CS585 prevents thrombosis in small and large vessels. (A) WT mice were administered vehicle or CS585 (0.5-6 mg/kg), followed by the induction of cremaster arteriole laser-induced injury to assess platelet and fibrin accumulation at the site of injury (n = 3 mice per condition/8 injuries per mouse). Data represent mean ± SEM. Two-way ANOVA. (B) Representative images of panel A showing platelet plug formation (green) and fibrin accumulation (red). Scale bars represent 50 μm. (C) WT mice were administered vehicle or CS585 (0.5-6 mg/kg) and the carotid artery FeCl₃-induced thrombosis model was assessed (n = 5). Data represent mean ± SEM. One-way ANOVA with Dunnett correction. (D) Representative images of panel C. Scale bars represent 500 μm. (E) WT mice were administered vehicle or CS585 (6 mg/kg) and the stability of CS585 in the blood was determined by induction of the cremaster arteriole laser-induced injury to assess platelet and fibrin accumulation at the site of injury at 4 hours and 18 hours after administration (n = 3 mice per condition/8 injuries per mouse). Data represent mean ± SEM. Two-way ANOVA. (F) Representative images of panel E, showing platelet plug formation (green) and fibrin accumulation (red). Scale bars represent 50 μm. (G) WT mice were administered a single dose of vehicle or CS585 (1.5-6 mg/kg) per oral (PO) and the functional efficacy of CS585 in the blood was determined by cremaster arteriole laser-induced injury to assess platelet and fibrin accumulation at the site of injury 4 hours after administration (n = 3 mice per condition/8 injuries per mouse). Data represent mean ± SEM. Two-way ANOVA. (H) Representative images of panel G, showing platelet plug formation (green) and fibrin accumulation (red). Scale bars represent 50 μm. (I) WT mice were administered vehicle or CS585 (3 mg/kg) PO and the stability of CS585 in the blood was determined by cremaster arteriole laser-induced injury to assess platelet and fibrin accumulation at the site of injury 24, 48, and 72 hours after administration (n = 3 mice per condition/8 injuries per mouse). Data represent mean ± SEM. Two-way ANOVA. (J) Representative images of panel I, showing platelet plug formation (green) and fibrin accumulation (red). Scale bars represent 50 μm. (K) Quantification of phosphatidylserine exposure in washed platelets from WT mice IV administered with vehicle or CS585 (6 mg/kg; CS585 [IV]) and stained with annexin V, stimulated with convulxin (50 ng/mL). Washed platelets from untreated WT mice treated ex vivo with CS585 (10 μM) before annexin V staining and stimulation with convulxin (50 ng/mL) (n = 5). Quantification of the percentage of annexin V–positive events represent the levels of PS exposure. Data represent mean ± SEM. One-way ANOVA with Dunnett multiple comparisons. (L) WT mice treated with vehicle or CS585 (6 mg/kg) daily starting 24 hours before thrombus initiation. The venous thrombus mass was measured 2 days after inferior vena cava ligation (n = 5). Data represent mean ± SEM. Welch t-test. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.