Do the results of the additional testing confirm that cold agglutinins (antibodies that react with red blood cells at low temperatures) are the cause of the ABO discrepancy in this patient with severe anemia?

Cold Agglutinin Disease Confirmation in ABO Discrepancy

Yes, the additional testing results strongly confirm that cold agglutinins are the cause of the ABO discrepancy in this 97-year-old female with severe anemia. 1

Analysis of Blood Typing Results

The initial blood typing showed:

• Forward typing: Negative reactions with Anti-A and Anti-B (0)
• Strong positive reaction with Anti-D (4+)
• Reverse typing: No agglutination with A1 and B cells (0)

This creates an ABO discrepancy because:

• Forward typing suggests O blood type
• Reverse typing shows absence of expected anti-A and anti-B antibodies

Confirmation from Additional Testing

The additional testing provides clear evidence of cold agglutinins:

1. Temperature-dependent reactivity:

   • At room temperature (RT): Patient serum shows weak (1+) agglutination with both A1 and B cells
   • At 4°C: Patient serum shows strong (4+) agglutination with both A1 and B cells 1

2. Negative autologous control: This indicates that the antibodies are not reacting with the patient's own cells at 4°C, supporting the presence of non-specific cold agglutinins rather than autoantibodies 1

Clinical Correlation

These findings are classic for cold agglutinin disease (CAD), which:

• Causes hemolytic anemia through complement-mediated mechanisms
• Features antibodies (typically IgM) that agglutinate red blood cells at low temperatures
• Shows decreased activity as temperature increases 1, 2

The pattern observed in this patient is diagnostic:

• Strong reactivity at cold temperatures (4°C)
• Reduced but still present reactivity at room temperature
• Negative autologous control 1

Implications for Blood Banking

This cold agglutinin interference explains:

• The ABO discrepancy in the initial testing
• The severe anemia in this elderly patient
• The absence of expected antibodies in reverse typing 3

Management Considerations

For this 97-year-old patient with confirmed cold agglutinins:

• Blood sampling precautions: Samples should be kept warm during transport and testing to prevent in vitro hemolysis 1
• Transfusion considerations: If transfusion is needed, blood warming will be necessary, and extended red cell antigen matching beyond ABO/RhD may be beneficial 1
• Diagnostic workup: Further evaluation should include:
  • Direct Coombs test for C3d
  • Cold agglutinin titer measurement
  • Evaluation for underlying conditions (lymphoproliferative disorders, infections) 1, 2

Common Pitfalls to Avoid

1. Misinterpreting as ABO incompatibility: The discrepancy is due to cold agglutinins, not true blood type incompatibility
2. Failing to warm samples: Cold agglutinin samples must be kept at 37°C during collection and testing
3. Overlooking underlying conditions: CAD is often associated with lymphoproliferative disorders, infections, or autoimmune diseases that require investigation 1, 4
4. Inappropriate treatment: Unlike warm autoimmune hemolytic anemia, corticosteroids are generally not effective for primary CAD 2

The temperature-dependent pattern of agglutination with negative autologous control is pathognomonic for cold agglutinins as the cause of this patient's ABO discrepancy and anemia.