What does a variation in Mean Corpuscular Hemoglobin Concentration (MCHC) in a Complete Blood Count (CBC) indicate?

Understanding Variations in Mean Corpuscular Hemoglobin Concentration (MCHC) in a CBC

Variations in MCHC on a Complete Blood Count (CBC) can indicate several clinical conditions ranging from true hematologic disorders to laboratory artifacts, with both decreased and elevated values having distinct clinical significance.

What is MCHC?

MCHC is a calculated parameter that measures the average concentration of hemoglobin in a given volume of packed red blood cells. It is calculated using the formula:

MCHC = Hemoglobin (g/dL) ÷ Hematocrit × 100

Decreased MCHC Values

Clinical Significance:

• Iron Deficiency Anemia: Characterized by microcytic (low MCV) and hypochromic (low MCHC) red cells 1
• Thalassemia: Often presents with low MCHC along with microcytosis
• Anemia of Chronic Disease: May present with normocytic (normal MCV) and normochromic or hypochromic (normal or low MCHC) characteristics 2

Elevated MCHC Values

True Elevations:

• Spherocytosis: Causes increased hemoglobin concentration within RBCs
• Sickle Cell Disease: SC variant specifically shows abnormally high MCHC, contributing to sickling and hemolysis 3
• Hemoglobin C Disease: Results in dehydrated RBCs with increased MCHC

False Elevations (Laboratory Artifacts):

• Cold Agglutinins: Cause RBC clumping that interferes with accurate measurement 4
• Lipemia: Lipid interference can falsely elevate MCHC readings 4, 5
• Hemolysis: In-vitro hemolysis releases free hemoglobin, falsely increasing MCHC
• Severe Hyperglycemia: Can affect RBC volume measurement

Diagnostic Approach for Abnormal MCHC

1. Verify the Result:

   • Check for laboratory artifacts by examining the peripheral blood smear 6
   • Consider repeat testing, especially if MCHC is significantly elevated beyond physiological limits 5

2. Correlate with Other CBC Parameters:

   • Low MCHC with low MCV suggests iron deficiency or thalassemia
   • Normal MCV with low MCHC may indicate early iron deficiency or anemia of chronic disease
   • High MCHC with normal or low MCV suggests spherocytosis or laboratory error 6

3. Additional Testing Based on Suspected Cause:

   • For suspected iron deficiency: Iron studies (serum iron, TIBC, ferritin) 1
   • For suspected hemolysis: Reticulocyte count, LDH, haptoglobin, bilirubin
   • For suspected hemoglobinopathy: Hemoglobin electrophoresis

Special Considerations

Falsely Elevated MCHC

When MCHC is significantly above the reference range (typically >36-38 g/dL):

• Consider laboratory artifact as the most likely cause 5
• Request peripheral smear examination to confirm RBC morphology 6
• For cold agglutinin interference, warming the sample to 37°C before analysis may correct the issue 4
• For lipemic samples, plasma exchange techniques may be required 4

MCHC in Chronic Kidney Disease

• Anemia in CKD typically presents with normocytic and normochromic characteristics (normal MCHC) 2
• Hemoglobin is preferred over hematocrit for monitoring anemia in CKD as it is more stable 2

MCHC in Polycythemia

• Elevated hematocrit (>45% in men, >42% in women) with normal MCHC suggests polycythemia 2
• Iron deficiency from repeated phlebotomy in polycythemia vera patients can lead to decreased MCHC 2

Clinical Pitfalls to Avoid

1. Don't ignore significantly elevated MCHC values - they are often laboratory artifacts requiring verification but can occasionally indicate serious hemoglobinopathies 6

2. Don't diagnose iron deficiency based on MCHC alone - confirm with iron studies and other RBC indices 1

3. Don't overlook the peripheral blood smear - it remains essential for confirming the cause of abnormal MCHC, especially in pediatric cases 6

4. Don't fail to consider pre-analytical factors - sample collection, storage, and processing can all affect MCHC values 5

MCHC variations should always be interpreted in the context of other CBC parameters and clinical presentation to determine their true significance and guide appropriate management.