NAC is not effective in reversing TTP signs in Adamts13^−/− mice despite a reduction in HMW VWF multimers. (A) Adamts13^−/− mice (n = 10 per group) were injected with rVWF to trigger TTP signs. One hour and 12 hours later, mice were injected with 800 mg/kg NAC (open blue circles) or equal volumes of saline for control (solid red circles). (B-C) At baseline and 24 hours after rVWF injection, platelet count (B), hemoglobin level (C), and LDH activity level (D) were determined. (E) H&E staining was performed on myocardial tissue sections from control mice (upper panel) and mice with prophylactic NAC administration (lower panel). Arrows indicate sites of myocardial necrosis. Scale bars indicate 50 μm. (F) VWF multimer composition was analyzed and representative images of VWF multimeric profiles from a control mouse and NAC mouse are shown. (G) Percentage of HMW VWF multimers was quantified using densitometry. Statistical significance is indicated with asterisks: *P < .05, **P < .01, ***P < .001; ns, not significant.