What does it mean if a patient has low Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC) levels on a complete blood count?

Low MCV, MCH, and MCHC: Microcytic Hypochromic Anemia

Low MCV, MCH, and MCHC together indicate microcytic hypochromic anemia, most commonly caused by iron deficiency anemia, which should be confirmed with serum ferritin and transferrin saturation before initiating treatment. 1

What This Pattern Means

• Microcytic anemia (MCV < 80 fL) combined with low MCH and low MCHC indicates red blood cells that are both smaller than normal and contain less hemoglobin than normal 1, 2
• This specific pattern reflects defective hemoglobin synthesis in developing red blood cells, causing the bone marrow to produce progressively smaller, paler cells 1
• MCH is actually more reliable than MCHC for detecting iron deficiency because it is less dependent on storage conditions and laboratory equipment 1

Most Common Causes (In Order of Frequency)

Iron Deficiency Anemia (Most Common)

• Iron deficiency is the leading cause of microcytic anemia in adults and should be your first consideration 2, 3
• The progression occurs in stages: anisocytosis (increased RDW) appears first, then MCV and MCH decline, and finally MCHC drops in severe deficiency 4
• If iron studies exclude iron deficiency, then consider thalassemia trait as the next most likely diagnosis 3

Thalassemia Trait (Second Most Common)

• Thalassemia minor typically presents with microcytosis but can be distinguished from iron deficiency by a normal or only slightly elevated RDW (≤14.0%), whereas iron deficiency usually shows RDW >14.0% 5, 6
• Patients with thalassemia trait often have a particularly low MCV (often <70 fL) despite minimal or no anemia 2

Other Causes to Consider

• Anemia of chronic disease/inflammation can cause microcytosis, though typically less severe than iron deficiency 5, 3
• Lead toxicity should be considered in appropriate clinical contexts 5, 3
• Sideroblastic anemia is a rare inherited cause that can present with microcytosis 2

Essential Diagnostic Workup

First-Line Tests (Order These Immediately)

• Serum ferritin is the single most useful marker: levels <30 μg/L confirm iron deficiency in the absence of inflammation 1, 6
• Transferrin saturation <15-16% supports iron deficiency and is less affected by inflammation than ferritin 1, 6
• Red cell distribution width (RDW): elevated (>14.0%) suggests iron deficiency; normal or minimally elevated suggests thalassemia 5, 6
• Reticulocyte count to evaluate bone marrow response 1, 6

Critical Interpretation Pitfalls

• Ferritin can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease, potentially masking iron deficiency 1, 6
• In the presence of inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 6
• Consider measuring C-reactive protein (CRP) to identify concurrent inflammation that affects ferritin interpretation 6

Second-Line Tests (If Iron Studies Are Normal)

• Hemoglobin electrophoresis to detect thalassemia trait, particularly in patients of Mediterranean, African, Middle Eastern, or Southeast Asian descent 3
• Patients with beta-thalassemia trait typically show elevated hemoglobin A2 levels 3

Clinical Action Based on Results

If Iron Deficiency Is Confirmed

• Investigate the underlying cause of iron deficiency—it does not occur in isolation 1, 6
• In adult men and postmenopausal women, presume gastrointestinal blood loss until proven otherwise, including evaluation for malignancy 6, 3
• In premenopausal women, consider menstrual losses but do not automatically attribute iron deficiency to menses without investigation 1
• Treat with oral iron supplementation as first-line, or intravenous iron if oral is not tolerated, poorly absorbed, or rapid repletion is needed 1

If Iron Studies Are Normal

• Proceed with hemoglobin electrophoresis to evaluate for thalassemia trait 3
• Consider anemia of chronic disease and assess for underlying inflammatory conditions 1, 3
• Evaluate for lead exposure in appropriate clinical contexts 5, 3

Key Distinguishing Features

Feature	Iron Deficiency	Thalassemia Trait
RDW	Usually >14.0% [5,6]	Normal or ≤14.0% [5]
Ferritin	<30 μg/L [1,6]	Normal [3]
Transferrin Saturation	<15-16% [1]	Normal [3]
MCV severity	Variable [1]	Often <70 fL [2]
Hemoglobin A2	Normal [3]	Elevated in beta-thal [3]