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Faizan Khan: Cold Agglutinins and Their Effects on CBC Results
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Mar 26, 2026, 16:39

Faizan Khan: Cold Agglutinins and Their Effects on CBC Results

Faizan Khan, Certified Laboratory Technician (PGDMLT) at Manipal TRUtest, shared a post on  LinkedIn:

“Cold Agglutinins and Their Effects on CBC Results

Cold agglutinins are antibodies (usually IgM) that cause red blood cells (RBCs) to agglutinate (clump) at low temperatures, typically below 37 degrees Celsius.

This can significantly interfere with CBC results and produce misleading values.

Understanding this phenomenon is critical for accurate laboratory reporting

What are Cold Agglutinins?

  • Autoantibodies that bind RBCs at low temperature
  • Cause RBC agglutination (clumping)
  • Usually react at temperatures below 30–37 degrees Celsius
  • Associated with autoimmune disorders and infections

Effects on CBC Parameters

Cold agglutinins cause characteristic CBC abnormalities:

  • RBC Count causes Falsely Decreased
    Clumped RBCs are counted as single cells by analyzer
  • RBC Count causes Falsely Decreased
    Clumped RBCs are counted as single cells by analyzer
  • MCV causes Falsely Increased
    Analyzer interprets RBC clumps as large cells
  • MCH causes Falsely Increased
    Calculated parameter affected by low RBC count
  • MCHC causes Markedly Increased (Key Indicator)
    This is the most important clue for cold agglutinin interference

WBC and Platelets usually normal

But severe agglutination may affect counts

 Analyzer Flags and Findings

  • RBC agglutination flag
  • Abnormal RBC histogram
  • MCHC greater than 36 grams per deciliter (strong clue)
  • Visible RBC clumping on peripheral smear

How to Correct Cold Agglutinin Effect

  • Warm sample at 37 degrees Celsius for 15 to 30 minutes
  • Repeat CBC analysis
  • RBC parameters usually normalize

Key Laboratory Clue

Suspect cold agglutinins if:

  • High MCHC (greater than 36 grams per deciliter)
  • High MCV with low RBC count
  • Analyzer flag for agglutination

Clinical Associations

  • Cold agglutinin disease
  • Mycoplasma pneumonia infection
  • Infectious mononucleosis
  • Autoimmune hemolytic anemia
  • Lymphoproliferative disorders

Key Message for Lab Professionals

Always correlate CBC results with:

  • Peripheral smear
  • Analyzer flags
  • Clinical findings

Warming the sample can prevent reporting errors. ”

Faizan Khan: Cold Agglutinins and Their Effects on CBC Results

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