Master Cold Agglutinin Autoimmune Hemolytic Anemia (C-AIHA) with Picmonic for Medicine

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Cold Agglutinin Autoimmune Hemolytic Anemia (C-AIHA)

Cold-ice with A-gluing Auto-in-moon Anemone
Picmonic
In cold agglutinin autoimmune hemolytic anemia, IgM autoantibodies bind to the surface of RBCs at cold temperatures, leading to intravascular hemolysis. Etiologies include idiopathic, infectious (Mycoplasma pneumoniae, EBV), CLL, lymphomas, and Waldenstrom’s Macroglobulinemia. Symptoms include acrocyanosis and livedo reticularis. Diagnosis is made by the Coombs test. Treatment involves avoiding cold temperatures as well as rituximab with or without fludarabine.

12 KEY FACTS
PATHOPHYSIOLOGY
IgM Binds to RBCs at Cold Temperatures (28-31C)
Mountain-goblin Binds to RBC at Cold-thermometer

In cold agglutinin autoimmune hemolytic anemia, IgM autoantibodies bind to RBCs at cold temperatures below normal body temperature. IgM fixes complement to the RBC surface. At body temperature, the proteins such as CD55 and CD59 on the RBC cell surface prevent the activation of the complement. However, in cold temperatures blood cannot adequately circulate to peripheral locations in the body to provide anti-complement molecules; therefore, the complement is activated in these situations.

Intravascular Hemolysis
Intravascular Hemolysing-RBC

In cold agglutinin autoimmune hemolytic anemia, the membrane attack complex (MAC) forms and compromises the RBC membrane integrity, leading to intravascular hemolysis.

Waldenstrom's Macroglobulinemia
Winter-storm with Mountain-goblin-anemone

Chronic lymphocytic leukemia, lymphoma, Waldenstrom's Macroglobulinemia, and other lymphoproliferative disorders are frequently associated with cold agglutinin autoimmune hemolytic anemia, as these patients’ RBC surfaces are more likely to contain certain antigens to which IgM cold agglutinins bind. In addition, these lymphoproliferative disorders may induce the synthesis of IgM cold agglutinins, leading to cold agglutinin autoimmune hemolytic anemia.

Mycoplasma Pneumoniae
Mic-plasma Nude-Mona

Certain infections such as Mycoplasma pneumonia have both been associated with cold agglutinin autoimmune hemolytic anemia. Mycoplasma contains a specific antigen on its surface to which IgM autoantibodies bind, causing agglutination and hemolysis.

Infectious Mononucleosis
Monkey-nuclear

EBV is a rare cause of cold agglutinin autoimmune hemolytic anemia; autoantibodies form to the i-surface antigen.

Lymphomas and CLL
Lime-foam and CaLL me crone

Chronic lymphocytic leukemia, lymphoma, Waldenstrom's Macroglobulinemia, and other lymphoproliferative disorders are frequently associated with cold agglutinin autoimmune hemolytic anemia, as these patients’ RBC surfaces are more likely to contain certain antigens to which IgM cold agglutinins bind. In addition, these lymphoproliferative disorders may induce the synthesis of IgM cold agglutinins, leading to cold agglutinin autoimmune hemolytic anemia.

SYMPTOMS
Acral Cyanosis with Cold Exposure
Acral-acorn with Cyan-crayon

Livedo reticularis may also occur with cold agglutinin autoimmune hemolytic anemia and is described as having a purple-bluish lacy or mottled appearance.

Blue Fingers and Toes
Blue Fingers and Toes

In cold agglutinin autoimmune hemolytic anemia, agglutination and hemolysis tends to occur in peripheral locations on the body such as the fingers and toes. Skin color returns back to normal in these regions once it is warmed.

DIAGNOSIS
Positive Coombs Test
Positive Comb

The Coombs test detects if a patient has formed autoantibodies to their RBCs. A Direct Coombs test involves mixing a patient’s RBCs with test serum containing anti-IgM antibodies. If a patient has cold agglutinin autoimmune hemolytic anemia, their RBCs will be coated in IgM and anti-IgM in the test serum will agglutinate the RBCs; this reaction is referred to as a positive Coombs test. The Coombs test will not demonstrate agglutination with IgG antibodies.

TREATMENT
Avoid Cold
Avoid Cold-thermometer

Because cold agglutinin autoimmune hemolytic anemia occurs below body temperature, patients should avoid the cold.

Rituximab
Red-tux-mob

Rituximab is a monoclonal antibody against B cells, some of which produce autoantibodies.

+/- Fludarabine
Fedora-bean

Rituximab is typically used in combination with other immunosuppressants or other cytotoxic agents, such as fludarabine, a purine analog.

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