Cold agglutinin disease (CAD)



A subtype of anemia in which abnormal bone marrow cells (called cold agglutinins) activate an immune system mechanism called the complement pathway, resulting in the destruction of red blood cells as they are attacked by antibodies. There are two forms of the condition: primary, when the cause is unknown, and secondary when there is a known disease or illness associated with the condition’s onset.

Common Symptoms

Fatigue, weakness, pallor, dizziness, palpitations, shortness of breath, darker urine, sweating, coldness of the fingers and/or toes, swollen lymph nodes, and painful bluish/reddish discoloration of the skin (fingers, ankles, wrists).

Coexisting Diseases and Conditions

Jaundice, dyspnea (difficult or labored breathing), acrocyanosis (bluish discoloration of the extremities), Raynaud’s, hemolysis, mycoplasma infection, mumps, cytomegalovirus, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, monoclonal gammopathy of unknown significance, infectious mononucleosis (Epstein Barr Virus), systemic lupus erythematosus, rheumatoid arthritis, and heart arrhythmias.

Risk Factors and Prevalence

The age group most commonly affected by CAD is between 41 and 83. Having certain infectious diseases, immunoproliferative diseases, or connective tissue diseases is a risk factor.

Females experience CAD twice as often as males do and those who live in colder climates tend to be diagnosed with it more often.


  1. Article Sources
    1. Cold agglutinin disease | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. (n.d.). Https://Rarediseases.Info.Nih.Gov/Diseases/6130/Cold-Agglutinin-Disease. Retrieved July 12, 2021, from

    2. Cold Agglutinin Disease. (n.d.). NORD (National Organization for Rare Disorders). Retrieved July 12, 2021, from