Iron is decreased due to decreased release of Fe from macrophages into the plasma. Ferritin, an acute phase reactant, may be elevated in inflammatory conditions. The definitive test for iron deficiency is a Prussian blue stained bone marrow. The upper image demonstrates an absence of iron in the bone marrow macrophages of an individual with iron deficiency. Compare the upper image with the lower image of a normal bone marrow stained with Prussian blue and demonstrating coarse granular storage iron in macrophages.
Iron deficiency develops gradually.
Storage iron in the bone marrow is the first to become depleted. Later, synthesis of hemoglobin becomes impaired by the lack of iron and readily recognizable anemia results. Eventually iron is lost from tissues other than blood including the liver, skin and skeletal muscle. As a result the RBCs tend to vary in size. In thalassemia, each erythrocyte has the same genetic defect, each makes the same reduced amount of hemoglobin and so each RBC is about the same size.