Low MCHC with Otherwise Normal CBC
A low MCHC with an otherwise normal CBC most commonly represents early iron deficiency before other red cell parameters become abnormal, and warrants iron studies (serum ferritin and transferrin saturation) to confirm the diagnosis. 1, 2
Understanding the Clinical Significance
MCHC is a late marker of iron deficiency that typically decreases only after other parameters have already changed. The finding of an isolated low MCHC is somewhat unusual because iron deficiency typically follows a predictable sequence:
- First stage: Anisocytosis (elevated RDW) and increased percentage of microcytic cells appear, while hemoglobin remains normal and transferrin saturation falls below 32% 3
- Second stage: MCV and MCH decline, hemoglobin becomes subnormal (though usually not below 9 g/dL), and transferrin saturation drops below 16% 3
- Final stage: MCHC decreases, hemoglobin falls below 9 g/dL, and transferrin saturation remains below 16% 3
MCH is generally a more reliable marker of iron deficiency than MCHC because it is less dependent on storage conditions and the counting machine used, and a reduction occurs in both absolute and functional iron deficiency. 4
Recommended Diagnostic Workup
Obtain iron studies to confirm or exclude iron deficiency:
- Serum ferritin is the single most useful marker, with levels <30 μg/L confirming iron deficiency in the absence of inflammation 4, 1
- Transferrin saturation <15-16% supports iron deficiency and is less affected by inflammation than ferritin 4
- Consider C-reactive protein if ferritin is borderline, as ferritin is an acute phase reactant that can be falsely elevated in inflammatory conditions 4, 2
Measure reticulocyte count to evaluate bone marrow response to any underlying anemia 4, 1
Important Clinical Pitfalls
Normal hemoglobin and hematocrit do not exclude iron depletion. Individuals with normal CBC parameters except for low MCHC may have depleted iron stores and can quickly develop iron deficiency anemia if not detected early. 5
Ferritin interpretation requires clinical context:
- In the presence of inflammation, chronic disease, malignancy, or liver disease, ferritin can be falsely elevated, potentially masking iron deficiency 4, 2
- In hemodialysis patients, ferritin levels are particularly difficult to interpret in isolation due to its role as an acute-phase reactant 4
If iron deficiency is confirmed, investigate the underlying cause:
- In adult men and postmenopausal women, iron deficiency should prompt careful assessment for gastrointestinal bleeding 4, 2
- In premenopausal women, consider menstrual losses, but still evaluate for other sources if losses seem disproportionate 4
Alternative Considerations
If iron studies are normal, consider:
- Hemoglobinopathies (such as thalassemia trait): Obtain hemoglobin electrophoresis, particularly in patients with appropriate ethnic background 4
- Chronic disease: Assess for underlying inflammatory conditions 4
- Laboratory artifact: Repeat testing to confirm the finding, as MCHC can be affected by sample storage and technical factors 4