International Journal of Hematology

, Volume 95, Issue 1, pp 57–63 | Cite as

Recombinant activated factor VII (rFVIIa/NovoSeven®) in the management of severe postpartum haemorrhage: initial report of a multicentre case series in Japan

  • Takao Kobayashi
  • Masao Nakabayashi
  • Akira Yoshioka
  • Makoto Maeda
  • Tsuyomu Ikenoue
Original Article


Only a limited number of case reports documenting the off-label use of recombinant factor VIIa (rFVIIa) in Japanese patients with postpartum haemorrhage (PPH) have been published. Data on Japanese cases with severe PPH in which rFVIIa was administered were collected. Data of obstetric haemorrhage patients treated with rFVIIa between 2005 and 2010 were retrospectively collected throughout Japan. The data included patients’ background information, blood product requirements, dose/timing of rFVIIa, and adverse effects. Treating clinicians subjectively assessed the effect of rFVIIa on bleeding at each administration using four categories: “Stopped”, “Decreased”, “Unchanged”, and “Increased”. A total of 25 women received rFVIIa for the treatment of obstetric haemorrhage in 18 institutions. After the final administration, bleeding was “stopped” in 16 patients (64%), “decreased” in eight patients (32%), and “unchanged” in one patient (4%). A significant reduction in blood product requirement was observed following the first rFVIIa administration. Hysterectomy was required in two patients (15.4%) after rFVIIa administration. Four asymptomatic thrombotic events were reported in three patients. These results suggest that rFVIIa can be a beneficial therapeutic option that can reduce blood loss and prevent hysterectomy in Japanese patients with massive obstetric bleeding.


Hysterectomy Postpartum haemorrhage Recombinant activated factor VII 


  1. 1.
    Ministry of Health, Labour and Welfare. Vital statistics of Japan: number of maternal deaths and death rates by selected causes (1980, 1985, 1988–2009).Google Scholar
  2. 2.
    Martinowitz U, Michaelson M, Israeli Multidisciplinary rFVIIa Task Force. Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force. J Thromb Haemost. 2005;3:640–8.Google Scholar
  3. 3.
    Lusher JM. Recombinant factor VIIa (Novoseven) in the treatment of internal bleeding in patients with factor VIII and IX inhibitors. Haemostasis. 1996;26:124–30.PubMedGoogle Scholar
  4. 4.
    Lisman T, Adelmeijer J, Cauwenberghs S, van Pampus ECM, Heemkerk JWN, de Groot PG. Recombinant factor VIIa enhances platelet adhesion and activation under flow conditions at normal and reduced platelet count. J Thromb Haemost. 2005;3:742–51.PubMedCrossRefGoogle Scholar
  5. 5.
    Mittal S, Watson HG. A critical appraisal of the use of recombinant factor VIIa in acquired bleeding conditions. Br J Haematol. 2006;133:355–63.PubMedCrossRefGoogle Scholar
  6. 6.
    Aggarwal A, Malkovska V, Catlett JP, Alcorn K. Recombinant activated factor VII (rFVIIa) as salvage treatment for intractable hemorrhage. Thromb J. 2004;2:9.PubMedCrossRefGoogle Scholar
  7. 7.
    Hamaekers AEW, van Mook WNKA, Offermans JPM, Marcus MAE. Successful use of recombinant factor VIIa for treatment of severe postpartum hemorrhage. Am J Crit Care. 2006;15:399–401.PubMedGoogle Scholar
  8. 8.
    Mechsner S, Baessler K, Brunne B, Albrecht T, Hopp H, Dudenhausen JW. Using recombinant activated factor VII, B-Lynch compression, and reversible embolization of the uterine arteries for treatment of severe conservatively intractable postpartum hemorrhage: new method for management of massive hemorrhage in cases of placenta increta. Fertil Steril. 2008;90(5):2012.e1–5.Google Scholar
  9. 9.
    Tanchev S, Platikanov V, Karadimov D. Administration of recombinant factor VIIa for the management of massive bleeding due to uterine atonia in the post-placental period. Acta Obstet Gynecol Scand. 2005;84:402–3.PubMedGoogle Scholar
  10. 10.
    Boehlen F, Morales MA, Fontana P, Ricou B, Irion O, de Moerloose P. Prolonged treatment of massive postpartum haemorrhage with recombinant factor VIIa: case report and review of the literature. Br J Obstet Gynaecol. 2004;111:284–7.CrossRefGoogle Scholar
  11. 11.
    Price G, Kaplan J, Skowronski G. Use of recombinant factor VIIa to treat life-threatening non-surgical bleeding in a post-partum patient. Br J Anaesth. 2004;93:298–300.PubMedCrossRefGoogle Scholar
  12. 12.
    Ahonen J, Jokela R. Recombinant factor VIIa for life-threatening post-partum haemorrhage. Br J Anaesth. 2005;94:592–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Nohira T, Osakabe Y, Suda S, Takahashi C, Tanaka A, Ikeda K, et al. Successful management by recombinant activated factor VIIa in a case of disseminated intravascular coagulopathy caused by obstetric hemorrhage. J Obstet Gynaecol Res. 2008;34:623–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Phillips LE, McLintock C, Pollock W, Gatt S, Popham P, Jankelowitz G, et al. Recombinant activated factor VII in obstetric hemorrhage: experiences from the Australian and New Zealand Haemostasis Registry. Anesth Analg. 2009;109:1908–15.PubMedCrossRefGoogle Scholar
  15. 15.
    Welsh A, McLintock C, Gatt S, Somerset D, Popham P, Ogle R. Guidelines for the use of recombinant activated factor VII in massive obstetric haemorrhage. Aust N Z J Obstet Gynaecol. 2008;48:12–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Grounds RM, Seebach C, Knothe C, Paluszkiewicz P, Smith T, Kasal E, et al. Use of recombinant activated factor VII (Novoseven) in trauma and surgery: analysis of outcomes reported to an International Registry. J Intensive Care Med. 2006;21:27–39.PubMedCrossRefGoogle Scholar
  17. 17.
    Dunkley S, Phillips L, McCall P, Brereton J, Lindeman R, Jankelowitz G, et al. Recombinant activated factor VII in cardiac surgery: experience from the Australian and New Zealand Haemostasis Registry. Ann Thorac Surg. 2008;85(3):836–44.PubMedCrossRefGoogle Scholar
  18. 18.
    Knudson MM, Cohen MJ, Reidy R, Jaeger S, Bacchetti P, Jin C, et al. Trauma, transfusions, and use of recombinant factor VIIa: a multicenter case registry report of 380 patients from the Western Trauma Association. J Am Coll Surg. 2011;212(1):87–95.PubMedCrossRefGoogle Scholar
  19. 19.
    Cameron P, Phillips L, Balogh Z, Joseph A, Pearce A, Parr M, et al. The use of recombinant activated factor VII in trauma patients: experience from the Australian and New Zealand haemostasis registry. Injury. 2007;38:1030–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Hoffman M. A cell-based model of coagulation and the role of factor VIIa. Blood Rev. 2003;17:S1–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Biss TT, Hanley JP. Recombinant activated factor VII (rFVIIa/NovoSeven®) in intractable haemorrhage: use of a clinical scoring system to predict outcome. Vox Sang. 2006;90:45–52.PubMedCrossRefGoogle Scholar
  22. 22.
    Alfirevic Z, Elbourne D, Pavord S, Bolte A, Van Geijn H, Mercier F, et al. Use of recombinant activated factor VII in primary postpartum hemorrhage: the Northern European registry 2000–2004. Obstet Gynecol. 2007;110:1270–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Bomken C, Mathai S, Biss T, Loughney A, Hanley J. Recombinant activated factor VII (rFVIIa) in the management of major obstetric haemorrhage: a case series and a proposed guideline for use. Obstet Gynecol Int. 2009;2009:364843.PubMedGoogle Scholar
  24. 24.
    Bouma LS, Bolte AC, van Geijn HP. Use of recombinant activated factor VII in massive postpartum haemorrhage. Eur J Obstet Gynecol Reprod Biol. 2008;137:172–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Habek D, Becarevic R. Emergency peripartum hysterectomy in a tertiary obstetric center: 8-year evaluation. Fetal Diagn Ther. 2007;22:139–42.PubMedCrossRefGoogle Scholar
  26. 26.
    Shirahata A, Kamiya T, Takamatsu J, Kojima T, Fukutake K, Arai M, et al. Clinical trial to investigate the pharmacokinetics, pharmacodynamics, safety, and efficacy of recombinant factor VIIa in Japanese patients with hemophilia with inhibitors. Int J Hematol. 2001;73:517–25.PubMedCrossRefGoogle Scholar
  27. 27.
    Albrecht J, Meves A, BIgby M. Case reports and case series from Lancet had significant impact on medical literature. J Clin Epidemiol. 2005;58:1227–32.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2011

Authors and Affiliations

  • Takao Kobayashi
    • 1
  • Masao Nakabayashi
    • 2
  • Akira Yoshioka
    • 3
  • Makoto Maeda
    • 4
  • Tsuyomu Ikenoue
    • 5
  1. 1.Hamamatsu Medical CenterHamamatsuJapan
  2. 2.Aiiku Maternal and Child Health CenterTokyoJapan
  3. 3.Nara Medical UniversityKashiharaJapan
  4. 4.Department of Obstetrics and GynecologyMie Chuo Medical CenterTsuJapan
  5. 5.University of Miyazaki HospitalMiyazakiJapan

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