What is the next step in managing a patient with normal hemoglobin (Hgb) levels, high Red Cell Distribution Width (RDW), and low Mean Corpuscular Hemoglobin (MCH)?

Management of Normal Hemoglobin with High RDW and Low MCH

Check serum ferritin, transferrin saturation, and CRP immediately to identify early or evolving iron deficiency, as high RDW with low MCH strongly suggests iron deficiency even when hemoglobin remains normal. 1

Understanding the Clinical Pattern

This combination of findings represents a critical diagnostic pattern that warrants immediate investigation:

• High RDW is a specific indicator of iron deficiency, reflecting heterogeneous red cell populations with varying sizes as iron stores become depleted 1
• Low MCH indicates reduced hemoglobin content per red cell, which occurs early in iron deficiency before frank anemia develops 1, 2
• Normal hemoglobin does not exclude iron deficiency—it may represent early-stage deficiency or compensated iron depletion 3, 4

The high RDW distinguishes this from thalassemia trait (which typically shows low/normal RDW with homogeneous microcytic cells) and makes iron deficiency the primary concern 1, 3

Essential Diagnostic Workup

Minimum Required Tests

Obtain these laboratory studies immediately:

• Serum ferritin: <30 μg/L confirms iron deficiency in the absence of inflammation; <100 μg/L suggests iron deficiency when inflammation is present 1
• Transferrin saturation: <30% supports iron deficiency diagnosis 1, 3
• C-reactive protein (CRP): Essential to interpret ferritin levels correctly, as inflammation elevates ferritin and can mask true iron deficiency 1, 3
• Complete reticulocyte count: Low or normal reticulocytes indicate inappropriate erythropoiesis from deficiency; elevated reticulocytes suggest hemolysis or active bleeding 1

Additional Testing if Initial Workup is Equivocal

• Vitamin B12 and folate levels: Combined deficiencies can normalize MCV despite iron deficiency, though RDW remains elevated 1, 3
• Hemoglobin electrophoresis: Only if thalassemia is suspected based on ethnicity, but low RDW would be expected in thalassemia, not high 1, 3

Investigation for Underlying Causes

If Iron Deficiency is Confirmed

All adult men and post-menopausal women with confirmed iron deficiency require gastrointestinal evaluation regardless of hemoglobin level or symptom presence 1, 3:

• Upper endoscopy with small bowel biopsies: 30-50% will have an upper GI source; 2-3% have celiac disease 1
• Colonoscopy or CT colonography: Dual pathology occurs in ~10% of patients, so lower GI evaluation is mandatory even if upper GI source is found (unless gastric or esophageal cancer is identified) 1
• Document NSAID/aspirin use: Stop these medications when possible, but their use should not defer investigation 1

Pre-menopausal Women

• Menstrual blood loss is the most common cause, but do not assume this is the sole etiology 1
• Consider GI evaluation if: heavy menstrual bleeding is absent, iron supplementation fails, or any GI symptoms are present 1

Treatment Approach

If Iron Deficiency is Documented

• Initiate oral iron supplementation (or intravenous if malabsorption or intolerance) once iron deficiency is confirmed by ferritin testing 3
• Do not give empiric iron without confirming deficiency—this risks iron overload if thalassemia trait is the actual diagnosis 3
• Continue iron for 3-6 months after hemoglobin normalizes to replete stores 1

If Iron Studies are Normal

• Reassess for combined deficiencies (B12, folate) that may cause elevated RDW 1
• Consider hemolysis workup: Check haptoglobin, LDH, and bilirubin if reticulocytes are elevated 1
• Evaluate for chronic disease: Inflammatory conditions can cause similar patterns 1

Critical Pitfalls to Avoid

• Never assume normal hemoglobin excludes significant pathology—mild anemia or pre-anemic iron deficiency can indicate serious underlying disease including malignancy 1, 3
• Do not attribute findings to dietary insufficiency alone—even with poor diet, full GI investigation is required in at-risk populations 1
• Avoid empiric iron therapy without confirming iron deficiency, as this can cause harm in thalassemia patients and delays proper diagnosis 3
• Do not skip lower GI evaluation if upper endoscopy finds a lesion (except for malignancy)—dual pathology is common 1