On-demand Treatment with the Iron Chelator Deferasirox is Ineffective in Preventing Blood-induced Joint Damage in Haemophilic Mice

Overview

Journal Haemophilia

Specialty Hematology

Date 2021 May 27

PMID 34043875

Citations 2

Authors

Astrid E Pulles

Lize F D van Vulpen

Katja Coeleveld

Simon C Mastbergen

Roger E G Schutgens

Floris P J G Lafeber

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Maladaptive lymphangiogenesis is associated with synovial iron accumulation and delayed clearance in factor VIII-deficient mice after induced hemarthrosis.

Cooke E, Joseph B, Nasamran C, Fisch K, von Drygalski A J Thromb Haemost. 2023; 21(9):2390-2404.

PMID: 37116753 PMC: 10792547. DOI: 10.1016/j.jtha.2023.04.022.

Pain in Hemophilia: Unexplored Role of Oxidative Stress.

Fouda R, Argueta D, Gupta K Antioxidants (Basel). 2022; 11(6).

PMID: 35740010 PMC: 9220316. DOI: 10.3390/antiox11061113.

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