CAD is a severe, chronic, rare blood disorder.¹ It is a type of autoimmune hemolytic anemia (AIHA), which means that the body’s immune system attacks and destroys its own red blood cells by mistake.²

Symptoms of CAD may include fatigue, dizziness, chest pain, shortness of breath, anemia, transfusion requirements, dark urine and increased risk of thrombotic events like stroke or heart attack.²

In people with CAD, autoantibodies such as immunoglobin M (IgM) cause red blood cells to clump together when extremities (nose, ears, fingers, toes) are exposed to cold temperatures or when an individual with CAD has a compromised immune system or infection.³ Then, the complement cascade, which plays an important role in the immune system, is activated to destroy heathy red blood cells in a process called hemolysis.^4,5

Excessive activation of the complement cascade can lead to the onset or progression of many diseases including CAD.^6,7

References

1. Sokol RJ, Hewitt S, Stamps BK. Autoimmune haemolysis: an 18-year study of 865 cases referred to a regional transfusion centre. Br Med J (Clin Res Ed). 1981;282(6281):2023-2027.
2. National Institute of Health (NIH), Genetic and Rare Diseases Information Center (GARD) Website https://rarediseases.info.nih.gov/diseases/6130/cold-agglutinin-disease. Accessed November 21, 2019.
3. Berentsen S, Ulvestad E, Langholm R, et al. Primary chronic cold agglutinin disease: a population based clinical study of 86 patients. Haematologica. 2006;91(4):460-466.
4. Cold agglutinin disease. Genetic and Rare Diseases Information Center Web site. https://rarediseases.info.nih.gov/diseases/6130/cold-agglutinin-disease. Accessed November 21, 2019.
5. Reynaud Q, Durieu I, Dutertre M, et al. Efficacy and safety of rituximab in auto-immune hemolytic anemia: A meta-analysis of 21 studies. Autoimmun Rev. 2015;14(4):304-313.
6. Morgan P, et al. Complement, a target for therapy in inflammatory and degenerative diseases. Nature Reviews Drug Discovery. 2015;14:857-877.
7. Markiewski MM, Lambris JD. The role of complement in inflammatory diseases from behind the scenes into the spotlight. Am J Pathol. 2007;171(3):715-727.