Figure 5
Figure 5. Effect of monocyte depletion on platelet count and thrombosis in the HIT model. (A) Platelet counts after induction of HIT in the FcγRIIA+/hPF4+ mice model. Clodronate- or PBS-laden liposomes were injected intravenously. Twelve hours later (Time 0), KKO 2.5 mg/kg was administered intraperitoneally. The first platelet count was measured 4 hours later. Animals receiving no liposomes (○) or PBS-laden liposomes (▩) had modest thrombocytopenia compared with the same mice receiving clodronate-laden liposomes (♦). N ≥ 3, each in duplicate. Mean ± 1 SE are shown. *P < .05 for platelet drop after KKO in mice with depleted monocytes versus control mice. (B) Same as panel A but animals received NaCl (open symbols) or GdCl3 (black symbols) 32 hours prior to the KKO 10 mg/kg intraperitoneal injection (diamonds) or controls without KKO (circles). N ≥ 3, each in duplicate. Mean ± 1 SE are shown. *P < .05 for platelet drop in mice treated with GdCl3 followed by KKO versus mice treated with NaCl followed by KKO. (C) Times to complete occlusion in a photochemical carotid artery model in FcγRIIA+/hPF4+ mice under conditions noted in the figure are shown as mean ± 1 SE. The platelet counts at the time of study are indicated above each bar and is per 109/mL. N values are noted in the figures. *P < .001 for time to occlusion relative to mice not receiving either KKO or liposomes.

Effect of monocyte depletion on platelet count and thrombosis in the HIT model. (A) Platelet counts after induction of HIT in the FcγRIIA+/hPF4+ mice model. Clodronate- or PBS-laden liposomes were injected intravenously. Twelve hours later (Time 0), KKO 2.5 mg/kg was administered intraperitoneally. The first platelet count was measured 4 hours later. Animals receiving no liposomes (○) or PBS-laden liposomes (▩) had modest thrombocytopenia compared with the same mice receiving clodronate-laden liposomes (♦). N ≥ 3, each in duplicate. Mean ± 1 SE are shown. *P < .05 for platelet drop after KKO in mice with depleted monocytes versus control mice. (B) Same as panel A but animals received NaCl (open symbols) or GdCl3 (black symbols) 32 hours prior to the KKO 10 mg/kg intraperitoneal injection (diamonds) or controls without KKO (circles). N ≥ 3, each in duplicate. Mean ± 1 SE are shown. *P < .05 for platelet drop in mice treated with GdCl3 followed by KKO versus mice treated with NaCl followed by KKO. (C) Times to complete occlusion in a photochemical carotid artery model in FcγRIIA+/hPF4+ mice under conditions noted in the figure are shown as mean ± 1 SE. The platelet counts at the time of study are indicated above each bar and is per 109/mL. N values are noted in the figures. *P < .001 for time to occlusion relative to mice not receiving either KKO or liposomes.

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