In an 82‑year‑old woman on levothyroxine and clopidogrel (Plavix) with marked microcytic anemia (RBC 3.12 ×10⁶/µL, hemoglobin 9.3 g/dL, hematocrit 27.1 %, mean corpuscular volume 27.1 fL, red cell distribution width 18.5 %) and no overt bleeding, what is the most likely cause and how should it be evaluated and managed?

Severe Iron Deficiency Anemia Requiring Urgent Investigation

This 82-year-old woman has severe iron deficiency anemia (marked microcytosis with MCV 27.1 fL, elevated RDW 18.5%) that requires immediate gastrointestinal investigation regardless of the absence of overt bleeding, as occult GI blood loss is the most common cause in elderly patients on antiplatelet therapy. 1, 2

Diagnostic Confirmation

The laboratory findings definitively indicate iron deficiency anemia:

• The extremely low MCV of 27.1 fL combined with elevated RDW of 18.5% is pathognomonic for iron deficiency anemia, distinguishing it from thalassemia (which typically has RDW ≤14.0%) 2, 3
• Serum ferritin should be measured immediately, with levels <30 μg/L confirming iron deficiency, though a cut-off of 45 μg/L provides optimal sensitivity and specificity in practice 2, 4
• Transferrin saturation (TSAT) should be added to the workup, as TSAT <16-20% confirms iron deficiency 1, 2
• In elderly patients, ferritin may be falsely elevated by chronic inflammation or malignancy despite true iron deficiency, making TSAT essential for accurate diagnosis 1

Mandatory Investigation for Blood Loss

Fast-track gastrointestinal referral is warranted given hemoglobin 9.3 g/dL in a non-menstruating woman (threshold <100 g/L). 2, 4

Upper GI Endoscopy with Small Bowel Biopsies

• Upper endoscopy reveals a cause in 30-50% of elderly patients with iron deficiency anemia 1
• Small bowel biopsies must be obtained during endoscopy to screen for celiac disease, present in 2-3% of iron deficiency anemia patients 1, 2
• Evaluate for NSAID-induced gastropathy, gastric cancer, angiodysplasia, and peptic ulcer disease 1

Colonoscopy

• Colonoscopy is particularly high-yield in elderly patients for detecting colonic cancer, polyps, and angiodysplasia 1
• The combination of age >80 years and clopidogrel use significantly increases risk of occult GI bleeding 1

Additional Considerations

• Clopidogrel 75 mg daily increases bleeding risk but should NOT deter investigation—the drug should be continued during workup unless active bleeding occurs 1
• Test for H. pylori infection and autoimmune atrophic gastritis as causes of malabsorption 2
• Do not overlook combined deficiencies: iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW 1, 2

Immediate Treatment Algorithm

First-Line Oral Iron Therapy

• Initiate ferrous sulfate 200 mg three times daily immediately, even before completing the diagnostic workup 2, 3, 4
• Alternative formulations (ferrous gluconate or ferrous fumarate) if ferrous sulfate is not tolerated 2, 3
• Adding ascorbic acid (vitamin C) enhances iron absorption 2, 3
• Expected response: hemoglobin rise ≥10 g/L (≥1 g/dL) within 2 weeks confirms iron deficiency 2, 3, 4

Intravenous Iron Indications

• Consider IV iron (iron sucrose or iron gluconate) if malabsorption is documented, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 2, 3
• IV iron may be necessary if oral iron fails due to non-compliance, ongoing blood loss, or true intolerance 2

Duration of Therapy

• Continue oral iron for at least 3 months after hemoglobin correction to replenish iron stores 2, 3, 4

Monitoring Protocol

• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then again at 2 years 2, 3, 4
• Provide additional oral iron if hemoglobin or MCV falls below normal 2, 3, 4
• Recheck ferritin and TSAT after 3 months of therapy to confirm iron store repletion 2

Critical Pitfalls to Avoid

• Never assume dietary insufficiency alone explains severe iron deficiency in an elderly patient—GI investigation is mandatory 1, 2
• Do not stop clopidogrel for investigation unless active bleeding occurs—the cardiovascular risk of discontinuation typically outweighs bleeding risk during endoscopy 1
• Failure to respond to oral iron within 2-4 weeks should prompt consideration of malabsorption, ongoing blood loss, non-compliance, or rare genetic disorders (IRIDA) 2, 3
• Hypothyroidism (patient on levothyroxine) can contribute to anemia but does not explain this degree of microcytosis—iron deficiency must be the primary focus 5, 6

Special Consideration: Levothyroxine

• While hypothyroidism can cause normocytic or mild microcytic anemia, the extreme microcytosis (MCV 27.1 fL) cannot be attributed to thyroid dysfunction alone 5, 6
• Ensure levothyroxine dose is optimized, as thyroid hormones stimulate erythropoiesis, but this is secondary to treating iron deficiency 5