What is the diagnosis for a patient with low iron saturation (Iron Sat), elevated transferrin and total iron-binding capacity (TIBC), and decreased ferritin levels?

From the Guidelines

The laboratory findings of low iron saturation, high transferrin, high iron binding capacity, and low ferritin strongly indicate iron deficiency anemia, and I recommend starting oral iron supplementation immediately. According to the study by G. Van Assche et al. 1, a serum ferritin level < 30 mcg/L or transferrin saturation < 16% define iron deficiency in patients without any evidence of inflammation. In this case, the low ferritin and low iron saturation levels suggest iron deficiency anemia.

Key Considerations

• The study suggests that in the absence of biochemical or clinical inflammation, ferritin is a reliable indicator of iron storage levels, and a serum ferritin level < 15 μg/L indicates absolute iron deficiency 1.
• The transferrin saturation level below 16% is also a sensitive marker of iron deficiency, although it has a low specificity of only 40–50% 1.
• To confirm the diagnosis, measurements of inflammatory parameters that are independent of iron metabolism (ESR, CRP) should be carried out to aid diagnosis 1.

Treatment Recommendations

• I recommend starting oral iron supplementation, typically ferrous sulfate 325 mg (containing 65 mg elemental iron) taken 1-2 times daily on an empty stomach.
• For better absorption, take iron with vitamin C (such as orange juice) and avoid taking it with calcium, dairy, coffee, tea, or antacids which can reduce absorption.
• Treatment should continue for at least 3-6 months to replenish iron stores completely, even after hemoglobin normalizes.
• Common side effects include constipation, nausea, and black stools.
• If oral iron isn't tolerated, consider iron polysaccharide complex or, in severe cases, intravenous iron formulations like iron sucrose or ferric carboxymaltose.

Follow-up and Monitoring

• Follow-up testing of iron studies and complete blood count should be done after 4-8 weeks of treatment to monitor response.
• It's essential to identify and address the underlying cause of iron deficiency, which may include blood loss (menstrual, gastrointestinal), poor dietary intake, malabsorption disorders, or increased iron requirements during pregnancy.

From the Research

Iron Deficiency Diagnosis and Treatment

• Low iron saturation, high transferrin, and iron binding capacity with low ferritin levels are indicative of iron deficiency 2.
• Iron deficiency can be diagnosed by low serum ferritin (typically <30 ng/mL) in individuals without inflammatory conditions or by transferrin saturation (iron/total iron binding capacity × 100) less than 20% 2.
• The most common causes of iron deficiency are bleeding (menstrual, gastrointestinal), impaired iron absorption (atrophic gastritis, celiac disease, bariatric surgical procedures), inadequate dietary iron intake, and pregnancy 2.

Treatment Options

• Oral iron (ferrous sulfate 325 mg/d or on alternate days) is typically first-line therapy for iron deficiency 2.
• Intravenous iron is indicated for patients with oral iron intolerance, poor absorption (celiac disease, post-bariatric surgical procedure), chronic inflammatory conditions (CKD, HF, IBD, cancer), ongoing blood loss, and during the second and third trimesters of pregnancy 2, 3.
• Alternate-day administration of oral iron supplements may increase iron absorption compared to consecutive-day iron administration 4.
• Lactoferrin supplementation has been shown to have better effects on serum iron, ferritin, and hemoglobin concentration compared to ferrous sulfate, but with a reducing effect on fractional iron absorption 5.

Considerations

• Intravenous iron therapy is associated with a risk of severe infusion reactions and hypophosphatemia 3.
• The choice of iron supplement and dosing schedule should be individualized based on the patient's needs and response to treatment 2, 4.
• It is essential to identify and treat the underlying cause of iron deficiency to prevent recurrence 2.