Fitusiran treatment modulates the ratio between alpha‐ and beta‐antithrombin isoforms
-mice and fitusiran-treated patients, respectively (P < 0.0001). Furthermore, the ratio of beta-AT/total AT antigen levels increased 1.8-fold in the human patient samples (from 0.09 ± 0.03 to 0.16 ± 0.01; P = 0.003), which coincided with an increased intensity of the beta-AT band detected in immunoprecipitation assays. It is noteworthy that this increase in the beta-AT/total AT ratio significantly increased its anticoagulant potential. Finally, we measured beta-AT/total AT ratios also in unrelated pathologies: congenital AT deficiency and advanced liver cirrhosis. Both conditions were also associated with an up to twofold higher ratio of beta-AT/total AT. Altogether, our results demonstrate that reduced AT production modulates the ratio between beta-AT and alpha-AT.
Authors
- Geneviève McCluskey
- Elsa P. Bianchini (ORCID: https://orcid.org/0000-0002-1370-5312)
- Cécile V. Denis (ORCID: https://orcid.org/0000-0001-5152-9156)
- Peter J. Lenting (ORCID: https://orcid.org/0000-0002-7937-3429)
- Caterina Casari (ORCID: https://orcid.org/0000-0002-8271-6795)
- Delphine Borgel (ORCID: https://orcid.org/0000-0002-8847-8935)
- Olivier D. Christophe (ORCID: https://orcid.org/0000-0002-9080-6336)
- Laurent Frenzel (ORCID: https://orcid.org/0000-0002-6085-2163)
- Hortense Maynadié
Institutions
- Hôpital Necker-Enfants Malades (FR)
- Inserm (FR)
- Université Paris-Saclay (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Centre Hospitalier Régional et Universitaire de Nancy (FR)
- Hemostase Inflammation Thrombosis (FR)
- Bicêtre Hospital (FR)
- Hôpital Paul-Brousse (FR)
Publication Details
- Journal
- HemaSphere
- Published
- 2026-05-01
- DOI
- https://doi.org/10.1002/hem3.70376
- Primary Topic
- Atrial Fibrillation Management and Outcomes
- Type
- article
- Field-Weighted Citation Impact
- 0.00