Histone-induced platelet activation is partially dependent on TLR2 and TLR4. Flow cytometric analysis of PS exposure (A), P-selectin expression (B), and FV/Va expression (C) in gel-filtered platelets stimulated with histones (40 μg/mL) with or without preincubation with mouse monoclonal anti–human TLR2 or TLR4 blocking Abs (50 μg/mL) or control mouse IgG2a for 20 minutes at RT. Data are means ± SD, n = 3. *P < .05. (D) Thrombin generation induced by histones (40 μg/mL) in CTI-inhibited PRP pretreated with neutralizing mAbs against TLR2, TLR4, or control Ab. Representative thrombograms of 3 experiments are shown.