Reviews
Vol. 4 No. 1 (2025)
The changing landscape of treatment for acquired hemophilia A
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: 8 October 2024
Accepted: 20 January 2025
Accepted: 20 January 2025
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Acquired hemophilia A (AHA) is a rare acquired autoimmune disorder caused by autoantibodies against coagulation factor VIII (FVIII), which cause a hemorrhagic diathesis, not rarely of severe degree. Standard treatment consists of bleeding control with bypassing agents (recombinant activated factor VII and activated prothrombin complex concentrate) and recombinant porcine FVIII, and immunosuppressive therapy (corticosteroids with or without cyclophosphamide). Recent studies have renewed the interest towards the immunosuppressive agent rituximab for FVIII inhibitor eradication and have suggested a potential role for emicizumab for the prevention of bleeding in AHA patients. This narrative review will focus on the placement of these two emerging drugs within the treatment landscape for AHA.
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Citations
1. Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol 2003;121:21-35. DOI: https://doi.org/10.1046/j.1365-2141.2003.04162.x
2. Franchini M, Lippi G. Acquired factor VIII inhibitors. Blood 2008;112:250-5. DOI: https://doi.org/10.1182/blood-2008-03-143586
3. Coppola A, Favaloro EJ, Tufano A, et al. Acquired inhibitors of coagulation factors: part I – acquired hemophilia A. Semin Thromb Hemost 2012;38:433-46. DOI: https://doi.org/10.1055/s-0032-1315757
4. Franchini M, Mannucci PM. Acquired haemophilia A: a 2013 update. Thromb Haemost 2013;110:1114-20. DOI: https://doi.org/10.1160/TH13-05-0363
5. Coppola A, Franchini M, Tripodi A, et al; ad hoc Working Group. Acquired haemophilia A: Italian Consensus Recommendations on diagnosis, general management and treatment of bleeding. Blood Transfus 2022;20:245-62.
6. Collins PW, Hirsch S, Baglin TP, et al. Acquired haemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors’ Organisation. Blood 2007;109:1870-7. DOI: https://doi.org/10.1182/blood-2006-06-029850
7. Knoebl P, Marco P, Baudo F, et al; on behalf of the EACH2 Registry Contributors. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost 2012;10:622-31. DOI: https://doi.org/10.1111/j.1538-7836.2012.04654.x
8. Kessler CM, Ma AD, Al-Mondhiry HA, Gut RZ, Cooper DL. Assessment of acquired hemophilia patient demographics in the United States: the Hemostasis and Thrombosis Research Society Registry. Blood Coagul Fibrinolysis 2016;27:761-9. DOI: https://doi.org/10.1097/MBC.0000000000000582
9. Franchini M, Schiavulli M, Liumbruno GM. Hemostatic therapy as a management strategy for acquired hemophilia: what does the future hold? Expert Rev Hematol 2021;14:263-70. DOI: https://doi.org/10.1080/17474086.2021.1892483
10. Tiede A, Collins P, Knoebl P, et al. International recommendations on the diagnosis and treatment of acquired hemophilia A. Haematologica 2020;105:1791-801. DOI: https://doi.org/10.3324/haematol.2019.230771
11. Franchini M, Focosi D. Inhibitor eradication and treatment for acquired hemophilia A. Expert Rev Hematol 2024;17:233-240. DOI: https://doi.org/10.1080/17474086.2024.2352505
12. Collins P, Baudo F, Knoebl P, et al.; EACH2 registry collaborators. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). Blood 2012;120:47-55. DOI: https://doi.org/10.1182/blood-2012-02-409185
13. Franchini M, Lippi G. Recombinant activated factor VII: mechanisms of action and current indications. Semin Thromb Hemost 2010;36:485-92. DOI: https://doi.org/10.1055/s-0030-1255442
14. Tiede A, Giangrande P, Teitel J, et al. Clinical evaluation of bleeds and response to haemostatic treatment in patients with acquired haemophilia: a global expert consensus statement. Haemophilia 2019;25:969-78. DOI: https://doi.org/10.1111/hae.13844
15. Mannucci PM, Franchini M. Porcine recombinant factor VIII: an additional weapon to handle anti-factor VIII antibodies. Blood Transfus 2017;15:365-8.
16. Tiede A, Klamroth R, Scharf RE, et al. Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study. Blood 2015;125:1091-7. DOI: https://doi.org/10.1182/blood-2014-07-587089
17. Mingot-Castellano ME, Pardos-Gea J, Haya S, et al.; Acquired Haemophilia Spanish Registry of the Spanish Society of ThrombosisHaemostasis (SETH). Management of acquired hemophilia A: results from the Spanish registry. Blood Adv 2021;5:3821-9. DOI: https://doi.org/10.1182/bloodadvances.2021004626
18. Schep SJ, van Dijk WEM, Beckers EAM, et al. Treatment of acquired hemophilia A, a balancing act: results from a 27-year Dutch cohort study. Am J Hematol 2021;96:51-9. DOI: https://doi.org/10.1002/ajh.26009
19. Mostkowska A, Rousseau G, Raynal NJ. Repurposing of rituximab biosimilars to treat B cell mediated autoimmune diseases. FASEB J 2024;38:e23536. DOI: https://doi.org/10.1096/fj.202302259RR
20. Wiestner A, Cho HJ, Asch AS, e al. Rituximab in the treatment of acquired factor VIII inhibitors. Blood 2002;100:3426-8. DOI: https://doi.org/10.1182/blood-2002-03-0765
21. Franchini M, Mannucci PM. Inhibitor eradication with rituximab in haemophilia: where do we stand? Br J Haematol 2014;165:600-8. DOI: https://doi.org/10.1111/bjh.12829
22. Franchini M. Rituximab in the treatment of adult acquired hemophilia A: a systematic review. Crit Rev Oncol Hematol 2007;63:47-52. DOI: https://doi.org/10.1016/j.critrevonc.2006.11.004
23. Collins P, Baudo F, Knoebl P, et al; EACH2 registry collaborators. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). Blood 2012;120:47–55. DOI: https://doi.org/10.1182/blood-2012-02-409185
24. Yu D, Xue F, Liu X, et al. Acquired hemophilia A: a single-center study of 165 patients. Res Pract Thromb Haemost 2024;8:102318. DOI: https://doi.org/10.1016/j.rpth.2024.102318
25. Simon B, Ceglédi A, Dolgos J, et al. Combined immunosuppression for acquired hemophilia A: CyDRi is a highly effective low-toxicity regimen. Blood 2022;140:1983-92. DOI: https://doi.org/10.1182/blood.2022016873
26. Wang P, Zhou R, Zhou H, et al. Single-dose rituximab plus glucocorticoid versus cyclophosphamide plus glucocorticoid in patients with newly diagnosed acquired hemophilia A: a multicenter, open-label, randomized non inferiority trial. Am J Hematol 2024;99:28-37. DOI: https://doi.org/10.1002/ajh.27128
27. Lévesque H, Viallard JF, Houivet E, et al. Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients. Thromb Res 2024;237:79-87. DOI: https://doi.org/10.1016/j.thromres.2024.03.012
28. Franchini M, Marano G, Pati I, et al. Emicizumab for the treatment of haemophilia A: a narrative review. Blood Transfus 2019;17:223-8.
29. Tiede A, Kemkes-Matthes B, Knöbl P. Should emicizumab be used in patients with acquired hemophilia A? J Thromb Haemost 2021;19:637-44. DOI: https://doi.org/10.1111/jth.15208
30. Pasca S, Zanon E, Mannucci PM, Peyvandi F. Emicizumab in acquired hemophilia A: pros and cons of a new approach to the prevention and treatment of bleeding. Blood Transfus 2023;21(6):549-56.
31. Regling K, Sidonio RF Jr. Factor VIII stimulants and other novel therapies for the treatment of von Willebrand disease: what's new on the horizon? Expert Opin Pharmacother 2024;25:1427-38. DOI: https://doi.org/10.1080/14656566.2024.2391526
32. Thomas VM, Abou-Ismail MY, Lim MY. Off-label use of emicizumab in persons with acquired haemophilia A and von Willebrand disease: A scoping review of the literature. Haemophilia 2022;28:4-17. DOI: https://doi.org/10.1111/hae.14450
33. Knoebl P, Thaler J, Jilma P, et al. Emicizumab for the treatment of acquired hemophilia A. Blood 2021;137:410-9. DOI: https://doi.org/10.1182/blood.2020006315
34. Iarossi M, Hermans C. Emicizumab as first-line therapy in acquired hemophilia A. Res Pract Thromb Haemost 2024;8:102438. DOI: https://doi.org/10.1016/j.rpth.2024.102438
35. Shima M, Amano K, Ogawa Y, et alK. A prospective, multicenter, open-label phase III study of emicizumab prophylaxis in patients with acquired hemophilia A. J Thromb Haemost 2023;21:534-45. DOI: https://doi.org/10.1016/j.jtha.2022.10.004
36. Shima M, Suzuki N, Nishikii H, et al. Final analysis results from the AGEHA study: emicizumab prophylaxis for acquired hemophilia A with or without immunosuppressive therapy. Thromb Haemost 2024. Epub ahead of print. DOI: https://doi.org/10.1055/a-2384-3585
37. Tiede A, Hart C, Knöbl P, et al. Emicizumab prophylaxis in patients with acquired haemophilia A (GTH-AHA-EMI): an open-label, single-arm, multicentre, phase 2 study. Lancet Haematol 2023;10:e913-21. DOI: https://doi.org/10.1016/S2352-3026(23)00280-6
38. Hart C, Klamroth R, Sachs UJ, et al. Emicizumab versus immunosuppressive therapy for the management of acquired hemophilia A. J Thromb Haemost 2024;22:2692-701. DOI: https://doi.org/10.1016/j.jtha.2024.06.010
39. Howard M, McKinley D, Sanabria F, Ko RH, Nissen F. Evaluation of the safety of emicizumab prophylaxis in persons with hemophilia A: An updated summary of thrombotic events and thrombotic microangiopathies [abstract]. Blood 2021;138:3186. DOI: https://doi.org/10.1182/blood-2021-146147
40. Pfrepper C, Klamroth R, Oldenburg J, et al. Emicizumab for the treatment of acquired hemophilia A: consensus recommendations from the GTH-AHA Working Group. Hamostaseologie 2024;44:466-71. DOI: https://doi.org/10.1055/a-2197-9738
41. Siragusa S, Napolitano M. Future directions in acquired hemophilia A. Blood 2021;137:294-5. DOI: https://doi.org/10.1182/blood.2020008379
How to Cite
1.
Franchini M, Focosi D. The changing landscape of treatment for acquired hemophilia A. Bleeding Thromb Vascul Biol [Internet]. 2025 Jan. 30 [cited 2025 Nov. 24];4(1). Available from: https://www.btvb.org/btvb/article/view/157
Copyright (c) 2025 The Author(s)
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