E15.5 sagittal sections of Tfpi−/−brains at the level of the interpeduncular fossa displayed large areas of cellular death and associated hemorrhage surrounded by vascular anomalies called glomeruloid bodies. (A) H&E staining shows that the Tfpi+/+ brain fills the entire cavity of the skull, while the Tfpi−/− brain is smaller and underdeveloped, with a large space between the brain and the calvarium. Arrows identify enlarged congested blood vessels in the Tfpi−/− brain (scale bars, 100 µm). IPF, interpeduncular fossa. (B) High magnification of the enlarged congested vessels in the Tfpi−/− brain identified them as glomeruloid bodies (scale bars, 30 µm). H&E: a multicompartmental vessel with pink amorphous material suggestive of fibrin clot and lumens containing nucleated RBCs. Trichrome (TRI): a multicompartmental vessel with septa containing collagen and nucleated RBCs within the lumens. MSB: a multicompartmental vessel containing numerous yellow nucleated RBCs and pink to red fibrin lining the lumens. (C) MSB staining highlighted the brain pathology of Tfpi−/− embryos. The dotted black line encircles a large area of cell death (pyknotic nuclei and loss of parenchyma) and hemorrhage (pools of yellow-stained nucleated RBCs). Arrows identify numerous glomeruloid bodies surrounding the area of necrosis and hemorrhage (scale bar, 100 µm).