What is the most likely calculated Red Blood Cell (RBC) parameter that would alert to possible cold agglutinin interference on virtually all automated cell counters?

Mean Corpuscular Hemoglobin Concentration (MCHC) is the Most Likely Calculated RBC Parameter to Alert for Cold Agglutinin Interference

An elevated Mean Corpuscular Hemoglobin Concentration (MCHC) above 36 g/dL is the most likely calculated RBC parameter that would alert to possible cold agglutinin interference on virtually all automated cell counters.

Understanding Cold Agglutinin Interference in Automated Cell Counters

Cold agglutinins are autoantibodies (typically IgM) that cause red blood cells to agglutinate at temperatures below body temperature. This agglutination creates several characteristic laboratory abnormalities that can be detected on automated cell counters:

Key Laboratory Findings in Cold Agglutinin Interference:

1. Elevated MCHC (>36 g/dL):

   • When RBCs agglutinate, they are counted as fewer but larger cells
   • Hemoglobin measurement remains accurate
   • Hematocrit (calculated from RBC count and MCV) becomes falsely decreased
   • This creates a mathematical discrepancy where MCHC (Hb/Hct) becomes abnormally elevated 1, 2

2. Associated abnormalities:

   • Falsely decreased RBC count (due to agglutinated cells being counted as single cells)
   • Falsely increased MCV (mean corpuscular volume)
   • Falsely decreased hematocrit
   • Normal hemoglobin concentration (typically unaffected)

Why MCHC is the Key Parameter

MCHC is particularly valuable as an indicator because:

1. It rarely exceeds 36 g/dL in any true pathological condition 2
2. Values above this threshold strongly suggest a pre-analytical error
3. The discrepancy between normal hemoglobin and falsely low hematocrit creates this characteristic elevation 1

Confirming Cold Agglutinin Interference

When cold agglutinin interference is suspected based on elevated MCHC, confirmation can be achieved by:

1. Examining a peripheral blood smear for RBC agglutination 3
2. Warming the sample to 37°C and repeating the analysis 1, 4
3. Using alternative measurement methods like the optical reticulocyte (RET) channel on Sysmex analyzers 4

Clinical Significance

Cold agglutinins can be associated with:

• Primary cold agglutinin disease
• Secondary causes including infections, malignancies, and autoimmune disorders 5
• Trauma patients may also demonstrate cold agglutinin activity 6

Practical Approach to Suspected Cold Agglutinin Interference

1. Recognize the pattern: Elevated MCHC (>36 g/dL), decreased RBC count, increased MCV, and normal hemoglobin
2. Examine peripheral blood smear for RBC agglutination
3. Warm the sample to 37-41°C for 1-120 minutes 4
4. Repeat the CBC analysis on the warmed sample
5. Consider clinical context for potential underlying causes

Pitfalls to Avoid

1. Failing to recognize the characteristic pattern of abnormalities
2. Misinterpreting the falsely low RBC count and hematocrit as true anemia
3. Initiating unnecessary workup or treatment based on spurious results
4. Inadequate warming of samples (41°C for 1 minute may be more effective than 37°C for longer periods) 4

While most automated cell counters will show the characteristic elevated MCHC pattern with cold agglutinins, it's important to note that some analyzers may show variations in this pattern. For example, some studies have found that certain Ortho ELT-8 counters may not consistently demonstrate the elevated MCHC despite showing other signs of cold agglutinin interference 2.