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Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against factor VIII, with a high mortality risk. It should be suspected in subjects with abnormal bleedings, especially subcutaneous bleed associated with prolonged activated partial thromboplastin time (aPTT). AHA is often idiopathic but is associated with autoimmune diseases, malignancies, pregnancy and postpartum period or drugs. Treatment is based on haemostatic agents as by-passants agents such as factor VIIa and activated prothrombine concentrate complex or recombinant porcine factor VIII for severe bleeding. Eradication of inhibitor should be established as soon as the diagnosis is confirmed with steroid alone often associated with cytotoxic agents or rituximab, depending on FVIII activity and inhibitor titer. The purpose of this review is to summarize the epidemiology, etiopathogenesis, diagnosis, treatment of AHA and discuss current recommendations., (Copyright © 2024. Published by Elsevier Masson SAS.)

Résumé: Le facteur VIII (FVIII) est une protéine de la cascade de coagulation qui exerce une activité de cofacteur non enzymatique vis-à-vis du facteur IXa (FIXa), l'enzyme qui va promouvoir l'activation du facteur X (FX). Un déficit fonctionnel en FVIII conduit à l'hémophilie A, une pathologie hémorragique grave dont la prévalence se situe autour de 1-2 cas pour 10 000 naissances de garçons. La prise en charge des complications hémorragiques associées à l'hémophilie A s'effectue par une thérapie de substitution visant à remplacer le FVIII manquant, préférentiellement par prophylaxie. En raison des limites inhérentes à cette approche (avec la nécessité d'infusions intraveineuses fréquentes et l'apparition d'anticorps inhibiteurs contre le FVIII thérapeutique), de nouvelles thérapies ont récemment été développées. L'emicizumab, un anticorps bispécifique, en est un représentant. Cet anticorps a pour fonction de mimer l'activité cofacteur du FVIII en permettant un rapprochement dans l'espace du FIXa et du FX. Dans cette revue, nous discuterons des aspects fonctionnels et cliniques de l'emicizumab, nous comparerons son mode d'action à celui du FVIII et les implications pour le suivi biologique des patients. De plus, nous présenterons les données cliniques obtenues dans les essais pivots HAVEN qui ont montré un bénéfice significatif de l'emicizumab avec une réduction importante des saignements spontanés chez les patients traités. Finalement, nous discuterons des effets secondaires associés à l'utilisation de l'emicizumab et nous conclurons sur son utilisation potentielle au-delà de l'hémophilie A. Coagulation factor VIII (FVIII) functions as a non-enzymatic cofactor for the enzyme factor IXa (FIXa) in the activation of factor X (FX). The functional deficiency of FVIII is associated with a severe bleeding disorder known as hemophilia A, affecting 1-2 per 10,000 male births. Bleeding complications have long been managed via FVIII substitution therapy, preferably on a prophylactic basis. Due to limitations of this approach (i.e., the need for frequent intravenous infusions, development of neutralizing antibodies), novel treatment options for hemophilia A have been evaluated, including the use of the bispecific antibody emicizumab. Emicizumab is designed to mirror FVIII cofactor function by promoting the spatial approximation of FIXa and FX. In this review, we will discuss functional and clinical aspects of emicizumab. We will compare its mode of action to that of FVIII and consider the implications for laboratory monitoring of this antibody. In addition, we highlight the clinical data obtained in the pivotal HAVEN-trials, which have shown a clear clinical benefit by strongly reducing the occurrence of spontaneous bleeding episodes. Finally, we discuss some of the adverse effects that have been reported and also the potential use of emicizumab beyond patients with severe hemophilia A. [ABSTRACT FROM AUTHOR]

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Since March 2019, émicizumab is indicated for the treatment of patients with severe haemophilia A without inhibitor. This therapy's price amounts approximately to €33 600 per 4 weeks for a 70kg patient which represents about two times more than a factor VIII concentrates treatment's price. This study aims to assess the budgetary impact for the French Health Insurance of an émicizumab therapy introduction for patients with severe haemophilia A without inhibitor. It was an observational, retrospective, and monocentric study. Every severe haemophilia A without inhibitor patient over 18 years old followed at the Cochin Hospital haemophilia treatment centre who received émicizumab from June 2020 and for at least one year have been included. The budgetary impact was estimated by comparing the total costs of patient care the year before versus the year after émicizumab initiation. Total costs of patient care included prices of i) treatments consumed, ii) consultations with specialist physicians, iii) hospitalizations and iv) imaging procedures. Thirty-eight patients were included. The total cost of patient care increased significantly the year after émicizumab introduction (P < 0.0001). On average, this cost was estimated at €537 887 ± €137 139 per patient whereas it was at €151 442 ± €94 708 the year before. While costs of physician consultations increased, no significant difference has been reported about hospitalizations and imaging costs. Over a one-year period, émicizumab therapy significantly increased the total costs of patient care. It is mostly caused by the drug price itself., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Since 2019, severe haemophilia A without inhibitors can be treated with emicizumab. Its action, route of administration and management justified the creation of new tools for therapeutic education sessions addressed to patients. The main objective of our work was to assess the knowledge and skills acquired by patients after therapeutic education. The various documents created were a video, a slideshow, clinical cases in form of cards, and summary sheets intended for patients. At treatment beginning, a pharmaceutical consultation was proposed to all patients. Two months later, an evaluation was carried out and a second pharmaceutical consultation aimed to consolidate the achievements of patients. Simultaneously, a clinical self-evaluation by the patients was carried out. Thirty-six patients were included in the study. Theoretical items: method of manufacture, mechanism of action and regimen, are known for more than ¾ of patients. Practical skills, such as administration modalities, management of missed doses or bleeding, are familiar for more than 8 out of 10 patients. Sixteen (44.4%) patients presented an up-to-date haemophilia card. The assessment of the knowledge and skills of patients is encouraging since most of the items are acquired. These result highlights the interest of the new tools developed for the therapeutic education sessions., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Recent therapeutic innovations are significantly changing the management of young children with severe haemophilia. A team from the University Hospital of Nice (06) introduced emicizumab, the first subcutaneous non-replacement therapy. Integrated into the multi-professional management of children and their families, this innovative therapeutic option has shown encouraging initial results. Experience sharing., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)