Types of CAD

Cold agglutinin disease (CAD), a rare condition in which the immune system attacks red blood cells at cold temperatures, can be divided into two types: primary and secondary CAD.

The types are based on the disorder’s underlying cause. In both, the immune attack is mediated by antibodies, called cold agglutinins, which bind to red blood cells, causing them to clump together and, ultimately, die.

Either type occurs with exposure to cold temperatures, usually between 32 to 50 F (0 and 10 C).

Regardless of type, the symptoms, diagnosis, and treatment for both forms of CAD are identical.

Primary CAD

When CAD occurs in the absence of other disorders and its specific cause is unknown, it is classified as primary CAD.

This specific form of the disease is thought to be associated with the excessive proliferation of B-cells that specifically make cold agglutinins. Of note, B-cells are immune cells that are responsible for producing antibodies that normally help to defend the body from disease-causing agents.

Secondary CAD

Secondary CAD develops in people who have an underlying health condition, such as a viral or bacterial infection, cancer, or another autoimmune disorder. This specific form of the disease is thought to account for up to 70% of CAD cases. Notably, in people with secondary CAD, treating the underlying condition also can often serve to treat CAD, as both are interconnected.


Last updated: Oct. 1, 2021


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