What is the management approach for a patient with elevated Mean Corpuscular Hemoglobin Concentration (MCHC) and an otherwise normal Complete Blood Count (CBC)?

Management of Elevated MCHC with Otherwise Normal CBC

Elevated MCHC is most commonly a laboratory artifact rather than a true pathological condition and requires verification before extensive workup.

Understanding MCHC Elevation

Mean Corpuscular Hemoglobin Concentration (MCHC) is a calculated parameter that represents the average concentration of hemoglobin in a given volume of packed red blood cells. When elevated with otherwise normal CBC parameters, it typically indicates one of several possibilities:

Common Causes of Falsely Elevated MCHC

1. Cold agglutination

   • RBC clumping at room temperature causes falsely decreased RBC count and hematocrit while hemoglobin remains accurate 1
   • Results in artificially elevated MCHC calculation

2. Lipid interference

   • Lipemia can interfere with optical measurements 2

3. Hemolysis in sample

   • In vitro hemolysis during collection or processing

4. Optical interference

   • Presence of Heinz bodies, abnormal proteins, or other substances 2

Diagnostic Approach

Step 1: Verify the Abnormal Result

• Repeat the CBC with a fresh sample
• Request that the laboratory warm the sample to 37°C before analysis if cold agglutination is suspected 3
• Examine peripheral blood smear for RBC clumping, which would disappear after warming to 37°C 1

Step 2: If MCHC Remains Elevated After Verification

• Check for hemolysis indicators:

  • Elevated LDH
  • Decreased haptoglobin
  • Elevated indirect bilirubin
  • Reticulocytosis

• Consider additional tests based on clinical suspicion:

  • Direct antiglobulin test (Coombs) to rule out immune-mediated hemolysis
  • Serum iron studies (serum iron, ferritin, transferrin saturation) 4
  • Hemoglobin electrophoresis if hemoglobinopathy suspected

Management Algorithm

1. For Confirmed Laboratory Artifact:

   • Document as artifact
   • No further workup needed
   • Repeat CBC with proper technique if clinically indicated

2. For True Elevation with Evidence of Hemolysis:

   • Refer to hematology for evaluation of hemolytic anemia
   • Consider testing for cold agglutinin disease, especially with history of recent infection 1

3. For Isolated MCHC Elevation with No Evidence of Hemolysis:

   • Monitor with repeat CBC in 4-8 weeks
   • Consider iron studies to rule out early iron deficiency that may not yet affect other CBC parameters 4

Important Considerations

• An isolated elevated MCHC with truly normal other parameters rarely represents significant pathology 2
• The most recent evidence suggests that using newer analyzer parameters like RBC-O and HGB-O (optical measurements) can help differentiate between artifact and true pathology 2
• Avoid unnecessary extensive workups for what is most commonly a laboratory artifact

Common Pitfalls to Avoid

• Overlooking pre-analytical factors (sample handling, processing time)
• Failing to repeat the test before extensive workup
• Misinterpreting a single elevated MCHC as indicative of significant pathology
• Ordering extensive hematologic workups without first confirming the abnormality is genuine

Remember that while most cases of isolated elevated MCHC represent laboratory artifacts, careful verification is essential to avoid missing rare but significant hematologic conditions.