Intramuscular cardiac hemorrhage, necrosis, and inflammatory infiltrates are uniformly associated with Cre-mediated loss of prothrombin in Mx⁺fII^lox/− mice. Representative hematoxylin/eosin-stained heart sections from a wild-type mouse (A) and Mx⁺fII^lox/− mice 4 to 6 days after poly I:C induction of hepatic Cre recombinase (B-F). Note that loss of prothrombin resulted in widespread intramuscular cardiac hemorrhage (B-F) as well as frequent subepicardial bleeding events (B,C). Large areas of the myocardium exhibited evidence of hemorrhage, infiltration of neutrophils, and ischemia/necrosis (D,E; arrows). (F) High-power view of hemorrhagic lesion with severe disruption of tissue architecture. *Ischemia/necrosis within myocardium often resulted in the formation of large acellular regions. Representative Masson trichrome-stained heart sections from a wild-type mouse (G) and Mx⁺fII^lox/− mice 4 to 6 days after poly I:C induction of hepatic Cre recombinase (H-L). In addition to focal hemorrhage, the normal cardiac structure in prothrombin-depleted mice was often disrupted by widespread areas of amorphous plasma and matrix proteins (blue regions) (H-L). (I) A high-powered view of the region in panel H illustrating free red blood cells and the disruption of the muscle fibers. (J) Hemorrhagic lesion where ischemic/necrotic myocardium has been replaced by amorphous proteinaceous exudate. (K) Areas of hemorrhage and ischemia often tracked between tissue planes to disturb large regions of the heart. (L) High-power view of the region in panel K showing hemorrhage, neutrophils, and disruption of muscle fibers. Scale bars represent 100 μm.