University of Virginia Health System

Hemagglutination

Peripheral blood smear, Wright-Giemsa stain, 500x

Description:

Red cell clusters (aggregates) of variable size. Distinguished from rouleaux which appear as single chains of red cells. A variable degree of spherocytosis and polychromatophilia usually present and erythrophagocytosis by neutrophils may be seen.

Pathobiology:

The agglutination is the result of autoantibodies, usually IgM and cold reacting, on the red cell surface. Complement fixation also occurs resulting in intravascular hemolysis. The antibodys specificity in most cases is "I" but may be "i". In paroxysmal cold hemoglobinuria the antibody is IgG with P specificity. The temperature amplitude at which the cold reacting antibodies attach to the red cell membrane is variable. The higher the amplitude, the more severe are the clinical manifestations.

Differential diagnosis:

• Chronic cold hemagglutinin disease
  • Monoclonal, e.g. Waldenstrom's macroglobulinemia
  • Polyclonal, e.g. usually idiopathic
• Acute, self-limited, cold hemagglutinin disease
  • Infections, e.g. Mycoplasma pneumoniae (anti-I), infectious mononucleosis (anti-i)
• Paroxysmal cold hemoglobinuria (hemagglutination much less pronounced)
  • Viral infections in children (mostly upper respiratory)
  • Tertiary syphilis
  • Primary (idiopathic)
• Severe cases of warm autoimmune hemolytic anemia

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