In a 67-year-old man with low mean corpuscular hemoglobin (MCH) and low mean corpuscular hemoglobin concentration (MCHC), what is the most likely diagnosis and recommended treatment?

Diagnosis and Treatment of Low MCH and MCHC in a 67-Year-Old Male

Most Likely Diagnosis

The most likely diagnosis is iron-deficiency anemia, which is the most common cause of low MCH (26.0 pg) and low MCHC (31.3 g/dL), both indicating hypochromic red blood cells with insufficient hemoglobin content. 1, 2

Immediate Diagnostic Workup

Order a comprehensive iron panel immediately to confirm the diagnosis and guide treatment, including: 1, 3

• Serum ferritin – the single most specific test for iron deficiency; <15 μg/L confirms absent iron stores, <30 μg/L indicates low body iron stores 1, 2
• Transferrin saturation (TSAT) – values <16-20% support iron deficiency and are less affected by inflammation than ferritin 1, 3
• C-reactive protein (CRP) – to assess for inflammation, which can falsely elevate ferritin 1, 3
• Complete blood count with MCV and RDW – to determine if anemia is microcytic and assess red cell size variation 1, 3
• Reticulocyte count – to evaluate bone marrow response; low/normal values indicate impaired red cell production 1, 3

Interpreting Iron Studies

Without Inflammation (Normal CRP)

• Ferritin <30 μg/L confirms iron deficiency and warrants immediate treatment 1, 2
• TSAT <16-20% supports the diagnosis 1, 2

With Inflammation (Elevated CRP)

• Ferritin up to 100 μg/L may still indicate iron deficiency because ferritin is an acute-phase reactant 1, 2
• Ferritin >150 μg/L makes absolute iron deficiency unlikely even with inflammation 1
• Use TSAT <16-20% as the primary indicator when inflammation is present 2

Treatment for Confirmed Iron Deficiency

Initiate oral iron supplementation as first-line therapy: 1

• Ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals 1
• Expect hemoglobin increase of approximately 1-2 g/dL every 2-4 weeks 1
• Continue iron for 3-6 months after hemoglobin normalizes to replenish iron stores 1
• Recheck hemoglobin, reticulocytes, and iron studies after 4-8 weeks of therapy 1

When to Use Intravenous Iron

Consider parenteral iron if: 1, 4

• Patient is intolerant to oral iron
• Poor response to oral iron after 4-8 weeks
• Severe anemia requiring rapid correction
• Malabsorption is present

Investigating the Underlying Cause

In a 67-year-old male, iron deficiency almost always indicates ongoing blood loss requiring evaluation: 1, 2

• Gastrointestinal bleeding is the most common cause in adult men and postmenopausal women 1, 2
• Order stool guaiac testing for occult blood 3
• Refer for upper endoscopy with duodenal biopsies and colonoscopy to exclude malignancy, angiodysplasia, or celiac disease (2-3% of iron-deficiency cases) 2

Alternative Diagnoses if Iron Studies Are Normal

If ferritin and TSAT are normal despite low MCH/MCHC, consider: 1, 3

Thalassemia Trait

• Order hemoglobin electrophoresis, especially in patients of Mediterranean, African, or Southeast Asian descent 1, 3
• Thalassemia typically shows: MCV disproportionately reduced relative to anemia, microcytosis with low MCH, normal iron parameters, and RDW ≤14% 1, 2

Anemia of Chronic Disease

• Diagnosed when ferritin >100 μg/L and TSAT <20% 2
• Treat the underlying inflammatory condition rather than iron supplementation 3, 2

Sideroblastic Anemia

• Consider if iron studies show elevated ferritin with low MCHC 2
• Requires bone marrow examination for definitive diagnosis 3

Critical Pitfalls to Avoid

• Do not rely on MCV alone – iron deficiency can present with normal MCV in early stages, and MCH is more sensitive 1, 3
• Do not dismiss normal ferritin in inflammatory states – use the higher cutoff of 45-100 μg/L depending on inflammation severity 1, 2
• Do not forget to investigate the cause – iron deficiency in a 67-year-old male mandates GI evaluation for malignancy 1, 2
• Do not interpret ferritin without concurrent CRP – inflammation raises ferritin independently of iron stores 3, 2

Confirming the Diagnosis Through Treatment Response

A rise in hemoglobin of ≥10 g/L (≈1 g/dL) within 2 weeks of iron therapy strongly confirms absolute iron deficiency, even if baseline iron studies were equivocal 1, 3