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Continuous infusions of B domain-truncated recombinant factor VIII, turoctocog alfa, for orthopedic surgery in severe hemophilia A: first case report

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Abstract

Continuous infusions (CI) of factor (F)VIII are preferable to the conventional bolus injections for the maintenance of consistent FVIII levels during surgery in patients with severe hemophilia A. A third generation, B domain-truncated recombinant FVIII (turoctocog alfa, Novo Nordisk, NovoEight®), was approved for clinical use in 2014. The hemostatic efficacy and safety of bolus injections of turoctocog alfa in patients undergoing surgery have been reported, but no reports on CI therapy have been published. We describe a 43-year-old patient with severe hemophilia A who required arthroscopic synovectomy of the right elbow and arthrodesis of the right ankle. He was treated with a bolus injection of turoctocog alfa (36 IU/kg) immediately before operation, followed by CI (infusion rate; 2.9 IU/kg/h) to maintain FVIII activity > 80 IU/dl throughout the perioperative period. Surgery was completed successfully with uncomplicated hemostatic control. CIs were continued until post-operative day (POD) 4. Further bolus injections were given from POD5. No anti-FVIII inhibitor has been detected post-operation. This case provides important information on CI therapy using turoctocog alfa during surgery for patients with severe hemophilia A.

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References

  1. Mannucci PM, Tuddenham EG. The hemophilias–from royal genes to gene therapy. N Engl J Med. 2001;344:1773–9.

    Article  PubMed  CAS  Google Scholar 

  2. Santagostino E, Lentz SR, Misgav M, Brand B, Chowdary P, Savic A, et al. Safety and efficacy of turoctocog alfa (NovoEight(R)) during surgery in patients with haemophilia A: results from the multinational guardian clinical trials. Haemophilia. 2015;21:34–40.

    Article  PubMed  CAS  Google Scholar 

  3. Björkman S, Berntorp E. Pharmacokinetics of coagulation factors: clinical relevance for patients with haemophilia. Clin Pharmacokinet. 2001;40:815–32.

    Article  PubMed  Google Scholar 

  4. Fay PJ. Activation of factor VIII and mechanisms of cofactor action. Blood Rev. 2004;18:1–15.

    Article  PubMed  Google Scholar 

  5. Pipe SW. Functional roles of the factor VIII B domain. Haemophilia. 2009;15:1187–96.

    Article  PubMed  CAS  Google Scholar 

  6. Grushin K, Miller J, Dalm D, Parker ET, Healey JF, Lollar P, et al. Lack of recombinant factor VIII B-domain induces phospholipid vesicle aggregation: implications for the immunogenicity of factor VIII. Haemophilia. 2014;20:723–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Lentz SR, Misgav M, Ozelo M, Salek SZ, Veljkovic D, Recht M, et al. Results from a large multinational clinical trial (guardian1) using prophylactic treatment with turoctocog alfa in adolescent and adult patients with severe haemophilia A: safety and efficacy. Haemophilia. 2013;19:691–7.

    Article  PubMed  CAS  Google Scholar 

  8. Lentz SR, Cerqueira M, Janic D, Kempton C, Matytsina I, Misgav M, et al. Interim results from a large multinational extension trial (guardian 2) using turoctocog alfa for prophylaxis and treatment of bleeding in patients with severe haemophilia A. Haemophilia. 2016;22:e445–9.

    Article  PubMed  CAS  Google Scholar 

  9. Kulkarni R, Karim FA, Glamocanin S, Janic D, Vdovin V, Ozelo M, et al. Results from a large multinational clinical trial (guardian 3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A: safety, efficacy and pharmacokinetics. Haemophilia. 2013;19:698–705.

    Article  PubMed  CAS  Google Scholar 

  10. Meijer K, Rauchensteiner S, Santagostino E, Platokouki H, Schutgens RE, Brunn M, et al. Continuous infusion of recombinant factor VIII formulated with sucrose in surgery: non-interventional, observational study in patients with severe haemophilia A. Haemophilia. 2015;21:e19–25.

    Article  PubMed  CAS  Google Scholar 

  11. Windyga J, Rusen L, Gruppo R, O’Brien AC, Kelly P, Roth DA, et al. BDDrFVIII (Moroctocog alfa [AF-CC]) for surgical haemostasis in patients with haemophilia A: results of a pivotal study. Haemophilia. 2010;16:731–9.

    Article  PubMed  CAS  Google Scholar 

  12. Sennett MM, de Alarcon PA. Successful use of ReFacto continuous infusion in two paediatric patients with severe haemophilia A undergoing orthopaedic surgery. Haemophilia. 2004;10:655–60.

    Article  PubMed  CAS  Google Scholar 

  13. Stieltjes N, Altisent C, Auerswald G, Negrier C, Pouzol P, Reynaud J, et al. Continuous infusion of B-domain deleted recombinant factor VIII (ReFacto) in patients with haemophilia A undergoing surgery: clinical experience. Haemophilia. 2004;10:452–8.

    Article  PubMed  CAS  Google Scholar 

  14. Skands ARH, Engelund DK, Rossmeisl CC, Sejling K. Stability of turoctocog alfa, a new rFVIII product from Novo Nordisk, when stored at hight temperature and humidity. Haemophilia. 2014;20:176.

    Article  CAS  Google Scholar 

  15. Santagostino E. A new recombinant factor VIII: from genetics to clinical use. Drug Des Dev Ther. 2014;8:2507–15.

    Article  CAS  Google Scholar 

  16. Leyte A, van Schijndel HB, Niehrs C, Huttner WB, Verbeet MP, Mertens K, et al. Sulfation of Tyr1680 of human blood coagulation factor VIII is essential for the interaction of factor VIII with von Willebrand factor. J Biol Chem. 1991;266:740–6.

    PubMed  CAS  Google Scholar 

  17. Fay PJ, Coumans JV, Walker FJ. von Willebrand factor mediates protection of factor VIII from activated protein C-catalyzed inactivation. J Biol Chem. 1991;266:2172–7.

    PubMed  CAS  Google Scholar 

  18. Nogami K, Shima M, Nishiya K, Hosokawa K, Saenko EL, Sakurai Y, et al. A novel mechanism of factor VIII protection by von Willebrand factor from activated protein C-catalyzed inactivation. Blood. 2002;99:3993–8.

    Article  PubMed  CAS  Google Scholar 

  19. Grancha S, Navajas R, Maranon C, Paradela A, Albar JP, Jorquera JI. Incomplete tyrosine 1680 sulphation in recombinant FVIII concentrates. Haemophilia. 2011;17:709–10.

    Article  PubMed  CAS  Google Scholar 

  20. Nielsen PF, Bak S, Vandahl B. Characterization of tyrosine sulphation in rFVIII (turoctocog alfa) expressed in CHO and HEK-293 cells. Haemophilia. 2012;18:e397–8.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We would like to thank for Drs. Yasuaki Shida and Koji Yada for the clinical support.

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Authors and Affiliations

  1. Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

    Masahiro Takeyama, Keiji Nogami, Ryohei Kobayashi, Kenichi Ogiwara & Midori Shima

  2. Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan

    Akira Taniguchi, Yasuaki Nakanishi, Yusuke Inagaki & Yasuhito Tanaka

Authors
  1. Masahiro Takeyama
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  2. Keiji Nogami
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  3. Ryohei Kobayashi
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  4. Kenichi Ogiwara
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  5. Akira Taniguchi
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  6. Yasuaki Nakanishi
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  7. Yusuke Inagaki
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  8. Yasuhito Tanaka
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  9. Midori Shima
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Contributions

TM designed the research, analyzed the data, and drafted initial manuscript; NK interpreted the data, revised the manuscript, and approved the final version to be published; OK, KR, TA, NY, IY, and TY provided clinical support; SM supervised the manuscript.

Corresponding author

Correspondence to Keiji Nogami.

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Conflict of interest

Takeyama M, Ogiwara K, Inagaki Y, and Tanaka Y have received funding for their research from Novo Nordisk. Nogami K has received funding for his research from Novo Nordisk, Bayer, Shire, Bioverative, Chugai, and KAKETSUKEN. Shima M has received funding for his research from Novo Nordisk, Bayer, Shire, Pfizer, Bioverative, Chugai, and KAKETSUKEN. Kobayashi R, Taniguchi A, and Nakanishi Y have no conflicts of interest.

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Takeyama, M., Nogami, K., Kobayashi, R. et al. Continuous infusions of B domain-truncated recombinant factor VIII, turoctocog alfa, for orthopedic surgery in severe hemophilia A: first case report. Int J Hematol 108, 199–202 (2018). https://doi.org/10.1007/s12185-018-2415-5

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  • DOI: https://doi.org/10.1007/s12185-018-2415-5

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