What diagnosis and work‑up are indicated for a patient with chronic mild microcytic, hypochromic anemia (hemoglobin ~12 g/dL, red blood cell count high‑normal, mean corpuscular volume ~72 fL, mean corpuscular hemoglobin ~22 pg, mean corpuscular hemoglobin concentration ~30 g/dL, red cell distribution width normal‑high) and otherwise normal white blood cell count, platelet count, and mean platelet volume?

Chronic Microcytic Hypochromic Anemia: Diagnosis and Work-Up

This patient requires immediate serum ferritin and transferrin saturation testing to confirm iron deficiency anemia, followed by investigation for gastrointestinal blood loss as the most likely underlying cause. 1

Initial Diagnostic Testing

The laboratory pattern—MCV ~72 fL, MCH ~22 pg, MCHC ~30 g/dL, and hemoglobin ~12 g/dL—is characteristic of iron deficiency anemia. 2 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

First-Line Laboratory Tests

• Serum ferritin is the single most powerful test for confirming iron deficiency, with levels <15 μg/L indicating absent iron stores and <30 μg/L indicating low body iron stores. 1
• A ferritin cut-off of 45 μg/L provides optimal sensitivity and specificity for iron deficiency in clinical practice. 2, 1
• Transferrin saturation should be added if ferritin appears falsely normal due to inflammation, with TSAT <16-20% confirming iron deficiency. 1
• The normal-high RDW (13.2-13.6%) combined with low MCV suggests iron deficiency rather than thalassemia trait, which typically presents with normal RDW. 1

Critical Distinction: When to Consider Alternative Diagnoses

If ferritin is >100 μg/L, iron deficiency is almost certainly not present, and alternative diagnoses must be pursued. 1 However, in the presence of inflammation, ferritin up to 100 μg/L may still be consistent with iron deficiency. 1

Hemoglobin Electrophoresis Indications

Order hemoglobin electrophoresis if:

• Microcytosis persists with normal iron studies 1
• MCV is disproportionately low relative to the degree of anemia 1
• Patient has appropriate ethnic background (Mediterranean, African, Southeast Asian descent) 1
• RDW is normal or near-normal despite microcytosis 1

Beta-thalassemia trait typically shows elevated hemoglobin A2 levels (>3.5%) and more extreme microcytosis (MCV often <70 fL) with minimal anemia. 3

Investigation for Underlying Cause

All adults with confirmed iron deficiency anemia require investigation for the source of iron loss, as dietary insufficiency alone rarely causes iron deficiency in developed countries. 1

Gastrointestinal Evaluation

Men with hemoglobin <110 g/L or non-menstruating women with hemoglobin <100 g/L should be referred for fast-track gastrointestinal evaluation. 2, 1 However, investigation should be considered at any level of anemia with confirmed iron deficiency, especially with more severe degrees. 2

Required endoscopic procedures:

• Upper endoscopy with duodenal biopsies to exclude celiac disease (present in 2-3% of iron deficiency anemia patients), gastric malignancy, NSAID-induced gastropathy, peptic ulcer disease, and angiodysplasia 1
• Colonoscopy to exclude colonic carcinoma, polyps, angiodysplasia, and inflammatory bowel disease 1

Additional Investigations

• Detailed menstrual history in premenopausal women, as heavy menstrual bleeding is the most common cause in this population 1
• Medication review for NSAIDs, antiplatelet agents (aspirin, clopidogrel), or anticoagulants that increase bleeding risk 1
• Dietary assessment for inadequate iron intake, though this alone rarely causes iron deficiency in adults 1
• Screen for celiac disease if malabsorption is suspected 2

Rare Genetic Considerations

If iron studies show remarkably low TSAT with low-to-normal ferritin AND the patient fails to respond to oral iron therapy, consider rare genetic disorders: 1

• IRIDA (iron-refractory iron deficiency anemia): Autosomal recessive TMPRSS6 mutations causing resistance to oral iron but potential response to intravenous iron 1
• X-linked sideroblastic anemia (ALAS2 defects): May respond to pyridoxine (vitamin B6) 50-200 mg daily initially, then 10-100 mg daily lifelong if responsive 1, 4
• Other genetic disorders (SLC11A2, STEAP3, SLC25A38): Consider if extreme microcytosis (MCV <70 fL), family history of refractory anemia, or elevated ferritin with microcytosis 1, 4

Bone marrow examination looking for ring sideroblasts is recommended if ferritin is normal/high with abnormal iron studies, as this is definitive for sideroblastic anemia. 4

Treatment Initiation

Begin oral iron supplementation immediately while diagnostic work-up proceeds. 1 The recommended regimen is ferrous sulfate 200 mg three times daily for at least three months after correction of anemia to replenish iron stores. 2

Expected Response

A good response to iron therapy is defined as hemoglobin rise ≥10 g/L within 2 weeks, which confirms iron deficiency. 2, 1 If the patient fails to respond within 2-4 weeks, consider non-compliance, ongoing blood loss, malabsorption, or rare genetic disorders. 1

Critical Pitfalls to Avoid

• Do not attribute iron deficiency anemia in adults solely to dietary insufficiency—occult gastrointestinal blood loss, especially from malignancy, must be excluded. 1
• Do not assume all microcytic anemia is iron deficiency—anemia of chronic disease (TSAT <20% with ferritin >100 μg/L), thalassemia, and sideroblastic anemia require different management. 1
• Do not rely on ferritin alone when inflammation is present—add transferrin saturation to the diagnostic workup. 1
• Do not overlook combined deficiencies—iron deficiency can coexist with vitamin B12 or folate deficiency, suggested by elevated RDW. 1
• Do not delay gastrointestinal investigation even when heavy menstrual bleeding appears explanatory in women. 1

Monitoring Protocol

Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year, then after a further year. 2 Check serum ferritin and transferrin saturation to assess iron store repletion, and provide additional oral iron if hemoglobin or MCV falls below normal. 2