What is the appropriate diagnosis and management for a patient with anemia characterized by low MCHC (Mean Corpuscular Hemoglobin Concentration) and elevated RDW (Red Cell Distribution Width)?

Diagnosis and Management of Low MCHC with Elevated RDW

The combination of low MCHC and elevated RDW is highly suggestive of iron deficiency anemia, and you should immediately confirm this with serum ferritin testing (<30 μg/L confirms iron deficiency in the absence of inflammation), then investigate for gastrointestinal blood loss as the underlying cause. 1, 2

Understanding This Specific Pattern

• Elevated RDW reflects heterogeneous red cell populations with varying sizes as iron stores become depleted, making it a specific indicator of iron deficiency 1
• Low MCHC indicates reduced hemoglobin concentration within red cells, which is characteristic of iron deficiency but can also occur in thalassemia (though thalassemia typically has normal or elevated red cell counts) 3
• This combination (low MCHC + high RDW) strongly favors iron deficiency over thalassemia, as thalassemia typically presents with low MCV and RDW ≤14.0%, while iron deficiency shows RDW >14.0% 2

Immediate Diagnostic Workup

First-Line Testing

• Serum ferritin is the single most powerful test for iron deficiency: <15 μg/L indicates absent iron stores, <30 μg/L indicates low body iron stores 1, 2
• Transferrin saturation <30% supports iron deficiency diagnosis and provides insight into circulating iron available for red cell production 3, 1
• C-reactive protein (CRP) is essential to interpret ferritin correctly, as inflammation elevates ferritin and can mask true iron deficiency 1

Critical Interpretation Points

• If ferritin is 30-100 μg/L with elevated CRP, iron deficiency may still be present despite the "normal" ferritin due to concurrent inflammation 1, 2
• Ferritin >100 μg/L makes iron deficiency almost certainly absent, even with inflammation 3
• Ferritin >150 μg/L essentially excludes absolute iron deficiency even with concurrent inflammation 2

Investigation for Underlying Cause

Mandatory GI Evaluation

• All adult men and post-menopausal women with confirmed iron deficiency require gastrointestinal evaluation regardless of hemoglobin level or presence of symptoms 1, 2
• Upper endoscopy with small bowel biopsies should be performed first: 30-50% will have an upper GI source identified, and 2-3% have celiac disease 3, 1, 2
• Colonoscopy or CT colonography is mandatory even if upper GI source is found, as dual pathology occurs in approximately 10% of patients 1

Key History Elements

• Document NSAID and aspirin use (common cause of occult GI blood loss), and stop these medications whenever possible 3
• Dietary history should be obtained but never presumed as the sole cause—full GI investigation is still required even with borderline deficient diet 3
• Family history of thalassemia or hemoglobinopathies should be sought, particularly in patients of Mediterranean, African, or Southeast Asian descent 3

Treatment Approach

• Initiate oral iron supplementation once iron deficiency is confirmed by ferritin testing (or intravenous if malabsorption or intolerance present) 1
• Continue iron for 3-6 months after hemoglobin normalizes to fully replete iron stores 1
• Therapeutic response to 3 weeks of oral iron confirms the diagnosis when other tests are equivocal 3, 2

Critical Pitfalls to Avoid

• Never assume dietary insufficiency alone without completing GI evaluation—this can miss serious underlying pathology including malignancy 3, 1
• Do not start empiric iron therapy without confirming iron deficiency, as this can cause harm in thalassemia patients and delays proper diagnosis 1
• Ferritin is an acute phase reactant—it can be falsely normal or elevated during inflammation, infection, malignancy, or liver disease despite true iron deficiency 2
• Combined deficiencies (iron plus B12/folate) can mask typical findings—elevated RDW may be the only clue when MCV appears normal due to competing deficiencies 3, 2

When to Consider Alternative Diagnoses

• If iron studies are normal with persistent low MCHC and microcytosis, obtain hemoglobin electrophoresis to evaluate for thalassemia trait 2
• Thalassemia typically shows MCV reduced out of proportion to anemia level, with RDW ≤14.0% and normal or elevated red cell count 2
• Anemia of chronic disease may present similarly but typically has ferritin >100 μg/L and low transferrin saturation 3