Iron overload has been well recognized to cause oxidant-mediated cellular/tissue injury;
however, little is known about the effects of iron overload on the blood coagulation
system. We encountered an unexpected bleeding tendency in rats fed a high-iron diet in a
set of studies using iron-modified diets. In this study, we investigated the mechanism of
hemorrhagic diathesis induced by dietary iron overload in rats. Six-week-old
F344/DuCrlCrlj male rats were fed a standard (containing 0.02% iron) or a high-iron diet
(containing 1% iron) for 6 weeks and were then sampled for hematological, blood
biochemical, coagulation, and pathological examinations. Serum and liver iron levels
increased in rats fed the high-iron diet (Fe group) and serum transferrin was almost
saturated with iron. However, serum transaminase levels did not increase. Moreover, plasma
prothrombin time and activated partial thromboplastin time were significantly prolonged,
regardless of the presence of hemorrhage. The activity of clotting factors II and VII
(vitamin K-dependent coagulation factors) decreased significantly, whereas that of factor
VIII was unaltered. Blood platelet levels were not influenced by dietary iron overload,
suggesting that the bleeding tendency in iron-overloaded rats is caused by secondary
hemostasis impairment. In addition, hemorrhage was observed in multiple organs in rats fed
diets containing more than 0.8% iron. Our results suggest that iron overload can increase
the susceptibility of coagulation abnormalities caused by latent vitamin K
insufficiency.