What are the next steps for a patient with normal iron and ferritin levels but low iron saturation?

From the Guidelines

For a patient with normal iron and ferritin levels but low iron saturation, the next steps should include further diagnostic evaluation to determine the underlying cause, considering the most recent guidelines from 2023 1. The patient's low iron saturation despite normal iron and ferritin levels could indicate early iron deficiency before stores are depleted, chronic disease, or increased iron binding capacity.

• Consider ordering a complete blood count (CBC) to check for anemia and a total iron binding capacity (TIBC) test to assess transferrin levels, as these tests will help determine if the low saturation is due to early iron deficiency, chronic inflammation, or other conditions.
• If inflammation is suspected, check C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), as the presence of inflammation can affect the interpretation of ferritin levels, with a serum ferritin up to 100 mg/L potentially still consistent with iron deficiency in the presence of inflammation 1.
• In the absence of anemia or symptoms, watchful waiting with repeat testing in 3-6 months may be appropriate, but for patients with symptoms like fatigue, a trial of oral iron supplementation, such as ferrous sulfate 325 mg daily or every other day, might be considered, taken with vitamin C to enhance absorption and between meals to avoid interference from food.
• Investigate potential causes of occult blood loss, such as gastrointestinal bleeding or heavy menstrual periods in women of reproductive age, as these can contribute to iron deficiency.
• According to the 2023 guidelines, intravenous iron should be considered as first-line treatment in patients with clinically active disease, previous intolerance to oral iron, hemoglobin below 100 g/L, and in patients who need erythropoiesis-stimulating agents, while oral iron may be used in patients with mild anemia and clinically inactive disease 1.

From the Research

Next Steps for Patients with Normal Iron and Ferritin but Low Iron Saturation

• The patient's condition, characterized by normal iron and ferritin levels but low iron saturation, may indicate a complex iron deficiency status that requires careful evaluation 2.
• According to a study published in the International Journal of Chronic Diseases, patients with inflammatory conditions may have restricted iron availability despite normal or high serum ferritin levels, and transferrin saturation (TSAT) should also be assessed to confirm iron deficiency 2.
• A threshold of TSAT < 20% can be considered diagnostic for iron deficiency in certain conditions, and routine surveillance of serum ferritin and TSAT is advisable in at-risk groups 2.
• Treatment of underlying diseases is recommended along with iron supplementation, and oral iron supplements are the first choice, while intravenous iron may be considered in certain cases 3.
• The use of a food supplement containing nutrients that improve iron bioavailability may be a valid alternative to iron therapy, as shown in a study published in Minerva Medica 4.
• Iron therapy can lead to an improvement in blood iron and ferritin levels, but the effect on serum ferritin levels may vary depending on the dose and duration of treatment, as noted in a study published in Blood 5.
• Further evaluation and monitoring of the patient's condition are necessary to determine the best course of treatment and to assess the response to therapy 6, 3, 2.