What is the diagnosis and management for a patient with microcytic hypochromic anemia, indicated by low Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC)?

Microcytic Hypochromic Anemia: Diagnosis and Management

Primary Diagnosis: Iron Deficiency Anemia

The most likely diagnosis is iron deficiency anemia, and first-line treatment is oral ferrous sulfate 200 mg (65 mg elemental iron) three times daily for at least three months after hemoglobin normalizes to replenish iron stores. 1, 2

Diagnostic Algorithm

Initial Laboratory Evaluation

• Measure serum ferritin first as the most specific test for iron deficiency, with levels <30 μg/L indicating low body iron stores and <15 μg/L indicating absent stores 1, 2
• Use a ferritin cut-off of 45 μg/L for optimal sensitivity and specificity in clinical practice 1, 3, 2
• Check transferrin saturation (TSAT) as it is more sensitive than hemoglobin alone for detecting iron deficiency, with TSAT <16-20% supporting the diagnosis 1, 3, 2
• Evaluate red cell distribution width (RDW) to differentiate causes: low MCV with RDW >14.0% strongly suggests iron deficiency anemia, while low MCV with RDW ≤14.0% suggests thalassemia minor 1, 3, 2

Important Caveat for Inflammatory States

• In patients with elevated inflammatory markers (C-reactive protein), ferritin levels up to 100 μg/L may still indicate iron deficiency 1, 2
• Add TSAT to the workup if ferritin appears falsely elevated due to inflammation; TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease rather than iron deficiency 1

Treatment Protocol

First-Line Oral Iron Therapy

• Ferrous sulfate 200 mg (65 mg elemental iron) three times daily for at least three months after anemia correction 1, 2, 4
• Add ascorbic acid (vitamin C) to enhance iron absorption 1, 3, 2
• Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated 1, 3, 2

Expected Response

• Hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks of starting iron supplementation, confirming iron deficiency 1, 3, 2
• Continue treatment for at least 3 months after hemoglobin normalizes to replenish iron stores 1, 2

Management of Treatment Failure

If No Response Within 2-4 Weeks, Consider:

• Non-compliance or ongoing blood loss as the most common causes 1
• Malabsorption disorders (celiac disease, H. pylori infection, autoimmune atrophic gastritis) requiring switch to intravenous iron 1
• Thalassemia trait if RDW is normal or near-normal; order hemoglobin electrophoresis 1, 3
• Anemia of chronic disease if TSAT <20% with ferritin >100 μg/L and inflammatory markers present 1

Intravenous Iron Indications

• Switch to IV iron (iron sucrose or iron gluconate) if malabsorption is confirmed, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 1, 3

Investigation of Underlying Cause

Critical: Always Identify the Source of Iron Loss

• Men with hemoglobin <110 g/L and non-menstruating women with hemoglobin <100 g/L warrant fast-track gastrointestinal referral 1
• Investigation should be considered at any level of anemia with confirmed iron deficiency, especially with more severe degrees 1

Common Sources to Evaluate:

• Gastrointestinal blood loss (melena, hematochezia, occult bleeding) requiring endoscopy 1
• Menstrual blood loss in premenopausal women 1
• Malabsorption disorders (celiac disease screening if suspected) 1
• Dietary inadequacy particularly in specific populations 1

Monitoring and Follow-Up

• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then after a further year 1, 3
• Provide additional oral iron if hemoglobin or MCV falls below normal 1, 3
• Monitor for iron overload in patients receiving multiple transfusions or long-term iron therapy 1

Rare Genetic Causes to Consider

When to Suspect Genetic Disorders:

• Extreme microcytosis (MCV <70) or family history of refractory anemia 1
• Remarkably low TSAT with low-to-normal ferritin and failure to respond to oral iron (consider IRIDA - iron-refractory iron deficiency anemia) 1
• Unexplained microcytic anemia with increased TSAT (consider SLC11A2 defects) 3

Specific Genetic Conditions:

• X-linked sideroblastic anemia (ALAS2 defects): Trial of pyridoxine (vitamin B6) 50-200 mg daily initially, continuing lifelong at 10-100 mg daily if responsive 1
• IRIDA (TMPRSS6 mutations): Requires intravenous iron as oral iron is typically ineffective; monitor ferritin and avoid exceeding 500 mg/L to prevent iron overload 1
• SLC25A38 defects: Hematopoietic stem cell transplantation is the only curative option, with symptomatic treatment including transfusions and chelation 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 TSAT to the workup 1
• Do not overlook combined deficiencies such as iron deficiency coexisting with B12 or folate deficiency 1, 3
• Do not fail to investigate the source of iron loss in adults with confirmed iron deficiency, as this is essential for preventing recurrence 1