In an asymptomatic adult with normal white‑blood‑cell count, normal red‑blood‑cell count, hemoglobin 12.9 g/dL, hematocrit 43 %, low mean corpuscular hemoglobin (25.5 pg) and low mean corpuscular hemoglobin concentration (29.9 g/dL), elevated red‑cell distribution width (RDW‑CV 18.7 %), high mean platelet volume (12.7 fL), and otherwise normal differential, what is the most appropriate next step in management?

Management of Low MCH and MCHC with Elevated RDW in an Asymptomatic Adult

Order a complete iron panel immediately (serum ferritin, transferrin saturation, serum iron, and C-reactive protein) to confirm iron deficiency anemia, which is the most likely diagnosis given the combination of low MCH (25.5 pg), low MCHC (29.9 g/dL), and markedly elevated RDW-CV (18.7%). 1, 2

Why This Pattern Strongly Suggests Iron Deficiency

• Low MCH and MCHC indicate hypochromic anemia, meaning red blood cells contain less hemoglobin than normal, which most commonly results from iron deficiency 1, 2
• MCH is a more reliable marker of iron deficiency than MCV because it is less dependent on storage conditions and laboratory equipment, and it decreases in both absolute and functional iron deficiency 1
• The markedly elevated RDW-CV (18.7%) is highly characteristic of iron deficiency anemia, reflecting increased variation in red cell size (anisocytosis) that occurs as iron-deficient cells are produced alongside older normal cells 3, 4
• RDW above 17.1 strongly suggests iron deficiency anemia and helps distinguish it from other causes of microcytic anemia such as thalassemia trait, which typically has RDW <17.1 4
• The normal RBC count (5.06) with low hemoglobin indices represents compensatory erythropoiesis, where the bone marrow produces more red cells to compensate for reduced oxygen-carrying capacity, a pattern typical of iron deficiency 1

Interpreting the Iron Studies

If Ferritin is Low (Confirms Iron Deficiency)

• Ferritin <15 μg/L confirms absent iron stores; ferritin <30 μg/L indicates low body iron stores in patients without inflammation 1, 2
• Transferrin saturation <16-20% supports iron deficiency and is less affected by inflammation than ferritin 1, 2

If Ferritin is Borderline or Normal (Consider Inflammation)

• Check C-reactive protein (CRP) to assess for inflammation, which can falsely elevate ferritin as an acute-phase reactant 1, 2
• In patients with inflammation, ferritin up to 100 μg/L may still indicate iron deficiency, so use higher diagnostic thresholds 1, 2
• Ferritin >150 μg/L makes absolute iron deficiency unlikely even with inflammation 1
• If ferritin is 30-100 μg/L with elevated CRP, consider combined iron deficiency and anemia of chronic disease 1

If Iron Studies Confirm Iron Deficiency: Investigate the Cause

In an asymptomatic adult, iron deficiency always requires investigation for the underlying source of blood loss or malabsorption. 2

Mandatory Gastrointestinal Evaluation

• Upper endoscopy and colonoscopy are mandatory to exclude gastrointestinal malignancy, which is the most common cause in adult men and post-menopausal women 2
• Small bowel biopsy during endoscopy should be performed to rule out celiac disease 2
• Screen for NSAID use, which can cause occult GI bleeding 2

Additional Investigations

• In pre-menopausal women, assess menstrual blood loss as a potential cause 2
• Evaluate for malabsorption, particularly if there are any gastrointestinal symptoms 2
• Consider chronic kidney disease screening, as CKD is associated with anemia 2

Treatment: Oral Iron Supplementation

Initiate oral iron supplementation with ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals as first-line therapy once iron deficiency is confirmed 1

Expected Response and Monitoring

• Expect hemoglobin increase of approximately 1-2 g/dL every 2-4 weeks with appropriate treatment 1, 2
• Reticulocyte count should increase within 1 week of starting therapy, indicating bone marrow response 1
• Repeat CBC and iron studies after 4-8 weeks to confirm response 1, 2
• Continue iron supplementation for 3-6 months after hemoglobin normalizes to replenish iron stores 1, 2

When to Consider Intravenous Iron

• Consider parenteral iron if the patient is intolerant to oral iron, has poor response to oral iron, has malabsorption, or requires rapid correction 1, 2

If Iron Studies Are Normal: Consider Alternative Diagnoses

Thalassemia Trait

• Order hemoglobin electrophoresis, especially in individuals of Mediterranean, African, or Southeast Asian descent 1, 2
• Thalassemia trait produces microcytosis with low MCH but normal iron parameters, and MCV is typically reduced disproportionately to the degree of anemia 1

Other Considerations

• Anemia of chronic disease can present with low MCHC and normal or mildly elevated ferritin 2
• Sideroblastic anemia is a rare cause that should be considered if other diagnoses are excluded 1, 2

Additional Findings in This Case

Elevated Mean Platelet Volume (MPV 12.7 fL)

• Elevated MPV is commonly seen with iron deficiency anemia as a reactive phenomenon, though it is non-specific 5

Normal White Blood Cell Parameters

• The normal WBC count and differential exclude primary hematologic malignancies as the cause of the anemia 5

Critical Pitfalls to Avoid

• Do not rely on MCV alone, as iron deficiency can present with normal MCV in early stages, and MCH may be more sensitive 1
• Do not dismiss normal ferritin in inflammatory states; use higher cutoffs (45-100 μg/L) depending on inflammation severity 1, 2
• Do not forget to investigate the cause of iron deficiency, as it often indicates ongoing blood loss requiring evaluation, including potential malignancy 2
• Do not treat empirically without confirming the diagnosis with iron studies first 1
• Do not assume the patient is asymptomatic without specifically asking about fatigue, exercise intolerance, and other subtle symptoms of iron deficiency 6