TAFI deficiency eliminates protection against joint bleeding in aHA mice. (A) Joint bleeding after knee injury in FVIII^−/− BALB/c, WT C57Bl/6J, or TAFI^−/− C57Bl/6J mice with or without anti-FVIII antibody (0.25 mg/kg) alone or in combination with anti-TAFI antibody MA-RT36A3F5 (7.5 mg/kg; n = 10-16). Bleeding was determined by measuring Hct at day 2 (D2) postinjury. (B) Photographs of the hematoma formed in the right injured knee at day 4 after injury in a FVIII^−/− BALB/c mouse or an anti-FVIII antibody–treated WT-C57Bl/6J or TAFI^−/− C57Bl/6J mouse. (C) Representative images of Safranin-O fast green staining of the left uninjured knee joint and corresponding right injured knee joint harvested at day 7 postinjury of a WT C57Bl/6J or TAFI^−/− C57Bl/6J mouse injected with anti-FVIII antibody (0.25 mg/kg) or of a FVIII^−/− BALB/c mouse. The yellow line indicates soft tissue expansion between the anterior meniscus and joint capsule. Original magnification, ×4; scale bar = 200 µm. (D) Soft tissue expansion (µm) at baseline (BL) and days 4 and 7 postinjury in WT C57Bl/6J, TAFI^−/− C57Bl/6J, and FVIII^−/− BALB/c mice with and without anti-FVIII antibody (0.25 mg/kg) and/or anti-TAFI antibody (MA-RT36A3F5; 7.5 mg/kg; n = 4-6). Soft tissue expansion was measured as the distance between the anterior meniscus and joint capsule (indicated by the yellow line in Figure 3C). BL indicates baseline without knee injury. Kruskal-Wallis test followed by Dunn’s post hoc multiple comparison test was used to compare experimental mice with their respective baseline controls. *P < .05, **P < .01, ***P < .001, ****P < .0001. ns, not significant.