What is the most likely diagnosis and appropriate management for a patient with hemoglobin 8.5 g/dL, hematocrit 28.4 %, iron 13 µg/dL, folate 3.97 ng/mL, and red blood cell count 3.47 ×10⁶/µL?

Severe Iron-Deficiency Anemia with Profound Microcytosis

This patient has severe iron-deficiency anemia requiring immediate oral iron supplementation (ferrous sulfate 200 mg once daily with vitamin C 500 mg) while simultaneously investigating the underlying cause of iron loss. 1

Diagnostic Confirmation

The laboratory profile definitively establishes iron-deficiency anemia:

• Serum iron 13 µg/dL is markedly low, confirming inadequate iron availability for erythropoiesis 1
• Hemoglobin 8.5 g/dL meets WHO criteria for moderate anemia in women (threshold <12 g/dL) 1
• RBC count 3.47 ×10⁶/µL is reduced, reflecting decreased red cell production 1
• Hematocrit 28.4% is proportionally low relative to the hemoglobin 1
• Folate 3.97 ng/mL is normal, excluding folate deficiency as a contributing cause 1

The combination of low serum iron with normal folate in the setting of anemia strongly points to iron deficiency rather than megaloblastic anemia. 1

Immediate Treatment Protocol

First-Line Oral Iron Therapy

Start ferrous sulfate 200 mg (containing ≈65 mg elemental iron) once daily immediately, without waiting for additional iron studies. 1 This is the most cost-effective first-line treatment with proven efficacy. 1

• Add vitamin C 500 mg with each iron dose to markedly enhance absorption, which is especially critical when iron stores are severely depleted 1
• Take on an empty stomach for optimal absorption; if gastrointestinal side effects occur, may take with food 1
• Once-daily dosing is superior to multiple daily doses because hepcidin remains elevated for ~48 hours after iron ingestion, blocking subsequent absorption and increasing side effects without improving efficacy 1
• If ferrous sulfate is not tolerated, ferrous fumarate (≈106 mg elemental iron) or ferrous gluconate (≈38 mg elemental iron) provide comparable efficacy 1

Expected Response and Monitoring

• Check hemoglobin at 4 weeks; expect a rise of approximately 2 g/dL (from 8.5 to ≈10.5 g/dL) 1
• A hemoglobin increase of ≥10 g/L within 2 weeks confirms iron deficiency even when baseline iron studies are incomplete 1
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores; total treatment duration is typically 6–7 months 1
• Monitor hemoglobin and red cell indices every 3 months during the first year, then again after another year 1

Critical Diagnostic Work-Up

Essential Additional Laboratory Tests

While treatment should begin immediately, the following tests must be ordered concurrently:

• Serum ferritin – the single most powerful test for confirming iron deficiency; levels <30 µg/L indicate depleted iron stores, while a cut-off of 45 µg/L provides optimal sensitivity and specificity 2
• Transferrin saturation (TSAT) – calculated as serum iron × 100 ÷ TIBC; a value <20% confirms iron deficiency 1
• C-reactive protein (CRP) – essential because ferritin is an acute-phase reactant that can be falsely elevated by inflammation, infection, malignancy, or liver disease 1
• Mean corpuscular volume (MCV) and red cell distribution width (RDW) – to morphologically classify the anemia and distinguish iron deficiency (typically RDW >14%) from thalassemia trait (RDW ≤14%) 2
• Reticulocyte count – to assess bone marrow response; a low or inappropriately normal count in anemia indicates inadequate production 3

Interpretation Framework

• If ferritin <30 µg/L: iron deficiency is confirmed 2
• If ferritin 30–100 µg/L with TSAT <20%: suggests combined iron deficiency and anemia of chronic disease 1
• If ferritin >100 µg/L with TSAT <20% and elevated CRP: indicates anemia of chronic disease with functional iron deficiency 1

Investigation of Underlying Cause

Iron deficiency in adults always requires investigation for the source of iron loss; treatment with iron supplementation alone without identifying the cause is inadequate. 1

For Premenopausal Women (Most Likely Scenario)

• First assess menstrual blood loss – menorrhagia, pregnancy, and breastfeeding account for iron deficiency in 5–10% of menstruating women 1
• Screen for celiac disease with tissue transglutaminase IgA antibodies and total IgA; celiac disease is present in 3–5% of iron-deficiency cases and can cause treatment failure if missed 1
• Test for Helicobacter pylori using stool antigen or urea-breath test 1
• Reserve bidirectional endoscopy (upper endoscopy with duodenal biopsies + colonoscopy) for patients who:
  • Are ≥50 years old 1
  • Have gastrointestinal symptoms (abdominal pain, altered bowel habits, overt bleeding) 1
  • Have positive celiac or H. pylori testing requiring confirmation 1
  • Fail to respond to adequate oral iron after 8–10 weeks 1
  • Have a strong family history of colorectal cancer 1

For Men or Postmenopausal Women

• Urgent bidirectional endoscopy is mandatory because iron deficiency may be the sole manifestation of gastrointestinal malignancy 1
• Upper endoscopy with duodenal biopsies screens for celiac disease, gastric cancer, peptic ulcer disease, and NSAID-induced gastropathy 1
• Colonoscopy detects colonic carcinoma, adenomatous polyps, angiodysplasia, and inflammatory bowel disease 1

When to Switch to Intravenous Iron

Consider IV iron if oral therapy fails or specific contraindications exist: 1

• Intolerance to ≥2 different oral iron formulations (ferrous sulfate, fumarate, or gluconate) 1
• Ferritin does not improve after 4 weeks of compliant oral therapy 1
• Active inflammatory bowel disease with hemoglobin <10 g/dL (hepcidin-mediated absorption blockade) 1
• Post-bariatric surgery patients (duodenal absorption disrupted) 1
• Celiac disease with inadequate response despite strict gluten-free diet adherence 1
• Ongoing gastrointestinal blood loss that exceeds the replacement capacity of oral iron 1

Preferred IV Iron Formulations

• Ferric carboxymaltose: 750–1000 mg per 15-minute infusion; two doses ≥7 days apart provide ≈1500 mg total 1
• Ferric derisomaltose: 1000 mg as a single infusion 1
• Avoid iron dextran as first-line due to higher anaphylaxis risk (≈0.6–0.7%) 1
• All IV iron must be administered in a setting equipped with resuscitation facilities 1

Critical Pitfalls to Avoid

• Do not prescribe multiple daily oral doses – this increases side effects without added benefit because hepcidin blocks subsequent absorption 1
• Do not discontinue iron therapy when hemoglobin normalizes – continue for an additional 3 months to restore stores 1
• Do not persist with oral iron beyond 4 weeks without a hemoglobin rise – reassess for malabsorption, ongoing loss, or need for IV iron 1
• Do not overlook vitamin C supplementation when oral iron response is suboptimal 1
• Do not delay investigation of the underlying cause – gastrointestinal malignancy may present solely with iron deficiency 1
• Do not assume all microcytic anemia is iron deficiency – anemia of chronic disease, thalassemia, and sideroblastic anemia require different management 2

Special Considerations

If Reticulocyte Count is Low

A low reticulocyte count in the setting of anemia indicates inadequate bone marrow response and requires evaluation for: 3

• Nutritional deficiencies (iron, vitamin B12, folate) 3
• Anemia of chronic disease or inflammation 3
• Chronic kidney disease (insufficient erythropoietin production) 3
• Primary bone marrow failure or myelodysplastic syndrome 3

If Patient Has Inflammatory Markers

• In the presence of inflammation, ferritin up to 100 µg/L may still represent true iron deficiency 1
• TSAT <20% confirms iron-deficient erythropoiesis even when ferritin appears normal 1
• Treat the underlying inflammatory condition as the primary intervention while providing iron supplementation 1