Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies

Haemophilia. 2016 Sep;22(5):752-9. doi: 10.1111/hae.12978. Epub 2016 Jun 24.

Abstract

Introduction: A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency.

Aim: 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).

Conclusion: 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.

Keywords: gynaecological bleeding; inherited factor VII deficiency; recombinant activated factor VII; women.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antifibrinolytic Agents / therapeutic use
  • Child
  • Child, Preschool
  • Coagulants / therapeutic use*
  • Cohort Studies
  • Factor VII / analysis
  • Factor VII Deficiency / drug therapy*
  • Factor VIIa / therapeutic use*
  • Female
  • Hemorrhage / epidemiology
  • Hemorrhage / prevention & control
  • Humans
  • Infant
  • Male
  • Menorrhagia / epidemiology
  • Middle Aged
  • Phenotype
  • Proportional Hazards Models
  • ROC Curve
  • Recombinant Proteins / therapeutic use
  • Registries
  • Treatment Outcome
  • Young Adult

Substances

  • Antifibrinolytic Agents
  • Coagulants
  • Recombinant Proteins
  • Factor VII
  • recombinant FVIIa
  • Factor VIIa