Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Haemophilia. 2021 Jul;27(4):648-656. doi: 10.1111/hae.14328. Epub 2021 May 27.
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.
To evaluate the effectiveness of on-demand DFX treatment, initiated immediately after joint bleed induction.
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.
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.
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.
早期干预血友病性关节病（HA）的破坏性过程是非常理想的，但目前尚无针对该病的治疗方法。鉴于铁在 HA 发展中的关键作用，铁螯合作用被认为是一种有前途的治疗方法。先前在血友病小鼠中的研究表明，在关节出血前 8 周用铁螯合剂地拉罗司（DFX）治疗，可以减轻血液暴露后的软骨损伤。然而，由于关节积血的不可预测性，在血友病患者中，这种方法并不合适。
评估按需 DFX 治疗（在关节出血后立即开始）的有效性。
通过髌下针穿刺在 66 只因子 VIII 缺乏的小鼠中诱导关节出血。小鼠被随机分为治疗组和对照组，治疗组给予 DFX（溶于饮用水中）或安慰剂（饮用水）治疗。关节出血 5 周后，进行组织学评估炎症和软骨损伤。10 只未出血的血友病小鼠的关节作为对照。
与对照组相比，关节出血导致暴露于血液的关节出现明显的炎症和软骨损伤，无论是在安慰剂组还是 DFX 组（均 p<.05）。两组中，胫股关节或髌骨关节的炎症（p=.305 和 p=.787）或软骨损伤（p=.265 和 p=.802）均无差异。
在血友病小鼠中，按需给予 DFX 治疗不能预防血液暴露后的关节损伤。DFX 似乎无法及时到达关节，在不可逆的有害过程启动之前发挥作用。
