What is the appropriate diagnosis and treatment approach for a patient presenting with microcytic hypochromic anemia?

Microcytic Hypochromic Anemia: Diagnosis and Treatment

Immediate Diagnostic Workup

Start with serum ferritin as the single most specific test for iron deficiency, using a cutoff of 45 μg/L for optimal sensitivity and specificity, with levels <30 μg/L indicating low body iron stores. 1

• Measure transferrin saturation (TSAT) alongside ferritin, as it is more sensitive than hemoglobin alone for detecting iron deficiency 2, 1
• A TSAT <16-20% confirms iron deficiency, while TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease 1
• In inflammatory states, ferritin up to 100 μg/L may still represent iron deficiency due to false elevation 1
• Check red cell distribution width (RDW): an elevated RDW (>14.0%) with low MCV strongly points toward iron deficiency rather than thalassemia trait, which typically presents with RDW ≤14.0% 2, 1

Differential Diagnosis Algorithm

The combination of CBC indices guides your differential:

• Iron deficiency anemia: Low MCV + elevated RDW (>14%) + low ferritin (<45 μg/L) + low TSAT (<20%) 2, 1
• Thalassemia trait: Low MCV (often <70 fL) + normal RDW (≤14%) + normal/elevated ferritin + normal iron studies 1, 3
• Anemia of chronic disease: Low/normal MCV + TSAT <20% + ferritin >100 μg/L + inflammatory markers present 1
• Genetic iron disorders: Extremely low MCV (<70 fL) + low-normal ferritin (>20 μg/L) + failure to respond to oral iron 4, 1

First-Line Treatment for Iron Deficiency Anemia

Prescribe ferrous sulfate 324 mg (65 mg elemental iron) three times daily for at least three months after anemia correction to replenish iron stores. 2, 1, 5

• Add ascorbic acid (vitamin C) to enhance iron absorption 2
• Alternative formulations include ferrous gluconate or ferrous fumarate if gastrointestinal side effects are intolerable 2, 1
• A good response is defined as hemoglobin rise ≥10 g/L (≥1 g/dL) within 2 weeks, which confirms iron deficiency 2, 1
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks of treatment 2, 1

When Oral Iron Fails

If no response within 2-4 weeks, consider these causes systematically:

• Non-compliance or ongoing blood loss (most common) 1
• Malabsorption disorders: celiac disease, H. pylori infection, autoimmune atrophic gastritis 1
• Switch to intravenous iron (iron sucrose or iron gluconate) if malabsorption confirmed, expecting hemoglobin increase of at least 2 g/dL within 4 weeks 2, 1
• IRIDA (iron-refractory iron deficiency anemia): remarkably low TSAT with low-normal ferritin, autosomal recessive TMPRSS6 mutations, requires IV iron as oral is ineffective 1

Investigation of Underlying Cause

All adults with confirmed iron deficiency require investigation for the source of iron loss. 1

• Men with Hb <110 g/L or non-menstruating women with Hb <100 g/L warrant fast-track gastrointestinal referral 1
• Consider investigation at any level of anemia with confirmed iron deficiency, especially with severe degrees 1
• Evaluate for gastrointestinal blood loss (melena, hematochezia, occult bleeding), menstrual blood loss in premenopausal women, dietary inadequacy, or malabsorption 1
• Screen for celiac disease if malabsorption suspected 1

Genetic Disorders Requiring Alternative Management

If ferritin is normal/elevated (>20 μg/L) despite microcytosis, or extreme microcytosis (MCV <70 fL) present, consider genetic disorders:

• Order hemoglobin electrophoresis if microcytosis with normal iron studies or MCV disproportionately low relative to anemia degree 1
• X-linked sideroblastic anemia (ALAS2 defects): trial of pyridoxine (vitamin B6) 50-200 mg daily initially, then maintenance 10-100 mg daily lifelong if responsive 4, 1
• SLC11A2 (DMT1) defects: oral iron supplementation may increase hemoglobin and achieve transfusion independence 4
• SLC25A38 defects: hematopoietic stem cell transplantation is the only curative option; symptomatic treatment includes transfusions and chelation 4, 1
• IRIDA (TMPRSS6 defects): intravenous iron (iron sucrose or iron gluconate) required, as oral iron typically ineffective 1

Monitoring Protocol

• Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year, then after a further year 2, 1
• Provide additional oral iron if hemoglobin or MCV falls below normal 2, 1
• For patients receiving multiple transfusions or long-term iron therapy, monitor for iron overload 1
• Consider MRI of the liver in specific cases to detect toxic iron loading early 1

Critical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency: anemia of chronic disease, thalassemia, and sideroblastic anemia require different management 1
• Do not use ferritin alone in inflammatory states, as it can be falsely elevated; add transferrin saturation to the workup 1
• Do not overlook combined deficiencies: iron deficiency can coexist with B12 or folate deficiency 1
• Do not fail to investigate the source of iron loss in adults with confirmed iron deficiency, as this may reveal serious underlying pathology including malignancy 1