What is the treatment for microcytic and hypochromic anemia due to iron deficiency?

Iron Profile and Treatment of Microcytic Hypochromic Anemia Due to Iron Deficiency

The first-line treatment for microcytic hypochromic anemia due to iron deficiency is oral ferrous sulfate 324 mg (65 mg elemental iron) taken one to three times daily for at least three months after hemoglobin normalizes to replenish iron stores. 1, 2

Diagnostic Iron Profile

The iron profile in iron deficiency anemia shows characteristic abnormalities that distinguish it from other causes of microcytic anemia:

• Serum ferritin <15 μg/L indicates absent iron stores, while <30 μg/L indicates low body iron stores 1, 2
• A ferritin cut-off of 45 μg/L provides optimal sensitivity and specificity for diagnosing iron deficiency in clinical practice 1, 2
• Transferrin saturation (TSAT) is low and more sensitive than hemoglobin alone for detecting iron deficiency 1, 2
• Low MCV combined with RDW >14.0% strongly suggests iron deficiency anemia, while low MCV with RDW ≤14.0% suggests thalassemia minor 1
• Serum iron is low and total iron binding capacity (TIBC) is elevated 2

Important caveat: Ferritin is an acute phase reactant and can be falsely elevated in inflammatory conditions, chronic disease, or infection despite true iron deficiency. 3 Always exclude acute inflammation by checking C-reactive protein when interpreting ferritin levels. 3

Treatment Algorithm

Step 1: Oral Iron Supplementation

Begin with ferrous sulfate 324 mg (containing 65 mg elemental iron) taken one to three times daily. 1, 2, 4 This should continue for at least three months after anemia correction to replenish iron stores. 1, 2

• Alternative oral formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate causes intolerable gastrointestinal side effects 1, 2
• Adding ascorbic acid (vitamin C) enhances iron absorption 1, 2
• A good response is defined as hemoglobin rise ≥10 g/L (≥1 g/dL) within 2 weeks, which confirms iron deficiency 1, 2
• Expected hemoglobin increase should be at least 2 g/dL within 4 weeks of starting treatment 1

Step 2: Intravenous Iron (If Oral Fails)

Consider intravenous iron if the patient has malabsorption, cannot tolerate oral iron despite trying alternative formulations, or requires rapid iron repletion. 1, 2

Common scenarios requiring IV iron include:

• Inflammatory bowel disease or celiac disease with malabsorption 2
• Chronic kidney disease 5
• Heart failure with iron deficiency 5
• Pregnancy when oral iron fails 6

Step 3: Investigate Non-Response

If hemoglobin fails to rise adequately after 4 weeks of appropriate oral iron therapy, evaluate for: 1, 2

• Ongoing blood loss (especially gastrointestinal in adults >50 years) 2, 7
• Malabsorption disorders (celiac disease, H. pylori gastritis, autoimmune atrophic gastritis) 8, 5
• Genetic disorders of iron metabolism (IRIDA due to TMPRSS6 mutations) 8, 1
• Combined deficiencies (coexisting B12 or folate deficiency) 1, 2
• Anemia of chronic disease masquerading as or coexisting with iron deficiency 2

Monitoring Protocol

Check hemoglobin, MCV, and iron studies at the following intervals: 1, 2

• 2 weeks after starting treatment to confirm response (Hb rise ≥10 g/L) 1, 2
• 4 weeks to assess adequate response (Hb rise ≥2 g/dL) 1
• 3 months after hemoglobin normalizes, then continue iron for 3 more months to replenish stores 1, 2
• Every 3 months for the first year, then annually thereafter 1, 2
• Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up 1, 2

Special Populations and Genetic Disorders

While classic iron deficiency responds to oral supplementation, rare genetic disorders present with microcytic hypochromic anemia but have different iron profiles and treatments:

Hypotransferrinemia (TF Gene Defects)

• Iron profile shows low transferrin, low TSAT, but HIGH ferritin 8
• Treatment requires transferrin supplementation via plasma transfusion or apotransferrin infusion, NOT oral iron 8

SLC11A2 (DMT1) Defects

• Iron profile shows microcytic anemia with HIGH TSAT and variable ferritin 8
• Treatment includes oral iron supplementation and/or erythropoietin and/or transfusions based on individual needs 8, 1
• Monitor for liver iron loading with MRI even when ferritin is normal 8, 1

IRIDA (TMPRSS6 Mutations)

• Iron profile shows very low TSAT, low-to-normal ferritin, and resistance to oral iron 8
• Treatment requires intravenous iron (iron sucrose or iron gluconate) as oral iron is typically ineffective 8, 1

Critical Pitfalls to Avoid

• Never continue long-term daily iron supplementation when ferritin is normal or elevated—this is potentially harmful and causes iron overload 3
• Do not miss gastrointestinal malignancy in adults with new-onset iron deficiency anemia; endoscopy is mandatory 2, 7
• Do not interpret elevated ferritin as excluding iron deficiency without checking inflammatory markers 3
• Do not overlook combined nutritional deficiencies (B12, folate) that prevent adequate response to iron alone 1, 2
• Do not assume thalassemia trait is iron deficiency; normal or low-normal RDW with very low MCV suggests thalassemia, not iron deficiency 1