Antithrombin lowering in hemophilia: a closer look at fitusiran.
antithrombin
fitusiran
hemophilia
small interfering RNA
thrombin
Journal
Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
03
11
2022
revised:
20
04
2023
accepted:
08
05
2023
medline:
26
6
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
epublish
Résumé
Thrombin is a key enzyme in the maintenance of normal hemostatic function and is the central product of an interconnected set of simultaneously occurring cellular and proteolytic events. Antithrombin (AT) is a natural anticoagulant that downregulates different components of the clotting process, particularly thrombin generation. In good health, well-regulated hemostasis is the result of a balance between procoagulant and anticoagulant elements. Cumulative understanding of the regulation of thrombin generation and its central role in hemostasis and bleeding disorders has led to the clinical development of therapeutic strategies that aim to rebalance hemostasis in individuals with hemophilia and other coagulation factor deficiencies to improve bleeding phenotype. The aim of this review is to discuss the rationale for AT lowering in individuals with hemophilia, with a focus on fitusiran, its mechanism of action, and its potential as a prophylactic therapy for individuals with hemophilia A or B, with or without inhibitors. Fitusiran is an investigational small, interfering RNA therapeutic that targets and lowers AT. It is currently in phase III clinical trials and results have shown its potential to increase thrombin generation, leading to enhanced hemostasis and improved quality of life while reducing the overall treatment burden.
Identifiants
pubmed: 37358958
doi: 10.1016/j.rpth.2023.100179
pii: S2475-0379(23)00152-8
pmc: PMC10285540
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
100179Informations de copyright
© 2023 The Authors.
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