M Napolitano1, M N D Di Minno2, A Batorova3, A Dolce4, M Giansily-Blaizot5, J Ingerslev6, J-F Schved5, G Auerswald7, G Kenet8,9, M Karimi10, T Shamsi11, A Ruiz de Sáez12, R Dolatkhah13, A Chuansumrit14, M A Bertrand15, G Mariani16. 1. Haematology Unit, Thrombosis and Hemostasis Reference Regional Center, University of Palermo, Palermo, Italy. mariasanta.napolitano@unipa.it. 2. Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. 3. The National Haemophilia Centre, Institute of Haematology and Blood Transfusion, School of Medicine of Comenius University, University Hospital, Bratislava, Slovakia. 4. National Institute of Statistics, Palermo, Italy. 5. Laboratory of Haematology, University Hospital, Montpellier, France. 6. Centre for Haemophilia & Thrombosis, University Hospital Skejby, Aarhus, Denmark. 7. Klinikum Bremen-Mitte, Prof.-Hess Kinderklinik, Bremen, Germany. 8. National Hemophilia Center, Chaim Sheba Medical Center, Tel Hashomer, Israel. 9. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 10. Haematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 11. National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan. 12. Centro Nacional de Hemophilia, Banco Municipal de Sangre, Caracas, Venezuela. 13. Haematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 14. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 15. CRTH de Besançon, Besançon, France. 16. Westminster University, London, UK.
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.
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.