What labs and medication should be ordered for a patient with microcytic hypochromic anemia (low mean corpuscular volume, low mean corpuscular hemoglobin, elevated red cell distribution width, low serum iron, normal aspartate aminotransferase, elevated erythrocyte sedimentation rate, and peripheral smear showing hypochromasia and microcytosis)?

Laboratory Workup and Treatment for Microcytic Hypochromic Anemia

Order serum ferritin, transferrin saturation (TSAT), and C-reactive protein (CRP) immediately, then initiate oral ferrous sulfate 200 mg three times daily while investigating the source of iron loss through gastrointestinal endoscopy. 1

Immediate Laboratory Tests Required

Essential iron studies:

• Serum ferritin is the single most powerful diagnostic test—your patient's iron of 45 µg/dL is low, but ferritin will confirm absent iron stores if <30 μg/L or <45 μg/L for optimal sensitivity 1, 2
• Transferrin saturation (TSAT) <16-20% confirms iron deficiency even when ferritin appears borderline, and is more sensitive than serum iron alone 1
• C-reactive protein (CRP) to identify inflammation that could falsely elevate ferritin; if CRP is elevated, ferritin up to 100 μg/L may still indicate iron deficiency 1, 2

The combination of MCV 66.2, MCH 20.8, and RDW 16.6% has 91.4% accuracy for iron deficiency anemia rather than thalassemia trait, since thalassemia typically shows RDW ≤14% 1, 2

Additional Testing to Consider

• Hemoglobin electrophoresis should be ordered only if iron studies return normal or borderline, or if the patient belongs to a high-risk ethnic group (Mediterranean, African, Southeast Asian ancestry), as approximately 50% of thalassemia cases can show elevated RDW 1
• Vitamin B12 and folate levels to exclude combined deficiencies, which can coexist with iron deficiency and are suggested by the elevated RDW 1
• Reticulocyte count will be low in iron deficiency, reflecting inadequate bone marrow response 1

Immediate Treatment Protocol

Start oral iron supplementation now while diagnostic workup proceeds:

• Ferrous sulfate 200 mg (65 mg elemental iron) three times daily for at least 3 months after hemoglobin normalizes to replenish iron stores 2
• Add ascorbic acid (vitamin C) with each dose to enhance iron absorption 1, 2
• Alternative formulations (ferrous gluconate or ferrous fumarate) if ferrous sulfate is not tolerated 1

Expected response confirming iron deficiency:

• Hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks 1, 2
• If no response within 2-4 weeks, consider non-compliance, ongoing blood loss (most common), or malabsorption 2

Mandatory Investigation for Source of Iron Loss

The elevated ESR (36 mm/hr) combined with severe microcytic anemia requires urgent investigation for gastrointestinal blood loss, even in the absence of overt bleeding symptoms 1

Required endoscopic evaluation:

• Upper endoscopy with duodenal biopsies to screen for celiac disease (present in 2-3% of iron deficiency cases), gastric malignancy, NSAID gastropathy, and peptic ulcer disease 1, 2
• Colonoscopy to exclude colonic carcinoma, polyps, angiodysplasia, and inflammatory bowel disease 1, 2
• Both procedures are mandatory in adults with confirmed iron deficiency regardless of anemia severity, as gastrointestinal malignancy must be excluded 2

Document NSAID and aspirin use, as these medications cause occult gastrointestinal bleeding 2

Critical Pitfalls to Avoid

• Do not attribute iron deficiency solely to dietary inadequacy—occult gastrointestinal blood loss, especially from malignancy, must be excluded in adults 1
• Do not rely on ferritin alone if inflammation is present (suggested by elevated ESR)—add TSAT to confirm iron deficiency 1
• Do not accept upper GI findings (esophagitis, erosions, ulcers) as the sole cause without also examining the lower GI tract, as dual pathology occurs in 10-15% of patients 1
• Do not assume all microcytic anemia is iron deficiency—anemia of chronic disease (ferritin >100 μg/L with TSAT <20%) and thalassemia require different management 1, 3

If Treatment Fails

Failure to respond within 2-4 weeks warrants:

• Reassess compliance and ongoing blood loss (most common causes) 2
• Switch to intravenous iron (iron sucrose or iron gluconate) if malabsorption is confirmed, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 1, 2
• Consider rare genetic disorders (IRIDA, sideroblastic anemia) if ferritin is low-normal with remarkably low TSAT and failure to respond to both oral and IV iron 1
• Trial of pyridoxine (vitamin B6) 50-200 mg daily if sideroblastic anemia is suspected 1