Low MCV and Low MCH: Diagnostic Interpretation
Low MCV (mean corpuscular volume) and low MCH (mean corpuscular hemoglobin) indicate microcytic hypochromic anemia, most commonly caused by iron deficiency anemia, though thalassemia and anemia of chronic disease must also be considered. 1, 2
Primary Differential Diagnosis
The combination of low MCV and low MCH represents microcytic hypochromic red blood cells, which narrows the differential to three main categories:
- Iron deficiency anemia is the most common cause of microcytic anemia worldwide and should be your first consideration 2, 3
- Thalassemia minor (trait) presents with microcytosis often more pronounced relative to the degree of anemia 2
- Anemia of chronic inflammation/infection can cause microcytosis, especially when prolonged 2
Algorithmic Diagnostic Approach
Step 1: Check Red Cell Distribution Width (RDW)
The RDW is critical for differentiating between causes:
- High RDW (>14.0%) + Low MCV/MCH strongly suggests iron deficiency anemia 2, 4
- Normal RDW (≤14.0%) + Low MCV/MCH strongly suggests thalassemia minor 2, 4
Step 2: Obtain Iron Studies
Serum ferritin is the single most useful marker for iron deficiency 1:
- Ferritin <15 μg/L is highly specific (99%) for iron deficiency 1
- Ferritin <30 μg/L generally indicates low body iron stores 1
- Ferritin <45 μg/L may warrant investigation, especially with chronic inflammation (specificity 92%) 1, 2
- Ferritin >100-150 μg/L essentially rules out iron deficiency even with inflammation 1, 2
Step 3: Consider Additional Testing Based on Iron Studies
If iron studies are normal or elevated with low MCV/MCH:
- Obtain hemoglobin electrophoresis to evaluate for thalassemia, particularly in patients of Mediterranean, African, Middle Eastern, or Southeast Asian descent 1
- Serum ferritin and iron studies are normal or elevated in beta thalassemia, unlike in iron deficiency 2
If iron deficiency is confirmed:
- Investigate the underlying cause, particularly gastrointestinal blood loss in adult men and post-menopausal women 2
- Consider upper endoscopy with small bowel biopsy and colonoscopy to exclude gastrointestinal malignancy in the absence of overt blood loss 2
Important Clinical Nuances
MCH may be more sensitive than MCV for detecting iron deficiency:
- MCH is less dependent on storage conditions and counting machines 1
- MCH reduction occurs in both absolute and functional iron deficiency 1
- In research settings, MCH demonstrated slightly better diagnostic accuracy than MCV (AUC 0.73-0.96 vs 0.68-0.93) 5
Ferritin interpretation requires clinical context:
- Ferritin is an acute phase protein and can be falsely normal in inflammatory conditions 1
- In the presence of inflammation, consider iron deficiency even with ferritin up to 45 μg/L 1, 2
Critical Pitfalls to Avoid
- Don't assume all microcytic anemias are iron deficiency - low RDW with low MCV strongly suggests thalassemia minor, and unnecessary iron therapy in thalassemia can lead to dangerous iron overload 2, 4
- Don't overlook combined disorders - thalassemia carriers can develop concurrent iron deficiency, complicating the diagnostic picture 2, 4
- Don't rely solely on MCV/MCH to exclude iron deficiency - normal values do not exclude empty iron stores, particularly in early iron deficiency where anisocytosis and increased percentage of microcytic cells occur before MCV drops 6, 5
- Don't miss coexisting macrocytosis - when microcytosis and macrocytosis coexist (such as combined B12/folate deficiency with iron deficiency), they may neutralize each other and result in falsely normal MCV 2