After intravenous iron administration, serum ferritin often rises sharply for several days. This is not a reflection of iron overload but rather the expected physiologic handling of IV iron by the reticuloendothelial system:
- Iron uptake by macrophages:
IV iron complexes (e.g., iron dextran, ferric carboxymaltose) are taken up by macrophages of the liver, spleen, and bone marrow. - Intracellular ferritin synthesis:
Within macrophages, iron is stored in ferritin molecules — an immediate buffering response to the sudden influx of elemental iron. - Ferritin release into plasma:
Some ferritin is secreted into circulation, leading to a transient rise in serum ferritin levels.
Meanwhile, hepcidin increases, reducing iron export through ferroportin. As a result, transferrin saturation (TSAT) remains in the normal range despite the ferritin spike. Over the following weeks, iron is slowly released from macrophages and incorporated into erythropoiesis, and ferritin levels gradually decline toward a new steady state.
