Sickle chimeras with genetically reduced FII levels have improved hepatic morphology, function, and reduced vascular occlusions. Representative H&E liver sections from HbS/FII^WT (left panel, A-D) and HbS/FII^lox/− (right panel, A-D) mice 1 year following marrow transplant viewed at various magnifications (objectives: A, ×10; B, ×20; C, ×40; and D, ×60) showing multifocal areas of coagulative hepatic necrosis with occasionally associated massively congested blood vessels (shown by arrows in panel C) in HbS/FII^WT mice. Areas of necrosis are marked by dotted lines (A-B,D) and infiltrating leukocytes are marked by arrowheads (D) in HbS/FII^WT mice. In HbS/FII^lox/− mice, the areas of coagulative necrosis were minimal with comparatively fewer congested blood vessels seen. (F-H) CD31 staining of liver vascular endothelial cells showing vascular congestion in HbS/FII^WT mice (shown by arrows) along with prominent rounded endothelial cells (H). These changes were minimal in HbS/FII^lox/− mice. No differences were observed in the microvascular density (MVD) in liver sections from HbA/FII^WT and HbA/FII^lox/− mice. (F-G) Objective, ×40. (H) Objective, ×100. Images are representative of 9 mice per experimental group. (E) Alanine transaminase (ALT) activity in the serum of HbS/FII^WT, HbS/FII^lox/−, HbA/FII^WT, and HbS/FII^lox/− mice. Each symbol represents an individual animal and lines represent median values. Mice used as transplant recipients were of similar ages (8-10 weeks) with equal numbers of males and females distributed among the experimental groups. Fully chimeric sickle or normal mice were followed for a year after transplantation. Cohorts were analyzed by Mann-Whitney U test and statistical significance between FII^WT and FII^lox/− chimeras is indicated by asterisks: *P < .05. n.s., not significant.