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Disorders Involving Cytotoxic Antibodies (Type II Reactions) in Horses


Ian Rodney Tizard

, BVMS, BSc, PhD, DSc (Hons), DACVM, Department of Veterinary Pathobiology, College of Veterinary and Biomedical Sciences, Texas A&M University

Reviewed/Revised Mar 2019 | Modified Oct 2022

Type II reactions occur when an antibody binds to an antigen present at the surface of the body's own cells. This activates a cell-killing series of proteins called complement, resulting in cell death and tissue damage. Type II reactions can lead to several types of diseases in horses, including anemia, blood clotting problems, and skin and muscle disorders. They may be associated with other immune system disturbances, such as cancers of the lymphoreticular system, or triggered by a drug, vaccine, or infection. Most often, the triggering cause cannot be pinpointed.

Immune-mediated Hemolytic Anemia

This type of anemia is a severe and life-threatening disease in which the immune system sees its own red blood cells as foreign invaders and destroys them. Red blood cells are manufactured as usual in the bone marrow, but once released into the bloodstream, they are attacked and destroyed by antibodies. Signs of anemia may include fatigue, paleness of the lips and gums, and depression, along with jaundice in some cases. Other signs your veterinarian may find include an enlarged liver or spleen.

Cold Agglutinin (Hemolytic) Disease

Cold agglutinin (hemolytic) disease is also called cold antibody disease. It is a type of immune-mediated hemolytic anemia in which the body develops antibodies that attack red blood cells at temperatures lower than normal body temperature. It is more common in colder climates and seasons. The cause is usually not known, but it may follow a longterm infection, another autoimmune disorder, or cancer. The red blood cells are destroyed prematurely and bone marrow production of new cells cannot compensate for their loss. The severity of the anemia is determined by the length of time that the red blood cells survive and by the capacity of the bone marrow to produce new red blood cells. Signs of hemolytic anemia (such as fatigue, pale gums, and jaundice) may be seen initially. The condition may also cause cell death in the cooler parts of the body such as the nose, tips of the ears, legs, scrotum, and the skin over the penis. Diagnosis is based on a blood test. Medications are available to help control this disease. The cause of disease, if known, is also treated. Your veterinarian can prescribe the most appropriate medication for your horse. Unfortunately, many horses die because of this condition.

Immune-mediated Thrombocytopenia

Immune-mediated thrombocytopenia is caused by the destruction of platelets (thrombocytes) by the immune system in much the same manner as red blood cells are destroyed in immune-mediated hemolytic anemia (see above). When an animal has thrombocytopenia, clotting does not occur correctly. Even minor injuries can cause uncontrollable bleeding, further decreasing the number of red blood cells. The most frequent signs are bleeding within the skin and mucous membranes (which can look like pinpoint dots or small bruises).

The diagnosis is usually made based on the signs and response to treatment, certain blood tests (such as platelet counts and clotting profiles), and bone marrow tests. Medications that suppress the immune system are used to treat this disease. Signs usually disappear after 5 to 7 days of treatment when platelet counts begin to rise. If the platelet count has not increased significantly after 7 to 10 days, additional or different medications may be prescribed. If the blood loss is life threatening, transfusions of whole blood or plasma may be necessary.

Treatment is often continued for 1 to 3 months after the platelet counts return to normal. Some animals have persistent decreases in platelets even with drug treatment. If this is the case with your horse, you will want to discuss longterm treatment and maintenance options with your veterinarian.

Autoimmune Skin Disorders

Pemphigus foliaceus is an uncommon autoimmune disease that affects the skin in horses. In affected animals, the immune system produces antibodies against the “glue” that normally keeps skin cells (keratinocytes) attached to one another. White blood cells move in, causing further damage, and the keratinocytes break apart from each other, forming pimples or crusted areas. Drugs that suppress the immune system are used to treat the disorder.

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