What is the most likely cause and treatment for a patient with microcytic anemia, low Mean Corpuscular Volume (MCV), and elevated Red Cell Distribution Width (RDW)?

Microcytic Anemia with Elevated RDW: Iron Deficiency Until Proven Otherwise

The combination of low MCV and elevated RDW is pathognomonic for iron deficiency anemia and mandates immediate serum ferritin testing followed by comprehensive gastrointestinal evaluation in adult men and post-menopausal women to exclude malignancy. 1

Why This Pattern Matters

The elevated RDW is the critical distinguishing feature that separates iron deficiency from other microcytic anemias:

• High RDW (>14-16.9%) strongly distinguishes iron deficiency from thalassemia trait, which typically presents with normal or only slightly elevated RDW 1
• The elevated RDW reflects heterogeneous red cell populations as iron stores become progressively depleted, creating a distinctive signature 1
• Combined deficiency (e.g., iron plus folate or B12) may present with elevated RDW even when MCV appears normal, making RDW elevation particularly valuable 2

Immediate Diagnostic Algorithm

Step 1: Confirm Iron Deficiency

Serum ferritin is the single most powerful test and must be obtained immediately 2, 1:

• Ferritin <12 μg/dL is diagnostic of iron deficiency 2
• Ferritin <30 μg/L confirms iron deficiency in the absence of inflammation 1
• Ferritin <100 μg/L may still indicate iron deficiency if concurrent inflammation, malignancy, or hepatic disease is present 2, 1
• Ferritin >100 μg/dL makes iron deficiency almost certainly absent 2

Step 2: Assess for Inflammation

Measure simultaneously with ferritin 1:

• Transferrin saturation <30% supports iron deficiency 2, 1
• C-reactive protein (CRP) to interpret ferritin correctly in the context of inflammation 1

Mandatory Gastrointestinal Investigation

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

Upper GI Evaluation

• Upper endoscopy with mandatory small bowel biopsies to exclude malignancy and detect coeliac disease (present in 2-3% of IDA patients) 2, 1
• Upper GI endoscopy reveals a cause in 30-50% of patients 2

Lower GI Evaluation

• Colonoscopy or CT colonography to exclude colonic cancer/polyps 1
• In elderly patients, investigation of the colon is likely to be more productive 2

Common GI Sources to Consider 2:

• NSAID use (most common cause of occult GI blood loss)
• Colonic cancer/polyps
• Gastric cancer
• Angiodysplasia
• Coeliac disease (requires small bowel biopsy confirmation)
• Crohn's disease, ulcerative colitis

Critical pitfall: Never assume dietary insufficiency or NSAID use as the sole cause without completing full GI evaluation, as these may coexist with malignancy 2

Treatment Protocol

Once Iron Deficiency is Confirmed (Ferritin <30 μg/L)

Initiate oral iron supplementation immediately 1:

• Continue for 3-6 months after hemoglobin normalizes to replete iron stores 1
• The vast majority of patients respond effectively to inexpensive oral iron preparations 3
• Parenteral iron dextran is reserved for malabsorption, losses exceeding maximal oral replacement, or true intolerance 3

Addressing the Underlying Cause

Treatment of the underlying cause will cure the anemia 1:

• Stop NSAIDs and anticoagulants whenever possible 2
• Address any identified GI pathology 1
• Document menstrual history in pre-menopausal women 2

Critical Diagnostic Pitfalls to Avoid

Do Not Confuse with Thalassemia

• Thalassemia trait presents with low MCV but normal or low RDW, not elevated RDW 4, 1
• Thalassemia typically shows elevated red cell count despite microcytosis 2
• Never attribute microcytosis to thalassemia in certain ethnic groups without laboratory confirmation via hemoglobin electrophoresis 4

Do Not Miss Combined Deficiencies

• Combined iron and folate/B12 deficiency may present with normal MCV despite iron deficiency, but elevated RDW will be present 2, 4
• This pattern requires checking both iron studies and folate/B12 levels 4

Do Not Overlook Anemia of Chronic Disease

• Anemia of chronic disease may present with microcytosis but typically has low-normal RDW 2
• Distinguished by low iron levels with decreased total iron-binding capacity 5
• Iron supplementation is generally ineffective as the body cannot utilize stored iron 4

Special Populations Requiring Heightened Vigilance

Even mild anemia warrants investigation, as severity does not correlate with likelihood of serious underlying disease 4:

• Adult men: GI blood loss is the most common cause 2
• Post-menopausal women: Presumed GI blood loss until proven otherwise 2, 1
• Pregnant patients: Require special considerations to prevent significant morbidity and mortality 6
• Patients with heart failure: Iron deficiency requires special management considerations 6