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Semin Thromb Hemost 2024; 50(05): 695-713
DOI: 10.1055/s-0043-1778103
Review Article

Shifting Paradigms and Arising Concerns in Severe Hemophilia A Treatment

Rubhan Chandran
1   Department of Pathology, Haematology Unit, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
2   Faculty of Pharmaceutical Sciences, Department of Pharmaceutical Biology, UCSI University, Jalan Puncak Menara Gading, Taman Connaught, Cheras, Kuala Lumpur, Malaysia
,
Eusni R. Mohd. Tohit
1   Department of Pathology, Haematology Unit, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
,
Johnson Stanslas
3   Department of Medicine, Pharmacotherapeutics Unit, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Norazlinaliza Salim
4   Centre of Foundation Studies for Agricultural Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
5   Integrated Chemical Biophysics Research, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Tuan M.T. Mahmood
6   Faculty of Pharmacy, The National University of Malaysia (UKM), Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia
,
Mogana Rajagopal
2   Faculty of Pharmaceutical Sciences, Department of Pharmaceutical Biology, UCSI University, Jalan Puncak Menara Gading, Taman Connaught, Cheras, Kuala Lumpur, Malaysia
› Author Affiliations Funding This project was funded by the Fundamental Research Grant Scheme (FRGS/1/2015/SKK08/UPM/02/8) from the Ministry of Higher Education, Malaysia.
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Abstract

The management of hemophilia A has undergone a remarkable revolution, in line with technological advancement. In the recent past, the primary concern associated with Factor VIII (FVIII) concentrates was the risk of infections, which is now almost resolved by advanced blood screening and viral inactivation methods. Improving patients' compliance with prophylaxis has become a key focus, as it can lead to improved health outcomes and reduced health care costs in the long term. Recent bioengineering research is directed toward prolonging the recombinant FVIII (rFVIII) coagulant activity and synthesising higher FVIII yields. As an outcome, B-domain deleted, polyethylene glycolated, single-chain, Fc-fused rFVIII, and rFVIIIFc-von Willebrand Factor-XTEN are available for patients. Moreover, emicizumab, a bispecific antibody, is commercially available, whereas fitusiran and tissue factor pathway inhibitor are in clinical trial stages as alternative strategies for patients with inhibitors. With these advancements, noninfectious complications, such as inhibitor development, allergic reactions, and thrombosis, are emerging concerns requiring careful management. In addition, the recent approval of gene therapy is a major milestone toward a permanent cure for hemophilia A. The vast array of treatment options at our disposal today empowers patients and providers alike, to tailor therapeutic regimens to the unique needs of each individual. Despite significant progress in modern treatment options, these highly effective therapies are markedly more expensive than conventional replacement therapy, limiting their access for patients in developing countries.

Keywords

hemophilia A - factor VIII - gene therapy - bioengineering - emicizumab - half-life - safety


Publication History

Article published online:
15 January 2024

© 2024. Thieme. All rights reserved.

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