EPCR blocking reduces the severity of hemophilic synovitis following hemarthrosis in FVIII^−/− mice. FVIII^−/− mice were administered with EPCR-blocking mAb (bl. EPCR mAb), EPCR-nonblocking mAb (non-bl. EPCR mAb), or no mAb (No tr.). Twenty-four hours later, joint bleeding was induced with a needle puncture (I). UN indicates an uninjured knee. Two weeks after the injury, mice were killed, knee joints were excised, and joint tissue sections were processed for histopathological analysis by staining with H&E (A), macrophage marker F4/80 (C), and CD31 antibody to identify blood vessels (E). The red staining (C,E) indicates macrophages and blood vessels, respectively. (A) Two thin black arrows pointing each other indicate width of synovial lining layer, the yellow arrowhead points out red blood cells, and thick black arrows point out synovial villi. Arrows point out macrophages (C) and blood vessels (E). (B) Synovitis score. (D) Macrophage scoring. (F) Number of blood vessels counted per field. Shown are representative images, and data in bar graphs are mean ± SEM (n = 5 to 10 mice/group). ****P < .0001.