How should I interpret a mild normocytic‑to‑slightly‑hypochromic anemia with hemoglobin (Hb) 12 g/dL, hematocrit (Hct) 38.8 %, mean corpuscular volume (MCV) 86.8 fL, mean corpuscular hemoglobin (MCH) 26.8 pg, mean corpuscular hemoglobin concentration (MCHC) 30.9 g/dL, and what are the recommended next steps?

Interpretation and Management of Mild Normocytic-to-Slightly-Hypochromic Anemia

This presentation with Hb 12.0 g/dL, low MCH (26.8 pg), and low MCHC (30.9 g/dL) indicates evolving iron deficiency anemia, and you must immediately check serum ferritin and transferrin saturation to confirm the diagnosis before initiating iron supplementation. 1

Understanding the Laboratory Pattern

The combination of low MCH and low MCHC is more specific for iron deficiency than MCV alone, because MCH is less dependent on storage conditions and decreases in both absolute and functional iron deficiency. 2 Your patient's MCV remains normal (86.8 fL) while MCH and MCHC are already reduced, representing early-stage iron deficiency where hemoglobin synthesis is impaired before red cell size becomes overtly microcytic. 1, 2

Key Diagnostic Features:

• MCH 26.8 pg (low) combined with MCHC 30.9 g/dL (low) strongly suggests hypochromic anemia, most commonly from iron deficiency 2
• The normal MCV does not exclude iron deficiency—MCH is actually more sensitive for detecting early iron depletion 2
• Serial values show progressive decline in hemoglobin (14.8 → 13.6 → 14.2 → 12.0 g/dL), confirming this is not laboratory error 1

Immediate Diagnostic Workup

Order the following tests immediately to establish the cause:

Essential Iron Studies:

• Serum ferritin: The single most powerful test for iron deficiency 1, 2

  • <15 μg/L = absent iron stores 1
  • <30 μg/L = low body iron stores (confirms iron deficiency in non-inflammatory states) 1, 2
  • 30-100 μg/L = possible combined iron deficiency and anemia of chronic disease 2

  • 100 μg/L = makes pure iron deficiency unlikely unless inflammation present 3, 2

• Transferrin saturation (TSAT): Measures circulating iron available for erythropoiesis 2

  • <16-20% = insufficient iron for red cell production 1, 2
  • This is more reliable than ferritin when inflammation is present 3

• C-reactive protein (CRP): Essential to interpret ferritin correctly 3, 1

  • If CRP elevated, ferritin up to 100 μg/L may still indicate iron deficiency 3, 2

Additional Helpful Tests:

• Red cell distribution width (RDW): Low MCV with RDW >14.0% suggests iron deficiency, while RDW ≤14.0% suggests thalassemia trait 1, 2
• Reticulocyte count: Assesses bone marrow response; should be elevated if bleeding is the cause 3
• Complete blood count review: Check white blood cells and platelets—abnormalities in multiple cell lines warrant hematology consultation 3

Critical Pitfall to Avoid

Do not assume this is "just borderline normal" or attribute it to laboratory variation. The progressive decline in hemoglobin combined with hypochromic indices (low MCH/MCHC) indicates active ongoing iron loss or deficiency that will worsen without intervention. 1, 2

Ferritin is an acute-phase reactant and can be falsely normal or elevated during inflammation, infection, malignancy, or liver disease despite true iron deficiency. 2 If ferritin appears "normal" (30-150 μg/L) but TSAT is low (<20%), you likely have either functional iron deficiency or combined iron deficiency with inflammation. 3, 2

Investigating the Underlying Cause

Once iron deficiency is confirmed, you must identify the source of iron loss—do not simply treat empirically without investigation in adults. 1

In Adult Women (Premenopausal):

• Heavy menstrual bleeding is the most common cause 1
• However, gastrointestinal blood loss must still be excluded unless menstrual loss fully accounts for the severity 1
• Consider gynecologic evaluation for menorrhagia 1

In Adult Men or Postmenopausal Women:

• Gastrointestinal blood loss is the most common cause and mandates endoscopic evaluation 1, 2
• Upper endoscopy with duodenal biopsies (to screen for celiac disease, present in 2-3% of iron deficiency cases) 1, 2
• Colonoscopy to exclude colonic carcinoma, polyps, angiodysplasia, or inflammatory bowel disease 1

Other Causes to Consider:

• Malabsorption disorders: Celiac disease, H. pylori infection, autoimmune atrophic gastritis 1
• Dietary inadequacy: Less common in developed countries but assess nutritional intake 1
• Medications: NSAIDs, antiplatelet agents (aspirin, clopidogrel) increase GI bleeding risk 1

Treatment Algorithm

Step 1: Confirm Iron Deficiency

• If ferritin <30 μg/L (or <100 μg/L with inflammation) AND TSAT <20%: Diagnose iron deficiency anemia 2

Step 2: Initiate Iron Supplementation

Start oral iron immediately while diagnostic workup proceeds: 1

• Ferrous sulfate 200 mg three times daily (or equivalent elemental iron 150-200 mg/day) 1
• Alternative formulations if not tolerated: ferrous gluconate or ferrous fumarate 1
• New evidence supports intermittent dosing (every other day) with fewer side effects and similar efficacy 4
• Adding ascorbic acid (vitamin C) enhances absorption 1

Step 3: Assess Response

• Hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks if iron deficiency is the cause 1, 2
• Recheck CBC at 2-4 weeks to confirm response 1
• Continue iron for at least 3 months after correction to replenish stores 1

Step 4: If No Response to Oral Iron

Consider: 1

• Non-compliance (most common)
• Ongoing blood loss exceeding replacement
• Malabsorption (celiac disease, H. pylori, atrophic gastritis)
• Intravenous iron if malabsorption confirmed (expect Hb increase ≥2 g/dL within 4 weeks) 1, 2
• Rare genetic disorders: IRIDA (iron-refractory iron deficiency anemia) if remarkably low TSAT with low-normal ferritin and failure to respond to both oral and IV iron 1

Alternative Diagnoses to Consider

If Iron Studies Are Normal:

• Anemia of chronic disease: Ferritin >100 μg/L with TSAT <20% 2
• Thalassemia trait: Normal iron studies with microcytosis, low MCV disproportionate to anemia, RDW normal or low, appropriate ethnic background (Mediterranean, Southeast Asian, African) 1, 2
  • Order hemoglobin electrophoresis if suspected 1
• Combined deficiencies: Iron deficiency can coexist with B12 or folate deficiency (elevated RDW is a clue) 1, 2

If Ferritin 30-100 μg/L:

• Combined iron deficiency and anemia of chronic disease is likely 3, 2
• Treat the underlying inflammatory condition and provide iron supplementation 2

Monitoring and Follow-Up

• Recheck CBC, ferritin, and TSAT at 3-month intervals for the first year after correction 1
• Provide additional oral iron if hemoglobin or MCV falls below normal 1
• Investigate recurrence aggressively—recurrent iron deficiency in adults always requires explanation 1, 2

Common Pitfalls Summary

1. Do not overlook combined deficiencies: Iron deficiency may coexist with B12 or folate deficiency (elevated RDW is the clue) 1, 2
2. Do not rely on ferritin alone in inflammatory states: Add TSAT to confirm iron deficiency 2
3. Do not assume all microcytic anemia is iron deficiency: Anemia of chronic disease, thalassemia, and sideroblastic anemia require different management 1, 2
4. Do not attribute iron deficiency in adults to diet alone: Occult GI blood loss, especially malignancy, must be excluded 1
5. Do not delay GI investigation in adults with confirmed iron deficiency, even when another explanation (e.g., menorrhagia) seems obvious 1