What is the appropriate work‑up and management for a 49‑year‑old woman with iron‑deficiency anemia (hemoglobin 9.9 g/dL, microcytosis, low serum iron, low ferritin, high total iron‑binding capacity)?

Iron Deficiency Anemia: Work-Up and Management

This 49-year-old woman has clear-cut iron deficiency anemia requiring immediate investigation for gastrointestinal blood loss and prompt iron replacement therapy. 1

Confirming the Diagnosis

Your patient's laboratory values unequivocally establish iron deficiency anemia:

• Hemoglobin 9.9 g/dL meets WHO criteria for anemia in non-pregnant women (< 12 g/dL) and warrants full investigation regardless of severity. 1
• Ferritin 8.3 µg/L is highly specific (99% specificity) for absolute iron deficiency, well below the diagnostic threshold of < 15 µg/L. 1
• Transferrin saturation 5% (calculated as serum iron 22 ÷ UIBC 402 × 100) is markedly below the < 20% cutoff that confirms iron deficiency. 1
• MCV 72 fL and MCH 18.7 pg demonstrate microcytosis and hypochromia, the hallmark red-cell changes of iron deficiency. 1
• RDW 20.9% (elevated above 14%) indicates marked variation in red-cell size, an early and sensitive marker of iron deficiency. 1, 2

No additional iron studies are needed—this constellation is diagnostic. 1

Mandatory Investigation for Blood Loss

In a 49-year-old woman, iron deficiency anemia is presumed to be caused by gastrointestinal blood loss until proven otherwise, and occult malignancy must be excluded. 1, 3

Immediate Steps

• Order fecal occult blood testing to screen for gastrointestinal bleeding. 3
• Refer for bidirectional endoscopy (upper endoscopy and colonoscopy) because colorectal and gastric cancers are the most common serious causes in this age group. 1
• Do not delay endoscopy even though hemoglobin is above the fast-track referral threshold (< 10 g/dL for non-menstruating women), because investigation should be considered at any level of anemia in the presence of iron deficiency. 1

Additional Considerations

• Assess menstrual history carefully. Although menstruation is a common cause of iron deficiency in premenopausal women, at age 49 perimenopausal bleeding patterns may be irregular, and gastrointestinal pathology must still be ruled out. 4
• Screen for celiac disease with tissue transglutaminase antibodies (IgA) and total IgA, because celiac disease impairs duodenal iron absorption and is frequently missed. 2
• Test for Helicobacter pylori via stool antigen or urea breath test, as chronic infection can cause iron malabsorption and gastric atrophy. 2

Iron Replacement Therapy

Start oral iron supplementation immediately while the diagnostic work-up proceeds. 1, 4

Dosing and Formulation

• Prescribe elemental iron 100–200 mg daily (e.g., ferrous sulfate 325 mg three times daily provides 195 mg elemental iron). 4
• Advise taking iron on an empty stomach to maximize absorption, but if gastrointestinal side effects are intolerable, taking it with food is acceptable. 4
• Continue therapy for at least 3–6 months after hemoglobin normalizes to fully replenish iron stores (target ferritin > 50 µg/L). 1, 4

Monitoring Response

• Recheck complete blood count and reticulocyte count in 2–4 weeks. A rising reticulocyte count within 1 week and hemoglobin increase of ≥ 1 g/dL by 4 weeks confirms adequate response. 4
• If hemoglobin fails to rise after 4 weeks of oral iron, consider non-compliance, ongoing blood loss, malabsorption (celiac disease, atrophic gastritis, H. pylori), or iron-refractory iron deficiency anemia (IRIDA) due to TMPRSS6 mutations. 2, 5
• Intravenous iron is indicated if oral iron is not tolerated, malabsorption is documented, or hemoglobin fails to improve despite adherence. 1

Excluding Alternative Causes of Microcytosis

Although your patient's iron studies are diagnostic, hemoglobin electrophoresis should be ordered if microcytosis persists after iron repletion or if the patient has an appropriate ethnic background (Mediterranean, African, Middle Eastern, Southeast Asian) to exclude beta-thalassemia trait. 1, 3

• Beta-thalassemia trait typically shows MCV reduced out of proportion to the degree of anemia (MCV often < 70 fL with hemoglobin 10–12 g/dL), elevated hemoglobin A2 > 3.5%, and normal or elevated ferritin. 1, 3
• Anemia of chronic disease is excluded by your patient's very low ferritin; anemia of chronic disease shows ferritin > 100 µg/L, low total iron-binding capacity, and transferrin saturation < 20%. 1, 3

Common Pitfalls to Avoid

• Do not assume menstruation alone explains severe iron deficiency in a perimenopausal woman. Gastrointestinal pathology must be investigated. 1
• Do not stop iron therapy once hemoglobin normalizes. Iron stores must be replenished (ferritin > 50 µg/L) to prevent rapid recurrence. 1, 4
• Do not attribute microcytosis to thalassemia trait without first confirming and treating iron deficiency. Iron deficiency and thalassemia can coexist, and iron deficiency must be corrected before hemoglobin electrophoresis can be accurately interpreted. 1, 2
• Do not delay endoscopy waiting for iron therapy to work. Investigation for malignancy should proceed in parallel with treatment. 1