What is the appropriate management plan for a patient with mild anemia and elevated Red Cell Distribution Width (RDW)?

Management of Mild Anemia with Elevated RDW

This patient requires serum ferritin testing to confirm iron deficiency, followed by both upper endoscopy with small bowel biopsy and colonoscopy to exclude gastrointestinal malignancy, as the elevated RDW (16.4%) strongly suggests iron deficiency anemia. 1

Laboratory Interpretation

The patient presents with:

• Mild anemia (Hemoglobin 11.8 g/dL, just below the lower limit of normal) 2
• Elevated RDW (16.4%, reference range 11.5-15.0%), which is the critical finding 1
• Low-normal MCV (81.5 fL) with borderline low MCH (26.2 pg) 2
• Low hematocrit (36.7%) 2

The elevated RDW indicates a heterogeneous red cell population, which is characteristic of iron deficiency anemia rather than thalassemia trait or anemia of chronic disease 1, 3. Iron deficiency typically presents with RDW >14.0% due to the presence of both older normocytic cells and newer microcytic cells 1. In contrast, thalassemia trait typically shows low or normal RDW with homogeneous microcytic cells 1, 4.

Essential Diagnostic Workup

Immediate Laboratory Tests Required

• Serum ferritin (<30 μg/L suggests iron deficiency; <12 μg/L is diagnostic) 2, 1
• Transferrin saturation (<30% supports iron deficiency) 1
• C-reactive protein (CRP) to assess for inflammation that might elevate ferritin 1
• Peripheral blood smear to assess red cell morphology 1

Note that ferritin may be falsely elevated above 12-15 μg/dL in patients with concurrent chronic inflammation, malignancy, or hepatic disease, though if >100 μg/dL, iron deficiency is almost certainly not present 2.

Critical Pitfall to Avoid

Do not empirically treat with iron supplementation before confirming iron deficiency with ferritin testing. 1 While the elevated RDW strongly suggests iron deficiency, you must document this biochemically before initiating treatment, as empirical iron therapy in thalassemia patients can cause iron overload 1.

Gastrointestinal Investigation Protocol

Once iron deficiency is confirmed, all adult men and post-menopausal women require complete gastrointestinal evaluation regardless of symptom severity. 2, 1

Mandatory Endoscopic Evaluation

• Upper gastrointestinal endoscopy with small bowel biopsy to exclude gastric cancer, celiac disease, and other upper GI pathology 2
• Colonoscopy or barium enema to exclude colonic malignancy and polyps 2

The rationale is compelling: gastrointestinal blood loss is the most common cause of iron deficiency in men and post-menopausal women, and asymptomatic gastric and colonic carcinomas frequently present with iron deficiency anemia 2. Even mild anemia warrants full investigation, as severity does not correlate with the likelihood of serious underlying disease 2, 1.

Common GI Sources to Consider

• Occult blood loss: NSAID use, colonic cancer/polyps, angiodysplasia 2
• Malabsorption: Celiac disease (most frequent), gastrectomy, bacterial overgrowth 2
• Gastric pathology: Gastric cancer, gastric atrophy 2
• Inflammatory conditions: Crohn's disease, ulcerative colitis 2

Treatment Algorithm

If Iron Deficiency is Confirmed

1. Initiate iron supplementation (oral ferrous sulfate 325 mg daily or intravenous if intolerant/malabsorption) 1
2. Complete endoscopic evaluation as outlined above 2, 1
3. Treat underlying cause identified on investigation 2
4. Recheck CBC and ferritin in 8 weeks to assess response 3

If Ferritin is Normal/Elevated

• Consider combined deficiencies (iron plus folate or B12), which can result in normal MCV despite iron deficiency and may be recognized by elevated RDW 2, 1
• Check vitamin B12 and folate levels 5
• Assess for anemia of chronic disease with inflammatory markers 1
• Consider hemoglobin electrophoresis if thalassemia is suspected based on ethnicity, though less likely given the elevated RDW 1, 6

Special Considerations for Pre-menopausal Women

If this patient is a pre-menopausal woman, menstrual blood loss is the most common cause 2. However, gastrointestinal investigation should still be pursued if:

• Ferritin is very low (<12 μg/L) 2
• Anemia is refractory to iron supplementation 2
• There are any gastrointestinal symptoms 2

Monitoring and Follow-up

After initiating iron therapy, expect to see:

• RDW improvement with progressive normalization over 8 weeks 3
• Hemoglobin rise of approximately 1-2 g/dL over 3-4 weeks 3
• Red cell morphology normalization on peripheral smear 3

Treatment of the underlying cause will cure the anemia, and even when no cause is detected, the long-term outlook is good 2.