What is the appropriate workup and treatment for chronic low ferritin (iron) levels, also known as iron deficiency anemia?

From the Guidelines

Chronic low ferritin requires a thorough workup and treatment with oral iron supplementation as the first-line therapy, with ferrous sulfate 325 mg daily or twice daily being the standard, as recommended by the British Society of Gastroenterology guidelines 1. When evaluating a patient with chronic low ferritin, it is essential to begin with comprehensive blood tests, including complete blood count, iron studies (serum iron, total iron binding capacity, transferrin saturation), and inflammatory markers. Common causes of chronic low ferritin include:

• Inadequate dietary iron intake
• Malabsorption disorders (celiac disease, inflammatory bowel disease)
• Chronic blood loss (heavy menstruation, gastrointestinal bleeding)
• Chronic inflammation Treatment typically starts with oral iron supplementation, with ferrous sulfate 325 mg daily or twice daily being the standard first-line therapy. Alternative formulations include ferrous gluconate 300 mg or ferrous fumarate 200 mg if sulfate isn't tolerated. It is crucial to take iron supplements on an empty stomach with vitamin C to enhance absorption and avoid taking with calcium, dairy, tea, coffee, or antacids, which reduce absorption. For severe deficiency or malabsorption, intravenous iron may be necessary, with options including iron sucrose, ferric carboxymaltose, or iron dextran, as suggested by the AGA clinical practice update on management of iron deficiency anemia 1. The treatment duration typically ranges from 3-6 months to replenish iron stores, with follow-up ferritin levels checked after 2-3 months of therapy. Addressing the underlying cause is crucial for long-term management, which may involve dietary changes (increasing iron-rich foods like red meat, spinach, beans), treating malabsorption disorders, or managing chronic blood loss. Iron therapy should continue until ferritin levels normalize, typically above 50-100 ng/mL, as low ferritin can lead to fatigue, reduced exercise capacity, and cognitive impairment even without anemia, as highlighted in the ESPEN guideline on clinical nutrition in inflammatory bowel disease 1.

From the FDA Drug Label

For patients weighing 50 kg or more, the recommended dosage is: Injectafer 750 mg intravenously in two doses separated by at least 7 days for a total cumulative dose of 1,500 mg of iron per course In adult patients, Injectafer 15 mg/kg body weight up to a maximum of 1,000 mg intravenously may be administered as a single-dose per course. Administer a maintenance dose of 500 mg at 12,24 and 36 weeks if serum ferritin <100 ng/mL or serum ferritin 100-300 ng/mL with transferrin saturation <20%.

The treatment for chronic low ferritin involves administering ferric carboxymaltose (IV), with the dosage depending on the patient's weight.

• For patients weighing 50 kg or more, the recommended dosage is 750 mg intravenously in two doses separated by at least 7 days.
• In adult patients, the dosage can be 15 mg/kg body weight up to a maximum of 1,000 mg intravenously as a single-dose per course.
• A maintenance dose of 500 mg may be administered at 12,24, and 36 weeks if serum ferritin is <100 ng/mL or serum ferritin is 100-300 ng/mL with transferrin saturation <20% 2.

From the Research

Chronic Low Ferritin Workup

• The definition of iron deficiency in patients with chronic heart failure is currently being re-evaluated, with some studies suggesting that a serum ferritin level <100 ng/ml or a transferrin saturation (TSAT) <20% may not be accurate indicators of iron deficiency 3, 4.
• A more reliable indicator of iron deficiency may be a low baseline TSAT, rather than serum ferritin level, with a TSAT <20% being a more effective predictor of response to intravenous iron therapy 3, 4.
• The use of serum ferritin level <100 μg/L as a diagnostic criterion for iron deficiency may lead to the treatment of patients who are not truly iron deficient, and may ignore patients with a low TSAT but normal serum ferritin levels 3, 4.

Treatment of Iron Deficiency

• Intravenous iron therapy has been shown to be effective in reducing the risk of cardiovascular death or total heart failure hospitalization in patients with a TSAT <20% 3, 4.
• Oral iron supplementation, such as ferrous sulfate, may cause significant gastrointestinal side-effects in adults, with a meta-analysis showing an increased risk of GI side-effects compared to placebo or intravenous iron 5.
• Alternative forms of iron supplementation, such as iron bis-glycinate chelate, may be better tolerated and more effective in increasing ferritin concentration in patients with iron deficiency 6.
• The optimal treatment approach for iron deficiency may depend on the individual patient's circumstances, including the presence of chronic heart failure, kidney disease, or other comorbidities, and should be guided by a thorough diagnostic workup and consideration of the latest evidence-based guidelines 3, 4, 7.