FXII contributes to vascular stasis and congestion in HbSS mice. (A) Townes HbSS mice were implanted with dorsal skinfold chambers. Using intravital microscopy, between 20 and 25 subcutaneous venules were selected and mapped. Mice were treated with IgG or 15D10 (10 mg/kg, IV) 30 minutes before challenge with stroma-free Hb (1 μmol/kg, IV). The preselected venules were marked as flowing or static at 1, 2, 3, and 4 hours after Hb infusion, and the percentage static venules was calculated. n = 4 mice per group, data represent mean ± SEM. ∗∗∗∗P < .0001 vs IgG/SS at each time point by two-way ANOVA. Paraffin sections of livers and kidneys from AA/FXII^+/+, AA/FXII^−/−, SS/FXII^+/+, and SS/FXII^−/− mice 4 months after BM transplantation were stained with hematoxylin and eosin. (B) Sinusoidal congestion and (C) glomerular congestion were scored by blinded pathologists. Representative images are shown; n = 4 to 8 mice per group, data represent mean ± SEM. ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001 by two-way ANOVA and Tukey post-hoc test. Asterisks above bar represent difference from HbAA, asterisks above line indicate difference between FXII genotype. Red staining on representative images showed in panels B and C demonstrates presence of RBC within congested vessels. ANOVA, analysis of variance.