Immune Mediated Hemolytic Anemia

Immune mediated hemolytic anemia (IMHA, IMA) is a hematologic disease characterized by destruction of normal red blood cells (RBC) or destruction of RBC (hemolysis) with antigens on surface. IMA can occur in any age animal but young adults are most commonly affected. Females are affected more often than males, especially in Cocker Spaniels. IMA may occur alone, or with other immune disorders. When both RBC and platelets are destroyed the disease is called Evans syndrome.

There are several types of IMA. The most common type of hemolytic anemia is the extravascular removal of RBC that have antibodies on their surface. The antibody-coated RBCs are removed by the mononuclear phagocytic system in the spleen, bone marrow and liver. The antibody on the RBC may be directed against normal components of the RBC in which the anemia is called primary, or the antibody may be directed against a non-RBC antigen "stuck" on the cell surface. This form of hemolytic anemia is called secondary. Most often the antigen on the RBC surface cannot be identified. Animals with extravascular hemolysis DO NOT have hemoglobinemia or hemoglobinuria, but jaundice and elevated levels of bilirubin in the urine (bilirubinuria) can be present depending upon the rate of hemolysis and ability of the liver to handle the bilirubin generated from degraded RBC. Some of these patients will have intravascular agglutination of RBC.

Intravascular hemolysis occurs when complement-fixing antibodies on RBC cause RBC destruction and release of free hemoglobin into the blood. The released hemoglobin is bound to a carrier protein, haptoglobin. When all the haptoglobin is bound to hemoglobin, any free (unbound) hemoglobin will cross the glomerulus and cause hemoglobinuria in the urine), indicating hemolysis of erythrocytes within the vascular system. Hemoglobinemia and hemoglobinuria are observed in patients with intravascular hemolysis. These patients are at high risk for development of disseminated intravascular coagulation, thrombosis and renal failure from cell products released from destroyed RBCs.

There are two rare conditions in which antibodies against RBC are only active at reduced temperatures. One type results in anemia and skin lesions only in cold weather as the RBC agglutinate in the extremities and impair blood flow. The other form is characterized by anemia and hemoglobinuria in cold weather. Common signs of immune mediated hemolytic anemia include pale mucous membranes, weakness or depression. Fever is variable. Jaundice can be present in patients with either intravascular or extravascular hemolysis. Enlargement of the liver or spleen are variably present. Because IMA can be secondary to other diseases (infections, tumors, drug reactions) or may be a part of systemic lupus erythematosus (SLE). A complete evaluation of the patient is indicated, while a complete history may yield clues as to triggering factors. Evaluation might include complete blood count (CBC), urine tests, biochemical screen, radiographs, and ultrasound tests. If multiple organs appear to be affected, a test is indicated to evaluate for SLE.

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Treatment involves removal of the cause if known, supportive care and the administration of immune suppressive drugs. Supportive care should include fluid therapy if the animal is not eating and drinking. Blood transfusions may be necessary if the animal is showing signs of hypoxia at rest. Corticosteroids, usually prednisone or prednisolone are most commonly used in the treatment of hemolytic anemia. Corticosteroids suppress destruction of RBC and may have an effect on antibody production. If the patient responds favorably, the dose of prednisone is gradually tapered when the volume of packed red blood cells (PCV) stabilizes. The entire course of therapy is often several months. Failure to respond to prednisone or unacceptable side effects of prednisone may necessitate the use of other immune suppressive drugs such as cyclophosphamide, azathioprine or cyclosporine.


  1. Diane Morgan. Good Dogkeeping
  2. Malathi Raghavan, DVM, PhD, Nita Glickman, MS, MPH, George McCabe, PhD, Gary Lantz, DVM and Lawrence T. Glickman, VMD, DrPH. Diet-Related Risk Factors for Gastric Dilatation-Volvulus in Dogs of High-Risk Breeds
  3. Gingival overgrowth in a dog that received long-term cyclosporine for immune-mediated hemolytic anemia

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