Causes of Low MCV, MCH, and MCHC
Low MCV, MCH, and MCHC together indicate microcytic hypochromic anemia, most commonly caused by iron deficiency anemia, followed by thalassemia trait, anemia of chronic disease, and rarely lead poisoning. 1, 2
Primary Differential Diagnosis
The combination of low MCV, MCH, and MCHC narrows the differential significantly:
Iron Deficiency Anemia (Most Common)
- Iron deficiency is the most common cause of microcytic anemia worldwide and typically presents with all three indices reduced 1, 3
- Characterized by low MCV with elevated Red Cell Distribution Width (RDW >14.0%), which helps distinguish it from other causes 4, 1
- Serum ferritin <15 μg/L definitively confirms iron deficiency 1, 2
- In the presence of inflammation, ferritin up to 45-100 μg/L may still indicate iron deficiency 1, 2
- Ferritin >100 μg/L essentially rules out iron deficiency even with inflammation 1, 2
- Progressive stages exist: anisocytosis and microcytosis occur first, then MCV and MCH decline, and finally MCHC drops in severe deficiency 5
Thalassemia Trait (Second Most Common)
- Low MCV with normal RDW (≤14.0%) strongly suggests thalassemia minor rather than iron deficiency 1, 2
- Microcytosis is often more pronounced relative to the degree of anemia compared to iron deficiency 2
- Serum ferritin and iron studies are normal or elevated, unlike iron deficiency 2
- Hemoglobin electrophoresis is required for definitive diagnosis 4, 1
- Critical pitfall: Inappropriate iron therapy in thalassemia can cause iron overload 2
Anemia of Chronic Disease
- Can present with microcytosis, particularly when prolonged, though MCV rarely falls below 70 fL 4, 2
- Diagnostic criteria in the presence of inflammation: serum ferritin >100 μg/L and transferrin saturation <20% 4
- If ferritin is between 30-100 μg/L, a combination of true iron deficiency and anemia of chronic disease is likely 4
- Inflammatory cytokines upregulate hepcidin production, creating functional iron deficiency for erythropoiesis 4
Lead Poisoning
- Rare cause of microcytic anemia in modern practice 4, 2
- Should be considered in patients with appropriate exposure history 4
Diagnostic Algorithm
Step 1: Confirm microcytosis and obtain RDW
- MCV <80 fL in adults confirms microcytic anemia 1, 3
- RDW >14.0% suggests iron deficiency 4, 1
- RDW ≤14.0% suggests thalassemia trait 1, 2
Step 2: Measure serum ferritin as the single most powerful test
- Ferritin <15 μg/L = definitive iron deficiency 1, 2
- Ferritin 15-45 μg/L without inflammation = probable iron deficiency 1
- Ferritin 30-100 μg/L with inflammation = possible iron deficiency or mixed picture 4, 1
- Ferritin >100 μg/L = iron deficiency ruled out; consider anemia of chronic disease 4, 1
Step 3: If RDW is normal and ferritin is normal/elevated
- Obtain hemoglobin electrophoresis to diagnose thalassemia 4, 1
- Elevated red blood cell count with low MCV further supports thalassemia 4
Step 4: For confirmed iron deficiency in adult men and post-menopausal women
- Gastrointestinal investigation is mandatory unless significant non-gastrointestinal blood loss is evident 1
- Upper gastrointestinal endoscopy with small bowel biopsies reveals a cause in 30-50% of patients and detects coeliac disease in 2-3% 1
- Colonoscopy or barium enema should be performed to exclude gastrointestinal malignancy 1
Critical Clinical Pitfalls
- Do not assume all microcytic anemias are iron deficiency—low RDW with low MCV strongly suggests thalassemia, and inappropriate iron therapy causes iron overload 1, 2
- Normal MCV, MCH, and MCHC do not exclude iron deficiency in early stages or combined deficiency states 2, 6
- In patients with both iron deficiency and thalassemia, Hb, MCV, MCH, and MCHC values are significantly lower than either condition alone 7
- Microcytosis from iron deficiency in cyanotic heart disease patients increases risk of cerebrovascular events, particularly when caused by inappropriate phlebotomies 4
- False elevation of MCHC can occur due to cold agglutination or lipemia, requiring correction before interpretation 8