What is the appropriate treatment for iron‑deficiency anemia with low mean corpuscular volume, low mean corpuscular hemoglobin, and high red‑cell distribution width?

Treatment for Iron Deficiency Anemia with Low MCV, Low MCH, and High RDW

Initiate oral iron supplementation immediately once iron deficiency is confirmed with serum ferritin testing, as the combination of low MCV, low MCH, and elevated RDW is pathognomonic for iron deficiency anemia. 1, 2

Confirm the Diagnosis First

Before starting treatment, you must confirm iron deficiency with laboratory testing:

• Obtain serum ferritin immediately—this is the single most powerful diagnostic test 1, 2
• Ferritin <30 μg/L confirms iron deficiency in the absence of inflammation 3, 1, 2
• Ferritin <12 μg/L is diagnostic regardless of inflammatory status 1, 2
• If inflammation is present (check CRP), ferritin up to 100 μg/L may still indicate iron deficiency 3, 1, 2
• Transferrin saturation <30% provides additional confirmation 3, 1, 2

The high RDW (>14%) with low MCV/MCH strongly distinguishes iron deficiency from thalassemia trait, which typically presents with normal or only slightly elevated RDW 3, 1, 2. This elevated RDW reflects heterogeneous red cell populations as iron stores become progressively depleted 1.

Oral Iron Therapy (First-Line Treatment)

Start oral iron supplementation as soon as iron deficiency is confirmed: 1, 2

• Continue treatment for 3-6 months after hemoglobin normalizes to fully replete iron stores 1
• Recent evidence suggests intermittent dosing (e.g., every other day) is as effective as daily dosing with fewer gastrointestinal side effects 4
• If diagnostic uncertainty remains, response to three weeks of oral iron can confirm true iron deficiency 2

Intravenous Iron (Second-Line)

Switch to intravenous iron if the patient: 4

• Cannot tolerate oral iron due to gastrointestinal side effects
• Cannot absorb oral iron (e.g., inflammatory bowel disease, celiac disease)
• Does not respond to adequate oral iron therapy

For IV iron (ferric carboxymaltose): 5

• Patients ≥50 kg: 750 mg IV in two doses separated by at least 7 days (total 1,500 mg per course)
• Patients <50 kg: 15 mg/kg body weight IV in two doses separated by at least 7 days
• Alternative single-dose option for adults: 15 mg/kg up to maximum 1,000 mg IV as single dose

Mandatory Investigation for Underlying Cause

All adult men and post-menopausal women with confirmed iron deficiency require complete gastrointestinal evaluation, regardless of symptom presence or anemia severity: 1, 2

• Upper endoscopy with mandatory small bowel biopsies to exclude malignancy and detect celiac disease (present in 2-3% of IDA patients) 1
• Colonoscopy or CT colonography to exclude colorectal cancer and polyps 1
• Do not skip this investigation—occult malignancy must be excluded, and even mild anemia warrants full evaluation 1, 2

Common GI sources to investigate include: 1, 2

• NSAID use (stop whenever possible)
• Colorectal cancer/polyps
• Gastric cancer
• Angiodysplasia
• Celiac disease
• Inflammatory bowel disease (Crohn's, ulcerative colitis)

Critical Pitfalls to Avoid

• Do not assume thalassemia based on ethnicity alone—the high RDW strongly argues against thalassemia trait and favors iron deficiency 2
• Do not skip GI investigation in adult men and post-menopausal women—GI blood loss is the most common cause in these populations, not dietary deficiency 2
• Do not overlook combined deficiencies—iron deficiency can coexist with folate or B12 deficiency, which may normalize MCV but maintain elevated RDW 1, 2
• Stop NSAIDs and aspirin whenever possible as these are common culprits for ongoing blood loss 1, 2
• Document anticoagulant use but do not let this deter investigation—these patients still require full GI evaluation 2

Monitoring Response

• Recheck hemoglobin and ferritin after completing the initial treatment course 1
• If IDA recurs, repeat treatment may be necessary 5
• For repeat IV iron courses within 3 months, check serum phosphate levels as hypophosphatemia can occur 5