Inhibition of TF-dependent proteases and PAR-1 prevents heme-induced stasis in sickle mice. In sickle mice implanted with dorsal skinfold chambers, flowing venules were selected and mapped at baseline (20-25 venules per mouse). Mice were given a bolus infusion of stroma-free hemoglobin (SFH; 1.6 µmol/kg, IV). Percentage stasis was measured using intravital microscopy 1 hour after infusion. (A) NY1DD sickle mice were treated with control immunoglobulin G or anti-TF antibody 1H1 (25 mg/kg, intraperitoneally) 30 minutes prior to induction of stasis. (B) NY1DD mice received control chow, dabigatran (10 mg/g chow), or rivaroxaban (0.4 mg/g chow) for 4 days prior to induction of stasis. (C) NY1DD mice received saline or vorapaxar (150 µg/kg, oral gavage) once a day for 3 days prior to stasis experiments. (D) SCD/PAR1+/+ or SCD/PAR1−/− mice were infused with SFH 4 months after bone marrow transplantation. (E) The lungs of SCD/PAR1+/+ and SCD/PAR1−/− mice were excised after SFH infusion, fixed in 4% paraformaldehyde, and stained for surface pSel (green), VWF (red), and CD31 (blue). Costaining of green and red is shown as yellow. Quantification of positive pixels of VWF (scale bars, 30 μm) (F) and pSel (G) staining is represented as arbitrary units and was performed as described.9 Data are represented as mean percentage stasis + standard deviation, n = 3 to 5 mice per group. *P < .05, **P < .01, ***P < .001, 2-tailed, unpaired Student t test or 1-way analysis of variance, as appropriate.