Relationship between iron deposits and tissue damage in the synovium: an ultrastructural study.

Morris, C J; Blake, David R.; Wainwright, A C; Steven, M. M.

doi:10.1136/ard.45.1.21

Cited by 99 publications

(68 citation statements)

References 29 publications

(5 reference statements)

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“…53 Free iron promotes inflammation and cellular proliferation 54,55 and is thought to play a role in the synovitis and excess angiogenesis observed in patients with hemophilia following repeated hemorrhage into a target joint. 56,57 Thus, the defect in macrophage influx, accumulation of tissue iron, and the excess angiogenesis in HB mice may all be linked.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous wound healing is impaired in hemophilia B

Hoffman

Harger

Lenkowski

et al. 2006

Blood

102

145

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We used a mouse model to test the hypothesis that the time course and histology of wound healing is altered in hemophilia B. Punch biopsies (3 mm) were placed in the skin of normal mice and mice with hemophilia. The size of the wounds was measured daily until the epidermal defect closed. All wounds closed in mice with hemophilia by 12 days, compared with 10 days in normal animals. Skin from the area of the wound was harvested at different time points and examined histologically. Hemophilic animals developed subcutaneous hematomas; normal animals did not. Macrophage infiltration was significantly delayed in hemophilia B. Unexpectedly, hemophilic mice developed twice as many blood vessels in the healing wounds as controls, and the increased vascularity persisted for at least 2 weeks. The deposition and persistence of ferric iron was also greater in hemophilic mice. We hypothesize that iron plays a role in promoting excess angiogenesis after wounding as it had been proposed to do in hemophilic arthropathy. We have demonstrated that impaired coagulation leads to delayed wound healing with abnormal histology. Our findings have significant implications for treatment of patients with hemophilia, and also highlight the importance of rapidly establishing hemostasis following trauma or surgery. (Blood. 2006; 108:3053-3060)

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Section: Discussionmentioning

confidence: 99%

Cutaneous wound healing is impaired in hemophilia B

Hoffman

Harger

Lenkowski

et al. 2006

Blood

102

145

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show abstract

“…Some authors [6][7][8][9] suggest that intra-articular blood has a precursor direct effect on cartilage, as a result of the iron-catalysed formation of destructive oxygen metabolites, subsequently affecting the synovium. Other authors [10,11] suggest that there is a hemosiderin-induced synovial triggering process. Nevertheless, most likely both processes occur in parallel, and while they influence each other, they probably do not depend on each other.…”

Section: Introductionmentioning

confidence: 99%

State‐of‐the‐art imaging techniques for the evaluation of haemophilic arthropathy: present and future

Doria

2010

Haemophilia

102

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Summary. In spite of the fact that the diagnosis of haemophilia is essentially clinical and laboratorybased, imaging has become an important tool for the evaluation of complications, diagnostic confirmation and/or complementation and therapeutic follow-up in haemophilic arthropathy. Radiography remains the workforce horse in the diagnosis and follow-up of haemophilic arthropathy. The radiographical findings in arthropathy follow an expected sequence of events and are overall similar in different joints. Magnetic resonance imaging (MRI) has advantages over radiography based on its capability of visualizing soft tissue and cartilage changes in haemophilic joints. The recent development and standardization of MRI scoring systems for measuring soft tissue and cartilage abnormalities may enable the comparison of pathological joint findings in clinical trials conducted at different institutions across the world. The implementation of high-frequency transducers and colour/power Doppler capabilities has provided new insights for clinical applications of ultrasonography (US) in haemophilic arthropathy. In spite of the imaging modality's technical challenges such as operator-dependency, US has advantages over MRI. One of these advantages is its ability of differentiating synovium hypertrophy and hemosiderin deposition, which is not possible with MRI given the presence of susceptibility artefacts from extracellular hemosiderin on gradient-echo MR images. In addition to the aforementioned conventional imaging modalities, novel imaging techniques (blood oxygen level dependent, ultrasmall superparamagnetic ironoxide contrast-enhanced, and T1 and T2 mapping MRI, ultrasound biomicroscopy, microbubble contrast-enhanced US and positron emission tomography, among others) hold promise for early assessment of haemophilic arthropathy in the future upon completion of their clinical validation.

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“…Morris proposed a central role for iron in HS. 15 Roosendaal et al 14 studied the relationship of iron to the catabolic properties in synovial tissue from patients with hemophilia. Iron deposits were present in the cytoplasm of the lining synovial cells as discrete granules but in subsynovial layers there were dense aggregates located intracellularly and extracellularly.…”

Section: Discussionmentioning

confidence: 99%

“…Iron is often proposed as one possibility. [13][14][15] Iron plays a role in malignant cell growth, 16,17 local invasion, and tumor progression, possibly due to changes in the expression of oncogenes. 13 We hypothesized that iron plays a similar role in HS.…”

Section: Introductionmentioning

confidence: 99%