What is the appropriate diagnosis and treatment for a patient with anemia, hypohemoglobinemia, and hypohematocritemia?

Normocytic Anemia with Hypochromia: Diagnostic Workup and Treatment

This patient has anemia (Hb 9.8 g/dL) with a normal MCV (94.5 fL) but low MCHC (31.4), indicating hypochromic normocytic anemia, which most commonly represents early or evolving iron deficiency anemia that requires immediate iron studies and targeted iron replacement therapy. 1, 2

Immediate Diagnostic Workup Required

The minimum essential tests to determine the cause and guide treatment include: 3

• Serum ferritin (most specific test for iron deficiency; <30 μg/L indicates iron deficiency, though <45 μg/L provides optimal sensitivity/specificity) 1, 4, 2
• Transferrin saturation (TSAT) (more sensitive than hemoglobin alone; <20% indicates iron deficiency) 1, 4, 2
• C-reactive protein (CRP) (to identify inflammation that may elevate ferritin falsely) 3
• Reticulocyte count (low/normal suggests inadequate bone marrow response; elevated suggests hemolysis or blood loss) 3, 5

Additional Testing Based on Initial Results

If ferritin is normal or elevated (>20 μg/L) despite the hypochromic picture, consider genetic disorders of iron metabolism rather than simple iron deficiency. 4, 2

For more extensive workup if the cause remains unclear: vitamin B12, folate, haptoglobin, lactate dehydrogenase, and peripheral blood smear evaluation. 3

Most Likely Diagnosis

Iron deficiency anemia is the most probable diagnosis given: 1, 2, 5

• Low hemoglobin (9.8 g/dL in a female if this patient is female; <12.0 g/dL threshold) 3, 6
• Hypochromia (MCHC 31.4, below normal 32-36 g/dL) indicating reduced hemoglobin concentration per red cell 2
• Normal RDW (13.5%) does not exclude iron deficiency, though elevated RDW >14.0% would strengthen the diagnosis 1, 4, 2
• Normal MCV suggests early iron deficiency before microcytosis develops 4, 7

Critical Pitfall to Avoid

Do not assume normal hemoglobin excludes iron deficiency—hypochromic changes precede anemia development and normocytic indices can occur in early iron deficiency. 4, 7

Treatment Algorithm

First-Line Treatment (Pending Iron Studies)

Oral iron supplementation with ferrous sulfate 200 mg (65 mg elemental iron) three times daily for at least 3 months after anemia correction to replenish iron stores. 1, 4, 2

• Add ascorbic acid (vitamin C) to enhance iron absorption 1, 4, 2
• Alternative formulations (ferrous gluconate or ferrous fumarate) if gastrointestinal side effects are intolerable 2

Expected Response and Confirmation

• Good response = hemoglobin rise ≥10 g/L (≥1 g/dL) within 2 weeks, confirming iron deficiency 1, 4, 2
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks 4, 2
• Repeat CBC after 4-8 weeks to assess response 1

If No Response to Oral Iron

Consider intravenous iron if: 4

• Malabsorption is present
• Oral iron is not tolerated
• No hemoglobin response after 4 weeks

Monitoring Schedule

• Hemoglobin and red cell indices at 3-month intervals for 1 year, then after another year 1, 4, 2
• Provide additional oral iron if hemoglobin or MCV falls below normal 4, 2

Investigation of Underlying Cause

In adult men and post-menopausal women, gastrointestinal evaluation is mandatory as GI blood loss is the most common cause: 1

• Upper endoscopy and colonoscopy to exclude GI malignancy 1
• Consider small bowel biopsy during endoscopy to rule out celiac disease 1

In premenopausal women, menstrual blood loss is the most common cause, but persistent anemia despite treatment warrants GI evaluation. 1

Common Pitfalls and Caveats

• Serum ferritin can be falsely elevated in inflammatory states (infection, malignancy, chronic disease), making diagnosis challenging—always check CRP concurrently 1, 4
• Overlooking combined deficiencies: iron deficiency can coexist with B12 or folate deficiency, requiring evaluation if macrocytic indices develop 1, 4
• Failing to distinguish between iron deficiency anemia and anemia of chronic disease, which often overlap—anemia of chronic disease typically shows normal or elevated ferritin with low TSAT 3, 1
• Not investigating the source of iron loss in adults—occult gastrointestinal malignancy must be excluded 1, 4