I have iron deficiency anemia with serum iron 26 µg/dL, ferritin 9.2 ng/mL, transferrin saturation 7.9%, total iron‑binding capacity 331 µg/dL while taking ferrous sulfate 325 mg daily; what is the next step in management?

Management of Inadequate Response to Oral Iron in Iron Deficiency Anemia

You should switch to intravenous ferric carboxymaltose because your laboratory values demonstrate severe iron deficiency (ferritin 9.2 ng/mL, transferrin saturation 7.9%) that has failed to respond adequately to daily oral ferrous sulfate 325 mg, meeting established criteria for IV iron therapy. 1

Why Oral Iron Has Failed in Your Case

Your current regimen is suboptimal for several reasons:

• Daily dosing blocks subsequent absorption: Taking ferrous sulfate 325 mg (65 mg elemental iron) every day elevates hepcidin levels for up to 24 hours, reducing iron absorption by 35–45% on subsequent doses. 1

• Your iron stores are critically depleted: A ferritin of 9.2 ng/mL is far below the 30 ng/mL threshold that confirms absolute iron deficiency, and your transferrin saturation of 7.9% is markedly below the 16% diagnostic cutoff for iron deficiency in adults. 2, 3

• Absorption capacity is overwhelmed: Even optimal oral iron absorption cannot match the rate of depletion when stores are this low, particularly if you have ongoing blood loss or malabsorption. 1

Immediate Next Steps: Switch to Intravenous Iron

Intravenous ferric carboxymaltose is indicated because you meet multiple criteria for IV therapy:

• Lack of adequate hematologic response after taking oral iron (your ferritin remains critically low at 9.2 ng/mL despite daily supplementation). 1, 2

• Transferrin saturation of 7.9% indicates severely impaired iron delivery to bone marrow, far below the 20% target needed for adequate erythropoiesis. 2, 3

Dosing and administration:

• Ferric carboxymaltose 15 mg/kg body weight (maximum 750–1,000 mg per infusion) administered on two occasions separated by at least 7 days, up to a cumulative dose of 1,500 mg. 4

• This regimen produces reticulocytosis within 3–5 days and increases hemoglobin by approximately 1.6–2.9 g/dL within 4–5 weeks. 4, 5

• Mean ferritin rises by 218–269 ng/mL and transferrin saturation increases by 9–20% within 4–8 weeks. 4, 5

Mandatory Diagnostic Workup (Concurrent with IV Iron)

You must identify the underlying cause of your iron deficiency:

For All Patients

• Screen for celiac disease: Order tissue transglutaminase IgA testing, as celiac disease accounts for 3–5% of iron deficiency cases and causes treatment failure when missed. 3

• Test for Helicobacter pylori: Use stool antigen or urea breath testing, because this organism impairs intestinal iron absorption. 3

• Assess dietary intake: Identify low heme-iron consumption, especially in vegetarian or vegan diets, as non-heme iron is poorly absorbed. 2

Gender- and Age-Specific Evaluation

• If you are a premenopausal woman: First assess for heavy menstrual bleeding (soaking through a pad or tampon every 1–2 hours, or periods lasting >7 days), which is the most common cause in this population. 2, 3

• If you are a man or postmenopausal woman: Bidirectional endoscopy (upper gastroscopy plus colonoscopy) is mandatory, as iron deficiency may be the sole manifestation of gastrointestinal malignancy. 2, 3, 6

• Red-flag features requiring endoscopy in premenopausal women: Age ≥50 years, gastrointestinal symptoms (abdominal pain, altered bowel habits, visible blood in stool), positive celiac or H. pylori testing, lack of hemoglobin response after 8–10 weeks of adequate oral iron, or strong family history of colorectal cancer. 3

Additional Testing

• Complete blood count with differential: Evaluate for microcytosis, hypochromia, and abnormal white blood cell counts that may indicate a myeloproliferative disorder. 3

• Urinalysis: Detect hematuria or proteinuria as possible sources of chronic iron loss. 3

• Renal function (serum creatinine, eGFR): Chronic kidney disease contributes to both iron deficiency and anemia through multiple mechanisms. 2

Treatment Targets After IV Iron Repletion

Aim for the following laboratory goals:

• Ferritin ≥100 ng/mL to ensure sufficient iron stores and prevent recurrence. 2, 3

• Transferrin saturation ≥20% to confirm adequate iron availability for erythropoiesis. 2, 3

• Hemoglobin ≥12 g/dL (adult females) or ≥13 g/dL (adult males) to consider anemia corrected. 2

Monitoring Schedule

• Repeat iron studies and complete blood count 4–8 weeks after the last IV iron infusion. Do not measure iron parameters within 4 weeks of IV iron administration, as circulating iron can falsely elevate results. 2, 3

• If you return to oral iron after IV repletion: Use alternate-day dosing (every other day) with 50–100 mg elemental iron on an empty stomach, which improves fractional absorption by 30–50% and reduces gastrointestinal side effects. 1, 2, 3

• Continue supplementation for 3 months after hemoglobin normalizes to achieve ferritin >100 ng/mL and prevent rapid recurrence. 3

• Schedule ferritin screening every 6–12 months to detect early depletion before anemia develops, especially if you have ongoing risk factors (menstruation, vegetarian diet, endurance athletics). 1, 3

Critical Pitfalls to Avoid

• Do not continue oral iron indefinitely without reassessment: Lack of response after 4–8 weeks warrants evaluation for malabsorption, ongoing loss, or transition to IV iron. 2, 3

• Do not rely on "normal" serum iron to exclude deficiency: Serum iron shows high day-to-day variability and is affected by recent meals, diurnal changes, and inflammation; ferritin and transferrin saturation are far more reliable. 1, 2

• Do not discontinue iron therapy once hemoglobin normalizes: An additional 3 months of supplementation is required for ferritin to reach >100 ng/mL. 3

• Do not delay endoscopic evaluation in men or postmenopausal women: Gastrointestinal malignancy can present solely with iron deficiency. 3, 6

• Do not overlook celiac disease screening: Its 3–5% prevalence among iron-deficiency cases means missed diagnosis leads to treatment failure. 3