Summary
Joint bleeds in haemophilia result in iron-mediated synovitis and cartilage damage.
It was evaluated whether deferasirox, an iron chelator, was able to limit the development
of haemophilic synovitis and cartilage damage. Haemophilic mice were randomly assigned
to oral treatment with deferasirox (30 mg/kg) or its vehicle (control) (30 mg/kg).
Eight weeks after start of treatment, haemarthrosis was induced. After another five
weeks of treatment, blood-induced synovitis and cartilage damage were determined.
Treatment with deferasirox resulted in a statistically significant (p< 0.01) decrease
in plasma ferritin levels as compared to the control group (823 ng/ml ± 56 and 1220
ng/ml ±114, respectively). Signs of haemophilic synovitis, as assessed by the Valentino
score [range 0 (normal) – 10 (most affected)], were not different (p=0.52) when comparing
the control group with the deferasirox group. However, deferasirox treatment resulted
in a statistically significant (p< 0.01) reduction in cartilage damage, as assessed
by the loss in Safranin O staining [range 0 (normal) – 6 (most affected)], when comparing
the deferasirox group with the control group: score 2 (65.4 % vs 4.2 %), score 3 (26.9
% vs 4.2 %), score 4 (7.7 % vs 20.8 %), score 5 (0 % vs 54.2 %), and score 6 (0 %
vs 16.7 %). Treatment with deferasirox limits cartilage damage following the induction
of a haemarthrosis in haemophilic mice. This study demonstrates the role of iron in
blood-induced cartilage damage. Moreover, these data indicate that iron chelation
may be a potential prevention option to limit the development of haemophilic arthropathy.
Keywords
Haemophilia - haemarthrosis - blood-induced arthropathy - deferasirox
