What is the appropriate diagnosis and treatment for iron deficiency anemia with low hemoglobin, low MCV, and low MCHC?

Diagnosis and Management of Microcytic Hypochromic Anemia

Immediate Diagnostic Approach

The combination of low hemoglobin, low MCV, and low MCHC indicates microcytic hypochromic anemia, most commonly iron deficiency anemia, which requires serum ferritin measurement as the primary diagnostic test and oral iron supplementation as first-line treatment. 1, 2

Essential Laboratory Workup

• Serum ferritin is the most powerful diagnostic test for iron deficiency, with levels <12 μg/dL being diagnostic of iron deficiency in the absence of inflammation 1, 2
• In patients with concurrent inflammation, malignancy, or hepatic disease, ferritin up to 100 μg/L may still indicate iron deficiency 1, 2
• Complete blood count with red cell distribution width (RDW) helps differentiate causes: elevated RDW (>14.0%) with microcytosis strongly suggests iron deficiency anemia 1, 3, 2
• Transferrin saturation <30% supports the diagnosis when ferritin results are equivocal 1, 2
• Reticulocyte count should be measured: low or normal reticulocytes indicate deficiency states rather than hemolysis 1

Critical Differential Diagnosis

Before assuming iron deficiency, rule out thalassemia trait, especially in patients with:

• Very high RBC count (>4.4 × 10⁶/μL) combined with very low MCV (<69 fL), which has 92.9% sensitivity and 100% specificity for thalassemia syndromes 4
• Appropriate ethnic background (Mediterranean, Southeast Asian, African descent) 1, 2
• Hemoglobin electrophoresis should be performed to diagnose β-thalassemia trait when suspected 1, 3, 2

Do not overlook combined deficiencies: iron deficiency can coexist with folate or B12 deficiency, which may mask microcytosis and present with elevated RDW 1, 3, 2

Treatment Protocol

Oral Iron Supplementation (First-Line)

Prescribe ferrous sulfate 324 mg (65 mg elemental iron) three times daily for at least three months after correction of anemia to replenish iron stores 3, 2, 5

• Adding ascorbic acid (vitamin C) enhances iron absorption 3
• For children: prescribe 3 mg/kg per day of elemental iron administered between meals 1
• A good response is defined as hemoglobin rise ≥1 g/dL (or ≥10 g/L) within 2-4 weeks, which confirms the diagnosis 1, 3, 2

When Oral Iron Fails

If anemia does not respond after 4 weeks despite compliance:

• Consider intravenous iron for malabsorption or intolerance, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 3, 2, 6, 7
• Perform extended workup including vitamin B12, folate, haptoglobin, and consider hematology referral 1
• Re-evaluate for genetic disorders of iron metabolism or heme synthesis 1, 3

Mandatory Investigation for Underlying Cause

Gastrointestinal Evaluation (Essential in Adults)

All adult men and postmenopausal women with confirmed iron deficiency anemia require complete gastrointestinal investigation to exclude occult malignancy 1, 2

• Upper GI endoscopy with small bowel biopsies should be performed first, as 2-3% of patients have celiac disease 1, 3, 2
• Lower GI tract examination (colonoscopy preferred) is mandatory unless upper endoscopy reveals carcinoma or celiac disease, as dual pathology occurs in 10-15% of patients 1, 2
• Document and discontinue NSAIDs, aspirin, and anticoagulants when possible 1, 2

Premenopausal Women

• Screen all for celiac disease with small bowel biopsies during endoscopy 1, 2
• Further GI investigation should be based on clinical judgment, symptoms, and risk factors 2
• Do not accept menstrual blood loss as the sole cause without appropriate evaluation 2

Monitoring and Follow-Up

• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then after a further year 3, 2
• Provide additional oral iron if hemoglobin or MCV falls below normal 3
• Continue iron supplementation for 2-3 months after anemia correction to replenish body stores 3, 2, 6
• Reassess approximately 6 months after successful treatment completion 1

Critical Pitfalls to Avoid

• Never accept dietary history alone as the cause without completing full GI investigation in adults 1, 2
• Do not assume normal hemoglobin excludes iron deficiency: hypochromic microcytic changes precede anemia development 3
• Never overlook the 7-9% of patients with both thalassemia trait and iron deficiency: check ferritin even when thalassemia is diagnosed 3, 4
• Do not accept minor upper GI findings (erosions, peptic ulcer) as the sole cause without completing lower GI evaluation 2
• Fecal occult blood testing is of no benefit in the investigation of iron deficiency anemia 2