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 Confirmed by Additional Testing

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

Analysis of Initial Blood Typing Results

The initial ABO/D typing showed:

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

This presents a discrepancy between forward and reverse typing. For a patient with type O blood, we would expect to see agglutination with both A1 and B cells in reverse typing.

Interpretation of Additional Testing

The additional testing reveals:

• Patient serum at room temperature (RT): 1+ agglutination with both A1 and B cells
• Patient serum at 4°C: 4+ agglutination with both A1 and B cells
• Autologous control at 4°C: No agglutination (0)

These results clearly demonstrate:

1. Temperature-dependent agglutination (stronger at 4°C than at RT)
2. Non-specificity (reacts with both A1 and B cells)
3. Absence of autoagglutination (negative autologous control)

These findings are classic for cold agglutinins, which are typically IgM antibodies that react optimally at cold temperatures (4°C) and have reduced activity at warmer temperatures. 1, 2

Clinical Correlation

The patient's presentation with severe anemia is consistent with cold agglutinin disease (CAD), which can cause hemolytic anemia through complement-mediated mechanisms. Cold agglutinins bind to red blood cell antigens at low temperatures and activate the classical complement pathway, resulting in hemolysis. 1

Diagnostic Implications

The diagnosis of cold agglutinin disease is supported by:

• Positive cold agglutinin reaction at 4°C (4+ agglutination)
• Activity still present but reduced at room temperature (1+ agglutination)
• Negative autologous control (ruling out autoagglutination)
• Clinical presentation of anemia 2

Important Considerations

1. Underlying conditions: CAD is often associated with:

   • Lymphoproliferative disorders (Waldenström's macroglobulinemia, lymphoma)
   • Infections (Mycoplasma, viral infections)
   • Autoimmune disorders 1, 3

2. Further testing needed:

   • Direct Coombs test (DAT) for C3d
   • Cold agglutinin titer measurement
   • Evaluation for underlying lymphoproliferative disorders
   • Serum protein electrophoresis 1

3. Transfusion implications:

   • Blood warming may be necessary for any transfusions
   • Extended red cell antigen matching beyond ABO/RhD may be beneficial 4
   • Special handling of blood samples (keeping warm during transport and testing)

Management Considerations

For this 97-year-old patient with severe anemia due to cold agglutinins:

• Keep the patient warm
• Consider rituximab as first-line therapy if treatment is needed
• Avoid corticosteroids as they are generally ineffective in CAD
• Monitor for hyperviscosity symptoms if IgM levels are elevated 1, 2

The laboratory should be notified about the presence of cold agglutinins to ensure proper handling of future blood samples, including pre-warming techniques for accurate blood typing and cross-matching.