What does a low hemoglobin, low hematocrit, low mean corpuscular volume (MCV) and low mean corpuscular hemoglobin (MCH) indicate?

Microcytic Hypochromic Anemia (Iron Deficiency Pattern)

Low hemoglobin, low hematocrit, low MCV, and low MCH together indicate microcytic hypochromic anemia, most commonly caused by iron deficiency anemia. 1

What This Pattern Means

• Microcytic anemia (MCV < 80 fL) combined with low MCH (hypochromia) creates a highly specific pattern for iron-deficient erythropoiesis, where red blood cells are both smaller and contain less hemoglobin than normal 1, 2

• The bone marrow produces progressively smaller red blood cells with less hemoglobin content as iron stores become depleted, resulting in the characteristic low MCV and low MCH pattern 1

• MCH is actually more reliable than MCV for detecting iron deficiency because it's less dependent on storage conditions and laboratory equipment, and it decreases in both absolute and functional iron deficiency 1, 2

Most Common Cause: Iron Deficiency Anemia

• Iron deficiency is the most common cause of this pattern, accounting for the majority of microcytic hypochromic anemias in clinical practice 1, 3, 4

• In one study of healthy blood donors with low MCV, 64% had iron deficiency (49% isolated iron deficiency, 15% iron deficiency plus hemoglobinopathy) 4

Diagnostic Workup Required

Essential initial tests to confirm iron deficiency: 1, 2

• Serum ferritin - the single most useful marker:

  • < 15 μg/L confirms absent iron stores 2
  • < 30 μg/L confirms low body iron stores 1, 2
  • 45 μg/L cut-off provides optimal sensitivity and specificity in routine practice 2

• Transferrin saturation (TSAT) - especially important if inflammation is present:

  • < 15-16% strongly supports iron deficiency 1, 2
  • TSAT < 20% with ferritin > 100 μg/L suggests anemia of chronic disease instead 2

• Red cell distribution width (RDW) - helps differentiate causes:

  • Elevated RDW (> 14%) with low MCV strongly suggests iron deficiency 2
  • Normal RDW with low MCV suggests thalassemia trait 2

• Reticulocyte count - evaluates bone marrow response 1

• C-reactive protein - to assess for inflammation that may falsely elevate ferritin 2

Critical Pitfall: Ferritin Can Be Falsely Elevated

• Ferritin is an acute phase reactant and can be falsely elevated by inflammation, chronic disease, malignancy, or liver disease 1, 2

• In the presence of inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 2

• When inflammation is present, add transferrin saturation to confirm the diagnosis - TSAT < 16-20% confirms iron deficiency even with elevated ferritin 2

Other Causes to Consider (Less Common)

If iron studies are normal, consider: 1, 2

• Thalassemia trait - especially if:

  • MCV disproportionately low relative to degree of anemia 2
  • RDW normal or near-normal (≤ 14%) 2
  • Appropriate ethnic background (Mediterranean, Asian, African descent) 2
  • Order hemoglobin electrophoresis to confirm 1, 2

• Anemia of chronic disease - if TSAT < 20% with ferritin > 100 μg/L and inflammatory markers present 2

• Sideroblastic anemia - rare genetic disorder affecting heme synthesis 2, 3

Mandatory Investigation for Underlying Cause

Once iron deficiency is confirmed, you must investigate the source of iron loss: 2

• Adult men and postmenopausal women require gastrointestinal evaluation (upper endoscopy and colonoscopy) to exclude malignancy 1, 2

• Premenopausal women require evaluation of both menstrual losses AND gastrointestinal sources 2

• Upper endoscopy with duodenal biopsies screens for celiac disease (present in 2-3% of iron deficiency cases) 2

• Colonoscopy evaluates for colon cancer, polyps, and angiodysplasia 2

• Consider malabsorption disorders (celiac disease, H. pylori, atrophic gastritis) if treatment fails 2

Treatment Approach

• First-line treatment is oral iron (ferrous sulfate 200 mg three times daily) for at least 3 months after anemia correction to replenish stores 2

• Expected response: hemoglobin should rise ≥ 10 g/L (≥ 1 g/dL) within 2 weeks if iron deficiency is the cause 2

• If no response to oral iron within 2-4 weeks, consider non-compliance, ongoing blood loss, malabsorption, or rare genetic disorders 2

• Intravenous iron is indicated for malabsorption, intolerance to oral iron, or need for rapid repletion, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 1, 2

Key Clinical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency - anemia of chronic disease, thalassemia, and sideroblastic anemia require different management 1, 2

• Do not rely on ferritin alone in inflammatory states - it can be falsely elevated; add transferrin saturation 2

• Do not overlook combined deficiencies - iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW 2

• Do not attribute iron deficiency in adults to diet alone - occult gastrointestinal blood loss, especially from malignancy, must be excluded 2

• Do not delay gastrointestinal investigation in adults with confirmed iron deficiency, even when another explanation (like heavy menses) seems obvious 2