Immune-Mediated Hemolytic Anemia

What is Immune-Mediated Hemolytic Anemia?

Immune-Mediated Hemolytic Anemia (IMHA) is a serious and often life threatening disorder in dogs and cats.  IMHA results from an inappropriate immune response to the animals own red blood cells.  IMHA can be classified as primary or secondary.  With primary IMHA, the immune system malfunctions and begins to treat the red blood cells as if they were foreign invaders and begins to produce antibodies against the red blood cells.  This response is similar to what would occur against bacteria.  No underlying cause for this inappropriate reaction can be identified.  With secondary IMHA, an underlying disease condition such as infection, parasites, cancer or a reaction to a drug or vaccine causes a change in the red blood cells, which in turn stimulates the immune system to attack the cells.  The antibody response to the red blood cells can also cause “autoagglutination”, a condition where the red blood cells stick together like a cluster of grapes.  Autoagglutination is often associated with clotting disorders including pulmonary thromboembolism (PTE), which are blood clots in the lungs.  Destruction of red blood cells is termed “hemolysis” and it can occur within the blood vessels (intravascular hemolysis) or in other parts of the body, primarily the spleen, liver and bone marrow (extravascular hemolysis).  Intravascular hemolysis tends to be more severe and carries a worse prognosis than extravascular hemolysis.    Hemolysis of the red blood cells is very serious, as these cells are responsible for carrying oxygen to the entire body.  The relative amount of red blood cells circulating in the blood is measured as the packed cell volume (PCV).  A blood sample is put into a small tube and spun in a centrifuge to separate the red cells from the liquid portion of the blood and the white blood cells.  The red cells can then be measured.  The PCV is an important factor in monitoring patient improvement or decline.

Who is at risk?

Both dogs and cats can develop IMHA.  Cats very rarely get primary IMHA, but are more commonly affected secondarily to underlying diseases such as viral or parasitic infections.   Dogs more commonly have primary IMHA.  Middle aged, female dogs are at highest risk and certain breeds seem to be over represented.  Cocker spaniels, English Springer spaniels, Collies, Poodles, Old English sheepdogs, Irish setters and Dachshunds appear to be at higher risk than other breeds.  More cases of IMHA are reported to occur in the spring and summer (especially the months of May and June) than at other times of the year. The reason behind why age, breed or season plays a role is unclear. 

What are the clinical signs?

The clinical signs of IMHA vary depending on the severity and type of hemolysis involved.  Clinical signs might be acute or more gradual in onset.  The most common signs include decreased appetite, lethargy, pale gums and tongue, panting, exercise intolerance and weakness.  These signs are primarily caused by inadequate oxygen delivery to the body secondary to the decreased PCV.  Vomiting and diarrhea might also occur, but are less common.  The animal may also appear jaundiced.  Breakdown of hemoglobin from the red blood cells results in the pigment “bilirubin” to circulate in the blood.  This pigment makes the skin and eyes of the animal appear yellow and the urine might also be a dark yellow or orange in color.  If the hemolysis is occurring rapidly, the urine may appear red.

How is immune-mediated hemolyitc anemia treated?

Treatment of IMHA includes supportive therapy to address the anemia, dehydration and secondary complications as well as therapy aimed specifically at the disease.  Supportive therapy includes initial stabilization of the patient.  The patient may require one or more blood transfusions to increase the ability to deliver oxygen to the tissues of the body.  Blood transfusions aren’t without risk.  The immune system is already seeing the animal’s own red blood cells as foreign and can attack the donors cells as well.  This might initially make the hemolysis worse, although more recent research suggests this may mot be as severe as we once believed. Transfusions may also increase the risk of PTE.  It is important to weigh the benefit against the risk, but if the patient is showing signs that the body is inadequately oxygenated, a transfusion should be given.  Intravenous fluid therapy is also important to assure the patient doesn’t become dehydrated and to continually flush the kidneys, as the breakdown products of hemolysis can do permanent damage to the kidneys.  Specific drug therapy is aimed at suppressing the immune system in an effort to spare the existing red blood cells and give the bone marrow a chance to produce new red blood cells.  The cornerstone of drug therapy is corticosteroids, such as prednisone or dexamethasone.  Your veterinarian may also use other drugs in addition to corticosteroids in attempt to get the disease under control.  Different drug combinations are prescribed on a case-by case basis, depending on severity of the disease and initial response to drug therapy.  The goal with drug therapy is to slowly decrease the doses of the medications to a low level where the immune system is kept in check and the PCV is maintained in the normal range.  Some patients are able to discontinue drug therapy all together after a period of time.

What are the complications?

Complications associated with IMHA are very serious and can be broken down into those associated with the disease itself and those that can be attributed to the drug therapy.   The disease itself predisposes the patient to clotting disorders including PTE or the inability to clot properly.  PTE prevents adequate oxygen exchange between the lungs and the red blood cells and may be fatal.  Disseminated intravascular coagulopathy (DIC) is a condition that ultimately results in the animal’s inability to clot and may cause them to bleed abnormally.  Other complications include kidney failure secondary to damage from hemoglobin, which is released with destruction of the red blood cells.  Drug-related complications are most commonly secondary to immunosuppression.  The patient is at higher risk for infections, including those caused by bacteria, fungi and protozoa.  In these cases, infection can quickly spread throughout the body. Another complication is refractory anemia, where the animal doesn’t respond to the drug therapy.  The drugs, themselves have related side effects.  Corticosteroids can cause gastrointestinal upset and ulceration.  Other chemotherapy drugs used in the treatment of this disease may cause stomach upset or bone marrow problems.  The goal of therapy however is to use the lowest drug dose that will control the disease and minimize these side effects.  Any of the above side effects can be detrimental, so close patient monitoring and frequent blood work are necessary.


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