Dahl-FVIII^−/− rats exhibit impaired blood coagulation functions and are prone to development of anti-FVIII immune responses. Pathophysiological properties in Dahl-FVIII^−/− rats were characterized by native ROTEM analysis and TGA of whole blood. Blood samples were collected from the ventral tail artery by using sodium citrate as an anticoagulant. (A) Whole-blood clotting time determined by using native ROTEM analysis. Recalcified whole-blood samples were used for ROTEM analysis. (B) Lag time determined by using nWB-TGA. Recalcified whole blood samples were used for nWB-TGA. (C) Incidence of anti-FVIII inhibitor development in FVIII^−/− rats that had spontaneous bleeding episodes and received human recombinant FVIII infusion. (D) Inhibitor titers in FVIII^−/− rats that had spontaneous bleeding episodes and received human recombinant FVIII infusion. Blood samples were collected from animals at least 2 weeks after rhFVIII infusion, and anti-FVIII inhibitor titers were determined by using a chromogenic-based modified Bethesda assay.