What is the diagnosis and treatment plan for a patient with microcytic hypochromic anemia and potential iron deficiency anemia, as indicated by low hemoglobin, hematocrit, MCV, MCH, and MCHC levels on CBC results?

Microcytic Hypochromic Anemia: Diagnosis and Management

Immediate Diagnostic Workup

This patient has clear iron deficiency anemia requiring immediate iron studies (serum ferritin and transferrin saturation) to confirm the diagnosis and guide treatment. 1

The CBC pattern is diagnostic:

• Persistently low hemoglobin (11.9-12.8 g/dL) with progressive microcytosis (MCV declining from 74.3 to 71.1 fL) and hypochromia (MCH 21.2-22.4 pg, MCHC 28.9-30.9 g/dL) strongly indicates iron deficiency anemia. 1
• The normal RDW (13.0-13.6%) is atypical but does not exclude iron deficiency—a low MCV with RDW >14.0% suggests iron deficiency while RDW ≤14.0% suggests thalassemia trait, though this is not absolute. 1
• MCH is more reliable than MCV as a marker of iron deficiency because it's less dependent on storage conditions and is reduced in both absolute and functional iron deficiency. 1

Essential Laboratory Tests

Order immediately:

• Serum ferritin: levels <30 μg/L confirm iron deficiency, though a cut-off of 45 μg/L provides optimal sensitivity and specificity in practice. 1
• Transferrin saturation (TSAT): <16-20% supports iron deficiency and is more sensitive than hemoglobin alone. 1, 2
• C-reactive protein: if elevated, ferritin up to 100 μg/L may still indicate iron deficiency. 1
• Reticulocyte count: to evaluate bone marrow response. 2

If ferritin is normal or elevated despite microcytosis, add hemoglobin electrophoresis to exclude thalassemia trait, particularly given the extreme microcytosis (MCV <72 fL). 1

Treatment Algorithm

First-Line Therapy

Start oral iron supplementation with ferrous sulfate 324 mg (65 mg elemental iron) three times daily immediately, even before iron studies return, given the clear microcytic hypochromic pattern. 1, 3

• Add ascorbic acid (vitamin C) to enhance iron absorption. 1
• Continue treatment for at least three months after hemoglobin normalizes to replenish iron stores. 1
• Alternative formulations (ferrous gluconate or ferrous fumarate) can be used if ferrous sulfate is not tolerated. 1

Expected Response and Monitoring

A good response is defined as hemoglobin rise ≥10 g/L (≥1 g/dL) within 2 weeks, which confirms iron deficiency. 1

• Monitor hemoglobin and red cell indices at 2 weeks, then at three-monthly intervals for one year, then after a further year. 1, 4
• If hemoglobin fails to rise by at least 2 g/dL within 4 weeks, consider non-compliance, ongoing blood loss, malabsorption, or rare genetic disorders. 1

Management of Treatment Failure

If no response to oral iron after 2-4 weeks:

1. Consider intravenous iron (iron sucrose or iron gluconate) if malabsorption is present, with expected hemoglobin increase of at least 2 g/dL within 4 weeks. 1
2. Evaluate for genetic disorders of iron metabolism, particularly IRIDA (iron-refractory iron deficiency anemia) if there is remarkably low TSAT with low-to-normal ferritin and failure to respond to oral iron. 1
3. Consider pyridoxine (vitamin B6) 50-200 mg daily if X-linked sideroblastic anemia (ALAS2 defects) is suspected, continuing lifelong at 10-100 mg daily if responsive. 1

Investigation of Underlying Cause

All adults with confirmed iron deficiency require investigation for the source of iron loss—this is mandatory, not optional. 1

High-Priority Investigations

• Men with hemoglobin <110 g/L or non-menstruating women with hemoglobin <100 g/L warrant fast-track gastrointestinal referral with endoscopy. 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 (occult bleeding, melena, hematochezia) 1
• Menstrual blood loss in premenopausal women 1
• Malabsorption disorders: celiac disease, H. pylori infection, autoimmune atrophic gastritis 1
• Dietary inadequacy 1

Screen for celiac disease if malabsorption is suspected. 1

Critical Pitfalls to Avoid

Do Not Miss Combined Deficiencies

Iron deficiency can coexist with B12 or folate deficiency—evaluate for macrocytic indices and vitamin levels if there is inadequate response to iron alone. 1, 4

Do Not Assume All Microcytic Anemia is Iron Deficiency

Anemia of chronic disease, thalassemia, and sideroblastic anemia must be differentiated to avoid unnecessary or harmful iron therapy. 1

• If microcytosis persists with normal iron studies, order hemoglobin electrophoresis, especially in patients of Mediterranean, African, Middle Eastern, or Southeast Asian descent. 1
• 7% of patients have both thalassemia trait and iron deficiency—check ferritin even when thalassemia is diagnosed. 4

Do Not Use Ferritin Alone in Inflammatory States

Ferritin can be falsely elevated by inflammation, chronic disease, malignancy, or liver disease—add TSAT to the diagnostic workup. 1, 2

• In the presence of inflammation, ferritin up to 100 μg/L may still indicate iron deficiency. 1
• TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease, not iron deficiency. 1

Special Genetic Considerations

If there is extreme microcytosis (MCV <70 fL), family history of refractory anemia, or failure to respond to both oral and intravenous iron, consider genetic testing for disorders like SLC11A2, STEAP3, SLC25A38, ALAS2, or TMPRSS6 (IRIDA). 1

• For IRIDA, intravenous iron is required as oral iron is typically ineffective. 1
• For SLC25A38 defects, hematopoietic stem cell transplantation is the only curative option, with symptomatic treatment including transfusions and chelation. 1