Have you ever seeing a CBC with an extremely high MCHC and MCV, with low Hct, low RBC count, but completely normal hemoglobin?

Before blaming the CBC analyzer, Check sample Temperature!

What is Cold Agglutination?

Cold agglutination is a phenomenon where cold-reactive autoantibodies, most commonly IgM, bind to the surface of Red blood cells when exposed to lower temperatures (typically bellow 30-37 C). this binding causes red blood cells to clump together (agglutinate). Under the microscope, a peripheral blood smear will reveal irregular clusters or clumps or red blood cells. Laboratory staffs must carefully differentiate this from Rouleaux Formation, where red blood cells stack like coins. Unlike Rouleaux, cold agglutinates reaction is completely reversible with warming. 

How does it affect CBC values?

Automated hematology analyzers count individual cells based on optical or electrical impedance. When red blood cells are clumped together, the analyzer misinterprets the clusters as single, oversized cells, throwing off multiple parameters:

• RBC Count: Falsely decreased (because clumps are counted as single units).

• Hematocrit (HCT): Falsely decreased

• MCV (Mean Corpuscular Volume): Falsely increased (due to the large size of the measured clumps).

• MCH & MCHC: Falsely increased (calculated using the falsely low RBC and HCT while hemoglobin remains accurate).

• Hemoglobin: Remains accurate 

What Should you do if you encounter such a sample?

If you spot a gritty, clumpy appearance along the walls of an EDTA collection tube paired with an illogical CBC profile and an elevated MCHC (> 

36 g/dL) you should suspect cold agglutination. Never force or blindly report discordant results. Always correlate automated data with a peripheral smear review.

How Can the Laboratory Correct the Problem?

Resolving analytical interference caused by cold agglutinins requires restoring physiological warmth to the specimen:

1. Warm the Sample: Incubate the EDTA tube at 37∘C for 15–30 minutes.

2. Mix Gently: Ensure the sample is thoroughly and gently resuspended after warming.

3. Reanalyze: Repeat the CBC analysis and review a fresh smear to confirm that the RBC clumps have dispersed and parameters have normalized.

4. Pre-Analytical Care: For known cases, maintain strict thermal control by keeping samples warm from collection straight through to analysis. Note that blood grouping can also be affected (e.g., falsely typing an O positive patient as AB positive) and requires washing cells with warm saline.

edx.org                                                                               Class Central                                                                        Coursera

                                                    StudyMls                                                            Human.BioDigital