Hemophilia is due to the deficiency of the activity of coagulation factor VIII or IX and results in bleeding. Hemarthrosis frequently leads to synovitis and arthropathy in adolescents and adults with severe disease. The molecular basis for this disorder is only recently being interrogated in detail (Wen, Jabbar et al. 2002; Hakobyan, Kazarian et al. 2004; Valentino, Hakobyan et al. 2004; Hakobyan, Kazarian et al. 2005). In addition to proliferation of synovial fibroblasts, vessels are prominent and likely play a fundamental role. We hypothesized that synovial hyperplasia was limited by the degree of tissue vascularization and a direct relationship between the expansions of these two tissues existed. To test this hypothesis, mouse knee joints were injured by blunt or surgical trauma to induce hemarthrosis or blood was directly injected into the joint capsule to induce synovitis then the knees isolated and the tissues examined by seven reviewers blinded to the experimental conditions for the extent of synovial and vessel hyperplasia (Valentino and Hakobyan 2006, in press) and their individual scores averaged. The distribution of the scores for the 271 sections is given in the table. A direct relationship (r2=0.90, p<0.001) between synovial and vessel hyperplasia was present (figure). It is likely that the synovial membrane can expand up to a point (grade 1) but beyond this, vessel hyperplasia is necessary and that progressive hypertrophy of the synovial membrane is dependent upon the development of vessels to provide oxygen and nutrients. The production of vascular trophic factors by synovial fibroblast cells is under investigation.

Types and numbers of hyperplasia

Hyperplasia 
Synovial 149 67 18 37 
Vascular 180 58 19 14 
Hyperplasia 
Synovial 149 67 18 37 
Vascular 180 58 19 14 

Disclosure: No relevant conflicts of interest to declare.

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