What is the suggested workup for a patient with low Mean Corpuscular Hemoglobin Concentration (MCHC) and normal Hemoglobin (Hb), Hematocrit (Hct), and Mean Corpuscular Volume (MCV)?

Workup for Low MCHC with Normal Hemoglobin, Hematocrit, and MCV

The recommended workup for a patient with isolated low Mean Corpuscular Hemoglobin Concentration (MCHC) and normal hemoglobin (Hgb), hematocrit (Hct), and mean corpuscular volume (MCV) should focus on iron status evaluation, with serum ferritin and transferrin saturation as the primary tests.

Initial Laboratory Assessment

The finding of isolated low MCHC with otherwise normal red blood cell parameters requires a systematic approach to identify potential causes:

1. Iron Status Evaluation:

   • Serum ferritin
   • Transferrin saturation (TfS)
   • Serum iron and total iron binding capacity (TIBC)

2. Additional Blood Parameters:

   • Red cell distribution width (RDW) - elevated RDW with normal MCV may indicate coexisting microcytosis and macrocytosis 1
   • Reticulocyte count - to assess bone marrow response 1
   • Complete blood count with differential 1
   • C-reactive protein (CRP) - to assess for inflammation 1

Interpretation and Further Testing

If Iron Deficiency Suspected:

Low MCHC may represent early iron deficiency before other parameters become abnormal. In the presence of inflammation, serum ferritin up to 100 μg/L may still be compatible with iron deficiency 1.

• If serum ferritin <30 μg/L (without inflammation) or <100 μg/L (with inflammation) and transferrin saturation <20%, diagnose iron deficiency 1
• Consider peripheral blood smear examination for hypochromic red cells 1

If Normal Iron Studies:

Consider these additional tests:

• Vitamin B12 and folate levels - deficiencies can affect hemoglobin synthesis 1
• Evaluation for chronic inflammation - can affect iron utilization 1
• Hemoglobin electrophoresis - to rule out hemoglobinopathies
• Liver function tests - liver disease can affect protein synthesis

Special Considerations

1. Pre-analytical Factors:

   • Verify sample integrity - prolonged storage can falsely lower MCHC 2
   • Confirm timing of blood draw - MCHC values can decrease significantly after 8 hours of storage, especially at room temperature 2

2. Technical Factors:

   • Consider instrument calibration issues - isolated MCHC abnormalities may reflect analyzer variation
   • Request repeat testing if clinically indicated

3. Clinical Context:

   • Assess for symptoms of iron deficiency even with normal hemoglobin
   • Review medication history for drugs that might affect red cell parameters
   • Consider recent blood donations or occult blood loss

When to Consider Hematology Consultation

Hematology consultation should be considered if:

• Initial workup is inconclusive
• MCHC remains persistently low despite normal iron studies
• Patient has other unexplained hematologic abnormalities
• Peripheral blood smear shows significant morphologic abnormalities 1

Pitfalls to Avoid

1. Overlooking early iron deficiency - Low MCHC may be the earliest indicator of iron deficiency before anemia develops 3

2. Assuming normal hemoglobin excludes iron deficiency - Iron stores can be depleted with normal hemoglobin levels 1

3. Relying solely on MCV - MCH and MCHC may be more sensitive than MCV for detecting early iron deficiency 3

4. Ignoring sample handling - MCHC is particularly susceptible to pre-analytical variables; improper storage can affect results 2

5. Missing mixed deficiency states - Concurrent B12/folate deficiency and iron deficiency can result in normal MCV with low MCHC 1

By following this systematic approach, clinicians can effectively evaluate patients with isolated low MCHC and determine appropriate management based on the underlying cause.