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Review article: Medical guidelines

Vol. 150 No. 5153 (2020)

Management of bleeding events and invasive procedures in patients with haemophilia A without inhibitors treated with emicizumab: A consensus statement of the Working Party on Haemostasis of the Swiss Society of Haematology and the Swiss Haemophilia Network

DOI
https://doi.org/10.4414/smw.2020.20422
Cite this as:
Swiss Med Wkly. 2020;150:w20422
Published
18.12.2020

Abstract

INTRODUCTION

Emicizumab (Hemlibra®, Hoffmann-La Roche, Switzerland) is now available for haemophilia A patients with or without factor VIII inhibitors. Management of bleeding events and replacement therapy for invasive procedures have to be adapted.

OBJECTIVE

To provide a practical guidance for the management of breakthrough bleeding events and elective or urgent surgery in adult and paediatric patients with haemophilia A without inhibitors treated with emicizumab.

METHODS

Based on the available literature and the experiences collected from adult and paediatric patients treated in Switzerland, the Working Party on Haemostasis of the Swiss Society of Haematology and the Swiss Haemophilia Network worked together to reach a consensus on the management of bleeding events and invasive procedures.

RESULTS AND CONCLUSION

Minor bleeding events and invasive procedures associated with low bleeding risk can be treated without factor replacement therapy in most cases, whereas major bleeding events and high-risk surgery require additional factor VIII replacement at usual doses, at least for the first days. Emicizumab treatment should be continued throughout the procedure and during the postoperative period. Elective major surgery should be planned according to emicizumab dosing for patients with a once-a-month posology. Of note, so far only few data are available on the management of major bleeds and surgery in patients with haemophilia A treated with emicizumab and this practical guidance will have to be regularly updated with growing experience.

References

  1. Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, et al. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018;379(9):811–22. doi:.https://doi.org/10.1056/NEJMoa1803550
  2. Pipe SW, Shima M, Lehle M, Shapiro A, Chebon S, Fukutake K, et al. Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study. Lancet Haematol. 2019;6(6):e295–305. doi:.https://doi.org/10.1016/S2352-3026(19)30054-7
  3. Castaman G, Santoro C, Coppola A, Mancuso ME, Santoro RC, Bernardini S, et al.; ad hoc Working Group. Emergency management in patients with haemophilia A and inhibitors on prophylaxis with emicizumab: AICE practical guidance in collaboration with SIBioC, SIMEU, SIMEUP, SIPMeL and SISET. Blood Transfus. 2020;18(2):143–51.
  4. Susen S, Gruel Y, Godier A, Harroche A, Chambost H, Lasne D, et al. Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra® ): Proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP). Haemophilia. 2019;25(5):731–7. doi:.https://doi.org/10.1111/hae.13817
  5. Collins PW, Liesner R, Makris M, Talks K, Chowdary P, Chalmers E, et al. Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee. Haemophilia. 2018;24(3):344–7. doi:.https://doi.org/10.1111/hae.13495
  6. Holstein K, Albisetti M, Bidlingmaier C, Halimeh S, Heine S, Klamroth R, et al.; ‘Ständige Kommission Hämophilie’ (Haemophilia board) of the German, Swiss Austrian Society for Thrombosis Haemostasis Research (GTH). Practical Guidance of the GTH Haemophilia Board on the Use of Emicizumab in Patients with Haemophilia A. Hamostaseologie. 2020. doi:.https://doi.org/10.1055/a-1127-6476
  7. Callaghan M, Trzaskoma B, Ko RH, Lee L, Patel AM, Tzeng E, et al. Factor VIII Use in the Treatment of Breakthrough Bleeds in Hemophilia A Patients without Inhibitors on Emicizumab Prophylaxis: The Phase 3 HAVEN 3 Study Experience. Blood. 2019;134(Supplement_1):2395. doi:.https://doi.org/10.1182/blood-2019-123654
  8. Paz-Priel I, Chang T, Asikanius E, Chebon S, Emrich T, Fernandez E, et al. Immunogenicity of Emicizumab in People with Hemophilia A (PwHA): Results from the HAVEN 1-4 Studies. Blood. 2018;132(Supplement 1):633. doi:.https://doi.org/10.1182/blood-2018-99-118492
  9. Valsecchi C, Gobbi M, Schiavone L, Beeg M, Adams PE, Mancuso ME, et al. Characterization of Neutralizing Anti-emicizumab Antibody Developed in a Hemophilia A Patient. ISTH 2020 Virtual Congress. 2020. Abstract PB1159.
  10. Adamkewicz JI, Chen DC, Paz-Priel I. Effects and Interferences of Emicizumab, a Humanised Bispecific Antibody Mimicking Activated Factor VIII Cofactor Function, on Coagulation Assays. Thromb Haemost. 2019;119(7):1084–93. doi:.https://doi.org/10.1055/s-0039-1688687
  11. Tripodi A, Santoro RC, Testa S, Molinari AC, Bernardini S, Golato M, et al. Position paper on laboratory testing for patients with haemophilia. A consensus document from SISET, AICE, SIBioC and SIPMeL. Blood Transfus. 2019;17(3):229–36.
  12. Tripodi A, Chantarangkul V, Novembrino C, Scalambrino E, Boscolo-Anzoletti M, Clerici M, et al. Emicizumab, the factor VIII mimetic bi-specific monoclonal antibody and its measurement in plasma. Clin Chem Lab Med. 2020;/j/cclm.ahead-of-print/cclm-2020-0696/cclm-2020-0696.xml.
  13. Müller J, Pekrul I, Pötzsch B, Berning B, Oldenburg J, Spannagl M. Laboratory Monitoring in Emicizumab-Treated Persons with Hemophilia A. Thromb Haemost. 2019;119(9):1384–93. doi:.https://doi.org/10.1055/s-0039-1692427
  14. Schulman S, Kearon C ; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692–4. doi:.https://doi.org/10.1111/j.1538-7836.2005.01204.x
  15. Santagostino E, Oldenburg J, Chang T, Xu J, Chebon S, Doral M, et al. Surgical Experience from Four Phase III Studies (HAVEN 1- 4) of Emicizumab in Persons with Haemophilia A (PwHA) with or without FVIII Inhibitors. Res Pract Thromb Haemost. 2019;3:115.
  16. Ebbert PT, Xavier F, Seaman CD, Ragni MV. Emicizumab prophylaxis in patients with haemophilia A with and without inhibitors. Haemophilia. 2020;26(1):41–6. doi:.https://doi.org/10.1111/hae.13877
  17. McCary I, Guelcher C, Kuhn J, Butler R, Massey G, Guerrera MF, et al. Real-world use of emicizumab in patients with haemophilia A: Bleeding outcomes and surgical procedures. Haemophilia. 2020;26(4):631–6. doi:.https://doi.org/10.1111/hae.14005
  18. Lewandowska M, Randall N, Maahs J, Bakeer J, Sagar J, Greist A, et al. Real-World Experience with Emicizumab in Persons with Hemophilia A (HA) with or without Inhibitors. ISTH 2020 Virtual Congress. 2020. Abstract PB0928.
  19. Boehlen F, Burkhard PR, Momjian S, Fontana P. Subthalamic nucleus deep brain stimulation for Parkinson’s disease in a patient with severe haemophilia A. Haemophilia. 2017;23(3):e246–8. doi:.https://doi.org/10.1111/hae.13235
  20. 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(1):e19–25. doi:.https://doi.org/10.1111/hae.12530
  21. Hermans C, Apte S, Santagostino E. Invasive procedures in patients with haemophilia: Review of low-dose protocols and experience with extended half-life FVIII and FIX concentrates and non-replacement therapies. Haemophilia. 2020;hae.13978. doi:.https://doi.org/10.1111/hae.13978
  22. Bravo MI, Raventós A, Pérez A, Costa M, Willis T. Non-additive effect on thrombin generation when a plasma-derived factor VIII/von Willebrand factor (FVIII/VWF) is combined with emicizumab in vitro. J Thromb Haemost. 2020;18(8):1934–9. doi:.https://doi.org/10.1111/jth.14887
  23. Kitazawa T, Esaki K, Tachibana T, Ishii S, Soeda T, Muto A, et al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017;117(7):1348–57. doi:.https://doi.org/10.1160/TH17-01-0030
  24. Fernandez-Bello I, Alvarez-Roman M, Martin-Salces M, Rivas-Pollmat I, et al. Thromboelastometry may be useful to guide treatment for breakthrough and perioperative bleeds of patients on prophylaxis with emicizumab. Haemophilia. 2019;25:106.

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