Fig. 6: MPI 8 does not induce bleeding in mice.

A–C High doses of the lead MPI candidate do not cause bleeding in mice. A Schematic representation of mouse tail bleeding model with C57/BL6 mice. B Recorded bleeding time. Mice were injected in a blinded study with up to 300 mg/kg of lead MPI candidates and demonstrated no increase in bleeding side effect, in contrast to mice administered 200 U/kg of unfractionated heparin. C Hemoglobin lost by mice. D–F MPI 8 did not decrease platelet recruitment and fibrin formation in hemostatic clot formation assessed via saphenous vein hemostasis model. Quantitative analysis of the dynamics of platelet accumulation (D) and fibrin formation (E) in response to vascular injury in saphenous vein. The kinetic curves represent the mean fluorescence intensity, and the shaded regions are representative of the standard error (SEM). F Representative images of platelet (green) and fibrin (red) hemostatic clot formation in response to a repetitive vascular injury of the saphenous vein. Mice were injected with 200 mg/kg of the lead MPI 8 candidate. The scale bar is 100 µm shown in the left lower corner of the composite image of panel 3 (third from left) for wild type (control) and treated (MPI 8) groups. All results represent mean values +/− SD of n = 8 mice per group. Results analyzed using ordinary one-way ANOVA, two-tailed, with Tukey’s multiple comparisons test. ****P < 0.0001, ns not significant. Figure 6A was created with using BioRender.com.