Cold agglutinin disease

A rare autoimmune disorder affecting red blood cells

Cold agglutinin disease
Synonyms	Cold autoimmune hemolytic anemia, CAD
Pronounce
Field	Hematology, Immunology
Symptoms	Fatigue, anemia, jaundice, cold-induced acrocyanosis, Raynaud's phenomenon
Complications	Hemolytic anemia, splenomegaly, circulatory collapse in severe cases
Onset	Often insidious; more common in older adults
Duration	Chronic (primary) or transient (secondary)
Types	Primary (idiopathic), Secondary (due to infection, malignancy, or autoimmune disease)
Causes	Autoantibodies targeting red blood cells, often triggered by cold temperatures
Risks	Mycoplasma pneumoniae infection, Epstein–Barr virus, lymphoma, autoimmune diseases
Diagnosis	Direct antiglobulin test (Coombs test), Cold agglutinin titer, blood smear, complete blood count
Differential diagnosis	Warm autoimmune hemolytic anemia, paroxysmal cold hemoglobinuria, cryoglobulinemia
Prevention	Avoidance of cold exposure, treating underlying conditions
Treatment	Warm clothing, rituximab, corticosteroids, plasmapheresis in severe cases
Medication	Rituximab, bendamustine, cyclophosphamide, folic acid supplements
Prognosis	Generally good with treatment; variable in secondary disease depending on underlying cause
Frequency	Rare; estimated incidence of 1 per million per year
Deaths	Rare, mostly in severe untreated or complicated cases

Cold agglutinin disease (CAD) is a rare autoimmune disorder characterized by the presence of cold agglutinins, which are antibodies that cause red blood cells to clump together at low temperatures. This clumping can lead to the destruction of red blood cells, a condition known as hemolytic anemia.

Pathophysiology

Cold agglutinin disease is primarily mediated by IgM antibodies that target the I antigen on the surface of red blood cells. These antibodies are most active at temperatures below normal body temperature, typically between 0°C and 30°C. When exposed to cold, these antibodies bind to red blood cells, causing them to agglutinate, or clump together. This agglutination can lead to the activation of the complement system, resulting in the destruction of red blood cells through a process called intravascular hemolysis.

Clinical Presentation

Patients with cold agglutinin disease often present with symptoms of anemia, such as fatigue, pallor, and shortness of breath. In addition, exposure to cold temperatures can lead to acrocyanosis, a bluish discoloration of the extremities, and Raynaud's phenomenon, where fingers and toes change color in response to cold or stress. Some patients may also experience hemoglobinuria, which is the presence of hemoglobin in the urine, giving it a dark color.

Diagnosis

The diagnosis of cold agglutinin disease is based on clinical presentation and laboratory findings. A complete blood count may reveal anemia, and a direct antiglobulin test (DAT) is often positive for complement. The presence of cold agglutinins can be confirmed by testing the patient's serum at different temperatures to observe agglutination of red blood cells. A cold agglutinin titer may also be performed to quantify the level of cold agglutinins.

Treatment

Management of cold agglutinin disease involves avoiding exposure to cold temperatures to prevent hemolysis. In severe cases, treatment may include immunosuppressive therapy such as rituximab, a monoclonal antibody that targets B cells, or other agents like corticosteroids. In some cases, plasmapheresis may be used to remove antibodies from the blood. Patients with significant anemia may require blood transfusions.

Prognosis

The prognosis for patients with cold agglutinin disease varies. Some individuals may experience mild symptoms and require minimal intervention, while others may have more severe disease requiring ongoing treatment. The condition is typically chronic, and management focuses on symptom control and prevention of complications.

Related pages

• Autoimmune hemolytic anemia
• Raynaud's phenomenon
• Immunoglobulin M
• Complement system

External links

Classification	ICD-10: D59.1 MeSH: D000744 DiseasesDB: 2949
External resources	eMedicine: med/408

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