authors.lastname: Di Minno
authors.affiliation: The National Haemophilia Centre, Institute of Haematology and Blood Transfusion, School of Medicine of Comenius University, University Hospital, Bratislava, Slovakia.
authors.forename: A
authors.initials: A
authors.lastname: Batorova
authors.affiliation: National Institute of Statistics, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Dolce
authors.affiliation: Laboratory of Haematology, University Hospital, Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Giansily-Blaizot
authors.affiliation: Centre for Haemophilia & Thrombosis, University Hospital Skejby, Aarhus, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Ingerslev
authors.affiliation: Laboratory of Haematology, University Hospital, Montpellier, France.
authors.forename: J-F
authors.initials: JF
authors.lastname: Schved
authors.affiliation: Klinikum Bremen-Mitte, Prof.-Hess Kinderklinik, Bremen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Auerswald
authors.affiliation: National Hemophilia Center, Chaim Sheba Medical Center, Tel Hashomer, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Kenet
authors.affiliation: Haematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Karimi
authors.affiliation: National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan.
authors.forename: T
authors.initials: T
authors.lastname: Shamsi
authors.affiliation: Centro Nacional de Hemophilia, Banco Municipal de Sangre, Caracas, Venezuela.
authors.forename: A
authors.initials: A
authors.lastname: Ruiz de Sáez
authors.affiliation: Haematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: R
authors.initials: R
authors.lastname: Dolatkhah
authors.affiliation: Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: A
authors.initials: A
authors.lastname: Chuansumrit
authors.affiliation: CRTH de Besançon, Besançon, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Bertrand
authors.affiliation: Westminster University, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Mariani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003029:Coagulants / Q000627:therapeutic use*; D015331:Cohort Studies; D005167:Factor VII / Q000032:analysis; D005168:Factor VII Deficiency / Q000188:drug therapy*; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007223:Infant; D008297:Male; D008595:Menorrhagia / Q000453:epidemiology; D008875:Middle Aged; D010641:Phenotype; D016016:Proportional Hazards Models; D012372:ROC Curve; D011994:Recombinant Proteins / Q000627:therapeutic use; D012042:Registries; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000933:Antifibrinolytic Agents; D003029:Coagulants; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: gynaecological bleeding; inherited factor VII deficiency; recombinant activated factor VII; women