What parameter is most relevant when elevated, indicating potential presence of spherocytes, cold agglutinins (antibodies that agglutinate at cold temperatures), or plasma turbidity (cloudiness of plasma), such as Mean Corpuscular Hemoglobin Concentration (MCHC)?

MCHC is the Parameter That Indicates Potential Presence of Spherocytes, Cold Agglutinins, or Plasma Turbidity

The correct answer is D. MCHC (Mean Corpuscular Hemoglobin Concentration). When MCHC is elevated beyond reference limits, it indicates potential presence of spherocytes, cold agglutinins, or plasma turbidity that requires operator intervention to correct erroneous results or verify the presence of spherocytes.

Why MCHC Is the Critical Parameter

MCHC represents the average concentration of hemoglobin in a given volume of packed red blood cells. Values significantly above the reference range are physiologically impossible due to limitations on hemoglobin solubility 1. When MCHC is abnormally elevated, it serves as a critical flag for laboratory professionals to investigate further.

Cold Agglutinins and MCHC

Cold agglutinin disease (CAD) is characterized by the presence of antibodies that cause red blood cell agglutination at temperatures lower than normal body temperature 2. This agglutination leads to:

• Falsely low red blood cell (RBC) count
• Falsely low hematocrit (HCT)
• Relatively normal hemoglobin (HGB) values
• Markedly elevated MCHC values (often >100 g/dL) 3, 4

The mechanism behind this phenomenon is that when RBCs agglutinate, they are counted as single cells by automated analyzers, artificially lowering the RBC count and hematocrit while the hemoglobin measurement remains accurate, resulting in an artificially high MCHC 5.

Plasma Turbidity and MCHC

Plasma turbidity, which can occur in conditions like hyperlipidemia or paraproteinemias (such as Waldenström's macroglobulinemia), can interfere with hemoglobin measurement, leading to falsely elevated MCHC values 6. In Waldenström's macroglobulinemia, the presence of monoclonal IgM can cause plasma turbidity and may also be associated with cold agglutinins 6.

Spherocytes and MCHC

Spherocytes are abnormally shaped red blood cells that have lost their biconcave shape and become spherical. This shape change results in a higher concentration of hemoglobin per unit volume, leading to an elevated MCHC. The presence of significant numbers of spherocytes is an important diagnostic finding in certain hemolytic anemias.

Laboratory Intervention When MCHC Is Elevated

When MCHC is elevated beyond reference limits, laboratory professionals should:

1. For suspected cold agglutinins:

   • Warm the blood sample to 37°C and repeat the analysis 3, 7
   • Use specialized methods such as the reticulocyte channel warmed to 41°C on modern analyzers 7

2. For suspected plasma turbidity:

   • Evaluate the sample for lipemia or paraproteinemia
   • Consider alternative methods for hemoglobin measurement

3. For suspected spherocytosis:

   • Perform a careful examination of the peripheral blood smear
   • Look for the characteristic appearance of spherocytes

Why Other Parameters Are Not the Answer

• A. HGB (Hemoglobin): Hemoglobin measurement is generally reliable even in the presence of cold agglutinins 5. It's the discrepancy between hemoglobin and hematocrit that helps identify the problem, not the hemoglobin value itself.

• B. WBC (White Blood Cell Count): WBC count is typically not affected by cold agglutinins or plasma turbidity 5.

• C. MCV (Mean Corpuscular Volume): While MCV may be affected by cold agglutinins (usually falsely elevated), it is not as consistently or dramatically affected as MCHC, which serves as a more reliable indicator of these pre-analytical issues 4.

In conclusion, MCHC is the most sensitive parameter for detecting the presence of cold agglutinins, plasma turbidity, or significant spherocytosis, making it the critical value that laboratory professionals must address when it exceeds reference limits.