• L Nieuwenhuizen, G Roosendaal, S C Mastbergen, K Coeleveld, D H Biesma, F P J G Lafeber, and R E G Schutgens.
• Rheumatology & Clinical Immunology, University Medical Center, Utrecht, The Netherlands; Hematology & Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands.
• J. Thromb. Haemost. 2014 Feb 1; 12 (2): 237-45.

BackgroundBlood-induced joint damage is characterized by synovitis and cartilage damage. Recently, we demonstrated that joint bleeding in hemophilic mice results in elevated synovial levels of urokinase plasminogen activator (u-PA) and plasmin, and in plasmin-mediated cartilage damage.ObjectiveTo evaluate whether treatment with amiloride (an inhibitor of u-PA) or antiplasmin attenuates synovitis and cartilage damage following joint bleeding in hemophilic mice.MethodsFollowing the induction of joint bleeding, hemophilic mice were randomized between daily oral treatment with amiloride (1 mg kg⁻¹) or control, or weekly intra-articular treatment with amiloride (2.5 mg mL⁻¹), antiplasmin (2.5 mg mL⁻¹), or control. After 5 weeks of treatment, synovitis and cartilage damage were determined on hematoxylin and eosin-stained (Valentino score) and Safranin O-stained sections, respectively.ResultsNo effects of oral and intra-articular treatment with amiloride were found. In contrast, intra-articular treatment with antiplasmin resulted in significant (P < 0.01) reductions in both synovitis (score 1, 11.1% vs. 0%; score 2, 11.1% vs. 4.2%; score 3, 61.1% vs. 16.7%; score 4, 5.6% vs. 29.2%; score 5, 11.1% vs. 20.8%; score 6, 7.7% vs. 8.3%; score 7, 0% vs. 8.3%; and score 8, 0% vs. 12.5%) and cartilage damage (score 2, 10% vs. 8.3%; score 3, 50% vs. 12.5%; score 4, 30% vs. 33.3%; score 5, 10% vs. 33.3%; and score 6, 0% vs. 16.7%) as compared with controls.ConclusionsIntra-articular treatment with antiplasmin (but not amiloride) following joint bleeding prevented synovitis and cartilage damage in hemophilic mice. These data offer promise for the use of antiplasmin as a new therapeutic intervention for patients who suffer from joint bleeds despite administration of clotting factor.© 2013 International Society on Thrombosis and Haemostasis.

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