Immune-Mediated Hemolytic Anemia

What is Immune-Mediated Hemolytic Anemia (IMHA)?

Immune-mediated hemolytic anemia occurs when a patient’s own immune system starts to attack the body’s red blood cells (RBCs). When too many red blood cells are destroyed, the patient develops an abnormally low red blood cell count, also called anemia. The primary function of the red blood cell is to transport oxygen to the tissues, and when this oxygen transport decreases to a critical level, clinical signs occur. IMHA can be primary (no known cause identified) or can be secondary to a detectable cause such as infections, drug reactions, blood parasites, cancer, or inherited red blood cell defects.

Who gets IMHA?

Immune-mediated hemolytic anemia is diagnosed much more commonly in dogs than in cats. Any dog or cat can develop IMHA, but female dogs and certain breeds of dogs are predisposed including Cocker and Springer Spaniels, Old English Sheepdogs, Bichon Frises, Bearded and Rough‐coated Collies, Poodles, and Flat‐coated Retrievers. In cats, IMHA is often associated with certain underlying infections including feline leukemia virus and red blood cell infections.

What are the clinical signs of IMHA? 

Clinical signs depend on the severity of the anemia and the underlying cause. Symptoms can range from mild and vague to severe and life threatening including:

• Lethargy
• Weakness
• Decreased appetite
• Labored breathing
• Pale gums
• Increased heart rate
• Fever
• Jaundice (yellow gums and/or skin and eyes)
• Vomiting
• Diarrhea
• Weight loss
• Pica (eating abnormal items such as dirt)
• Dark red or brown urine

Physical examination by a veterinarian may also detect an unusual sound between heartbeats (murmur) and an enlarged spleen. Mild symptoms can quickly progress to severe life threatening signs. Collapse, unconsciousness, or even death can occur if the anemia is severe.

How can we diagnose IMHA?

A complete history and thorough physical examination by a veterinarian are the first steps. Your veterinarian will ask you questions regarding your pet’s medical history including:

• When the signs were first noticed
• What kind of symptoms you have seen
• Which recent medications or vaccinations have been administered
• Whether your pet has recently traveled and where

Anemia is suspected when the oral mucous membranes (gums and tongue) are pale or white. Anemia is confirmed by performing a blood test that measures the red blood cell (RBC) count or the packed cell volume (PCV). Following a diagnosis of anemia, additional testing may be recommended to determine the underlying cause of the anemia including evaluation for an immune cause. Since there are many causes for anemia, more specific testing is often necessary.

Laboratory testing is also useful to determine whether new red blood cells are being produced, to evaluate the function of the body’s other organs, and to search for underlying causes (like infections or cancer). Chest X-rays (also called radiographs) and ultrasound of the abdomen may be recommended to search for underlying tumors and to further evaluate the internal organs.

How do we treat IMHA?

There are four main goals of therapy:

1. Stabilizing the patient - Hospitalization, possibly with intensive care and red blood cell transfusions, may be necessary depending on the severity of the disease process. Supplemental oxygen therapy may be necessary.
2. Treating any underlying cause for the IMHA (if detected) - Your veterinarian may discuss discontinuing any recent medications which could trigger IMHA. If an infection is suspected, an appropriate medication for the infection will be given.
3. Suppressing the immune system in order to stop the immune attack on the red blood cells - High doses of steroid medications (such as prednisone or dexamethasone) are commonly given to help control the immune attack on the red blood cells. Additional immunosuppressive drugs may also be needed, especially in more severe cases.
4. Minimizing the risk of complications from blood clots - Because the red blood cell destruction can result in blood clots, anticoagulant drugs or blood thinners like aspirin, or clopidogrel are needed. 

Newer treatments like blood purification (therapeutic plasmapheresis), special oxygen (hyperbaric) therapy, and newer drugs are being investigated.

Once immunosuppressive therapy is started, response to treatment is expected within a week if the medications are effective. Additional medications are often added if an adequate response is not detected. 

What happens to patients with IMHA after initial hospitalization or diagnosis?

The patient is placed on oral medications when tolerated, and these medications are typically given daily for at least several months. The medication doses are slowly lowered (tapered) by your veterinarian based on recheck examinations and lab tests. Rapid tapering of the medications may be more likely to result in relapse of the anemia. Unfortunately, relapses of this disease can occur even in patients that are well controlled.

What is the prognosis for pets with IMHA? 

IMHA can be a fatal disease, and 20-80% of animals either die or are euthanized as a consequence of this disease. Cats appear to have a better prognosis when compared to dogs.  The risk of mortality (death) increases if blood clots occur. For patients that respond to immunosuppressive therapy and do not need repeated transfusions, prognosis can be good. Patients that require repeated transfusions or quickly destroy transfused red blood cells have a much poorer prognosis. 

Where can I learn more about IMHA?

The specialists among the American College of Veterinary Internal Medicine have developed a consensus statement about how to diagnose as well as how to treat IMHA. Links to these scientific papers are available below.

Garden, OA, Kidd, L, Mexas, AM, et al. ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats. J Vet Intern Med. 2019; 33: 313– 334.

Swann, JW, Garden, OA, Fellman, CL, et al. ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs. J Vet Intern Med. 2019; 33: 1141– 1172.