What is the appropriate diagnosis and treatment plan for a patient with severe iron deficiency (ferritin 4 ng/mL, transferrin 393 mg/dL, total iron‑binding capacity 491 µg/dL), mild anemia (hemoglobin 10.9 g/dL, hematocrit 34.1 %), borderline low vitamin B12 (148 pg/mL) and normal folate?

Diagnosis: Combined Iron Deficiency Anemia and Borderline Vitamin B12 Deficiency

This patient has severe iron deficiency anemia (IDA) with a ferritin of 4 ng/mL, and borderline low vitamin B12 at 148 pg/mL that likely represents functional deficiency secondary to the iron deficiency rather than true B12 deficiency. 1

Diagnostic Interpretation

Iron Status Analysis

• Ferritin 4 ng/mL is diagnostic of absolute iron deficiency, as values <12-15 μg/L confirm depleted iron stores regardless of inflammation status 2
• The transferrin saturation can be calculated: TSAT = (serum iron × 100) ÷ TIBC. With TIBC of 491 μg/dL, even if serum iron were 50 μg/dL, TSAT would be approximately 10%, well below the 16-20% threshold, confirming inadequate iron delivery to bone marrow 2, 3
• The elevated TIBC (491 μg/dL, normal 250-370) and transferrin (393 mg/dL, normal 200-400) indicate the body's compensatory response to severe iron depletion 2
• This is pure iron deficiency anemia, not anemia of chronic disease, since ferritin is far below 30 μg/L 2, 3

Vitamin B12 Interpretation

• The borderline low B12 (148 pg/mL) in the context of severe IDA likely represents a pseudodeficiency that will normalize with iron repletion 1
• Research demonstrates that serum vitamin B12 and folate levels increase significantly during treatment of IDA with pharmacological iron, with all patients having baseline B12 ≤200 pmol/L rising above 200 pmol/L after iron therapy 1
• Do not initiate B12 supplementation immediately; instead, recheck B12 levels after 8-10 weeks of iron therapy 2, 1

Anemia Severity

• Hemoglobin 10.9 g/dL represents moderate anemia (WHO defines anemia as <12 g/dL in women, <13 g/dL in men) 2
• The chloride of 108 mEq/L is at the upper limit of normal but not clinically significant in this context

Treatment Plan

Immediate Iron Replacement

Initiate oral iron supplementation at 100-200 mg elemental iron daily in divided doses 2

• Alternate-day dosing (100-200 mg every other day) may provide better absorption with fewer gastrointestinal side effects 2
• Common side effects include constipation, diarrhea, and nausea; counsel the patient accordingly 2

When to Use Intravenous Iron

Consider IV iron if:

• The patient fails to achieve a 1-2 g/dL hemoglobin increase after 4 weeks of oral therapy 4
• Severe gastrointestinal intolerance prevents oral iron adherence 2
• Rapid repletion is needed (though not typically urgent at hemoglobin 10.9 g/dL) 2

If IV iron is required, use ferric carboxymaltose 1000 mg infused over 15 minutes, which allows rapid single-dose administration 2

Mandatory Gastrointestinal Evaluation

All patients with confirmed IDA require GI investigation to identify the source of blood loss, unless there is documented significant non-GI blood loss 2

Perform upper endoscopy with small bowel biopsies to evaluate for:

• Celiac disease (present in 2-3% of IDA patients) 2
• Gastric cancer, peptic ulcer disease, or angiodysplasia 2
• Take duodenal biopsies even without visible lesions 2

Perform colonoscopy to evaluate for:

• Colon cancer or polyps (particularly in patients >50 years) 2
• Inflammatory bowel disease 2
• Angiodysplasia 2

Dual pathology occurs in approximately 10% of cases, so complete both upper and lower GI evaluation even if one study reveals a lesion 2

Monitoring and Follow-Up

Recheck complete blood count and iron studies at 4 weeks:

• Expect hemoglobin increase of 1-2 g/dL if treatment is effective 4
• If hemoglobin fails to increase appropriately, consider malabsorption, ongoing blood loss, or unidentified lesion 4

Recheck vitamin B12 at 8-10 weeks after initiating iron therapy:

• B12 should normalize without supplementation if the low value was secondary to iron deficiency 1
• If B12 remains <200 pg/mL after iron repletion, then initiate B12 supplementation 1

Do not recheck ferritin immediately after IV iron, as levels will be falsely elevated; wait 8-10 weeks 2

Critical Pitfalls to Avoid

• Do not attribute the anemia solely to B12 deficiency and miss the severe iron deficiency, which is the primary driver of anemia here 1
• Do not delay GI evaluation assuming dietary insufficiency is the cause; even with poor diet, full investigation is mandatory 2
• Do not stop aspirin or NSAIDs if the patient is taking them, but document their use as they are common causes of occult GI blood loss 2
• Do not assume normal ferritin excludes iron deficiency in inflammatory states (not applicable here, but important principle) 2, 3
• Do not give blood transfusion at hemoglobin 10.9 g/dL unless the patient is symptomatic or hemodynamically unstable 2