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On‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice
INTRODUCTION: Early intervention in the devastating process of haemophilic arthropathy (HA) is highly desirable, but no disease‐modifying therapy is currently available. Considering the pivotal role of iron in the development of HA, iron chelation is considered a promising therapeutic approach. A pr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361985/ https://www.ncbi.nlm.nih.gov/pubmed/34043875 http://dx.doi.org/10.1111/hae.14328 |
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author | Pulles, Astrid E. van Vulpen, Lize F. D. Coeleveld, Katja Mastbergen, Simon C. Schutgens, Roger E. G. Lafeber, Floris P. J. G. |
author_facet | Pulles, Astrid E. van Vulpen, Lize F. D. Coeleveld, Katja Mastbergen, Simon C. Schutgens, Roger E. G. Lafeber, Floris P. J. G. |
author_sort | Pulles, Astrid E. |
collection | PubMed |
description | INTRODUCTION: Early intervention in the devastating process of haemophilic arthropathy (HA) is highly desirable, but no disease‐modifying therapy is currently available. Considering the pivotal role of iron in the development of HA, iron chelation is considered a promising therapeutic approach. A previous study in haemophilic mice demonstrated that treatment with the iron chelator deferasirox (DFX) 8 weeks before joint bleed induction, attenuated cartilage damage upon blood exposure. However, in haemophilia patients this approach is not opportune given the unpredictable occurrence of hemarthroses. AIM: To evaluate the effectiveness of on‐demand DFX treatment, initiated immediately after joint bleed induction. METHODS: A joint bleed was induced in 66 factor VIII‐deficient mice by infra‐patellar needle puncture. Mice were randomly assigned to treatment with either placebo (drinking water) or DFX (dissolved in drinking water) throughout the study. Five weeks after joint bleed induction, inflammation and cartilage damage were assessed histologically. Joints of ten bleed naive haemophilic mice served as controls. RESULTS: A joint bleed resulted in significant inflammation and cartilage damage in the blood‐exposed joint compared with those of control animals, in both the placebo and DFX group (all p = <.05). No differences in tibiofemoral or patellar inflammation (p = .305 and p = .787, respectively) nor cartilage damage (p = .265 and p = .802, respectively) were found between the blood‐exposed joints of both treatment groups. CONCLUSION: On‐demand treatment with DFX does not prevent joint damage following blood exposure in haemophilic mice. DFX seems unable to reach the joint in time to exert its effect before the irreversible harmful process is initiated. |
format | Online Article Text |
id | pubmed-8361985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83619852021-08-17 On‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice Pulles, Astrid E. van Vulpen, Lize F. D. Coeleveld, Katja Mastbergen, Simon C. Schutgens, Roger E. G. Lafeber, Floris P. J. G. Haemophilia Original Articles INTRODUCTION: Early intervention in the devastating process of haemophilic arthropathy (HA) is highly desirable, but no disease‐modifying therapy is currently available. Considering the pivotal role of iron in the development of HA, iron chelation is considered a promising therapeutic approach. A previous study in haemophilic mice demonstrated that treatment with the iron chelator deferasirox (DFX) 8 weeks before joint bleed induction, attenuated cartilage damage upon blood exposure. However, in haemophilia patients this approach is not opportune given the unpredictable occurrence of hemarthroses. AIM: To evaluate the effectiveness of on‐demand DFX treatment, initiated immediately after joint bleed induction. METHODS: A joint bleed was induced in 66 factor VIII‐deficient mice by infra‐patellar needle puncture. Mice were randomly assigned to treatment with either placebo (drinking water) or DFX (dissolved in drinking water) throughout the study. Five weeks after joint bleed induction, inflammation and cartilage damage were assessed histologically. Joints of ten bleed naive haemophilic mice served as controls. RESULTS: A joint bleed resulted in significant inflammation and cartilage damage in the blood‐exposed joint compared with those of control animals, in both the placebo and DFX group (all p = <.05). No differences in tibiofemoral or patellar inflammation (p = .305 and p = .787, respectively) nor cartilage damage (p = .265 and p = .802, respectively) were found between the blood‐exposed joints of both treatment groups. CONCLUSION: On‐demand treatment with DFX does not prevent joint damage following blood exposure in haemophilic mice. DFX seems unable to reach the joint in time to exert its effect before the irreversible harmful process is initiated. John Wiley and Sons Inc. 2021-05-27 2021-07 /pmc/articles/PMC8361985/ /pubmed/34043875 http://dx.doi.org/10.1111/hae.14328 Text en © 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Pulles, Astrid E. van Vulpen, Lize F. D. Coeleveld, Katja Mastbergen, Simon C. Schutgens, Roger E. G. Lafeber, Floris P. J. G. On‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice |
title | On‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice |
title_full | On‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice |
title_fullStr | On‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice |
title_full_unstemmed | On‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice |
title_short | On‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice |
title_sort | on‐demand treatment with the iron chelator deferasirox is ineffective in preventing blood‐induced joint damage in haemophilic mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361985/ https://www.ncbi.nlm.nih.gov/pubmed/34043875 http://dx.doi.org/10.1111/hae.14328 |
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