What is autoimmune hemolytic anemia?
Autoimmune means an immune reaction directed against the bodys own tissues, while hemolysis comes from the Greek words hemo meaning blood and lysis meaning to break open. Autoimmune hemolytic anemia (AIHA) is an immune system disease in which the body attacks and destroys its own red blood cells. In dogs with AIHA, red blood cells are still being manufactured in the bone marrow, but once released into the circulation, they have a shorter-than-normal life span.
This disease may also be called immune-mediated hemolytic anemia or IMHA.
AIHA may be primary (idiopathic) or it may be secondary.
With primary AIHA, the dogs immune system is not working properly, and it incorrectly makes antibodies that target its own red blood cells. In dogs, it is estimated that about three-quarters of cases of AIHA are primary.
With secondary AIHA, the surface of the red blood cells becomes altered by an underlying disease process or a toxin. The dogs immune system then recognizes the altered red blood cells as foreign invaders that must be destroyed. Secondary AIHA may be triggered by cancer, infection as seen with Ehrlichia or Leptospira (see handouts “Ehrlichiosis in Dogs” and “Leptospirosis in Dogs”), blood parasites such as Babesia (see handout “Babesiosis in Dogs”), drug reactions, snakebites (see handout “Snakebite Envenomization”), chemicals, toxins, or bee stings. In dogs, neoplasia or cancer appears to be the most common cause of secondary AIHA. Stressful events on the body may trigger AIHA if underlying secondary causes are already present.
Once targeted, the red blood cells are either destroyed within the blood vessels by a process called intravascular hemolysis or destroyed when they circulate through the liver or spleen by a process called extravascular hemolysis. In both situations, hemoglobin will be released; the liver will attempt to break down the excess levels of hemoglobin, increasing the workload of this organ.
Predicting disease outcome using scoring systems
Because clinical presentation and response to treatment are variable in dogs with IMHA, a number of scoring systems have been developed to estimate the severity of disease and prognosis for dogs when they are diagnosed. These scores have been generated by investigating associations between individual clinicopathological variables and outcome, measured as survival time after diagnosis or percentage mortality at a defined time point. Summaries of two different prognostic scores are presented in . In a recent study, Goggs et al14 found that a combination of the American Society of Anesthesiologists’ clinical grade and serum concentrations of bilirubin and urea or creatinine predicted mortality with greater accuracy than either of the scores described by Whelan et al16 or Ishihara et al17 in a sample of 276 dogs in the British Isles, but the authors unfortunately did not present their own model in the same form of a user-friendly score. An additional study revealed that the score developed in Japan did not predict survival in dogs with IMHA in Australia,18 highlighting the importance of using prognostic tools in a population for which they have been validated.
| Score | Parameter | Definition | Score |
|---|---|---|---|
| CHAOS (Whelan et al)16 | Age | ≥7 years | 2 |
| Rectal temperature | ≥38.9°C | 1 | |
| Persistent agglutination after dilution in saline | Positive | 1 | |
| Serum albumin concentration | <30 g/L | 1 | |
| Serum bilirubin concentration | ≥85.5 µmol/L | 2 | |
| Total possible score | 7 | ||
| Ishihara et al17 | Sex | Male | 1 |
| Season | Warm | 1 | |
| Packed cell volume | <20% | 1 | |
| Platelet count | <200×103/µL | 1 | |
| Serum total protein concentration | <6 g/dL | 1 | |
| Total possible score | 5 |
Development of “intravascular hemolysis”, a term used inconsistently to describe some combination of hemoglobinuria, hemolysed plasma, and presence of persistent agglutination of red blood cells, has traditionally been considered an indicator of a poor prognosis in dogs with IMHA. However, this perception is not supported by the majority of clinical studies of factors associated with survival: only two studies indicated using univariate analyses that autoagglutination was associated with decreased survival. One of these studies subsequently showed no difference between cases that had or did not have undefined “intravascular hemolysis”,19 while the other demonstrated that agglutination was associated with survival to discharge but not to 1 year after diagnosis.20 In contrast, serum total bilirubin concentration, which is an indicator of the severity of either intravascular or extravascular hemolysis, has been associated consistently with survival in several previous studies that utilized either univariate or multivariate analyses, albeit with considerable variation in the apparent size of the effect.10,13–15,19,21–24 Consequently, we believe that this variable is likely to be the most useful for the clinician in guiding therapy and estimating prognosis, particularly because it is easily measured in the majority of primary care and specialist practices.
Immune-mediated hemolytic anemia is a disease that often begins with a critical, potentially life-threatening crisis, producing symptoms that prompt a visit to the veterinarian. The anemia may be difficult to control, and hospitalization, possibly with intensive care, is necessary for several days in many cases. After this period, or else right away in milder cases, oral medications are started and given daily for several weeks to months. Immune-mediated hemolytic anemia is a disease that can respond very well to treatment (all symptoms are abolished and the animal enters a clinical remission) or that may produce recurrent problems despite treatment—this varies from one dog to another. With IMHA, there is always a risk of recurrence, such that affected dogs need to be followed closely with veterinary rechecks.
Cause: Anemia is a condition where the blood is too “thin,” as a result of a lower than normal number of red blood cells in the bloodstream. Red blood cells are important because they supply oxygen to all parts of the body, and when severe anemia is present, all of the body’s tissues are oxygen-starved, leading to symptoms such as sluggishness, loss of appetite, and even collapse and unconsciousness.
If your dog or cat is taking medication that might be triggering this disease, it must be discontinued. This needs to be discussed with your veterinarian first. If an infection is suspected, an appropriate medication is given to lessen or eradicate the infection. Intravenous fluids are often given to control dehydration. Corticosteroids (cortisone-like drugs, such as prednisone or dexamethasone) are commonly administered to subdue the excessively active immune system that is destroying the red blood cells. Other immunosuppressive drugs are often given in addition to corticosteroids for greater effect, and to eventually allow a more rapid reduction in dose of corticosteroid (NOTE: corticosteroids have many side effects, including increased thirst, urination, appetite, weight gain). Whole blood or red blood cell transfusions are sometimes necessary in moderate and severe cases to replace red blood cells that have been destroyed. Oxygen may be given. Because a serious complication of this disease is the formation of blood clots, blood thinners (anticoagulants) are likely to be given as well. Some of these anticoagulant drugs are given as pills, and others are given by injection.
Spherocytes are a type of deformed red blood cell that can be detected on a routine blood test in many dogs with IMHA but not in healthy dogs; the presence of spherocytes is strongly suggestive of IMHA. An autoagglutination test is performed to determine if red blood cells clump together, which is a positive indicator of this disease. The Coombs’ test reveals if certain molecules are present on the red blood cells’ surface. Other tests may be appropriate for your dog or cat, including tests to try to find a trigger for IMHA. Your veterinarian will discuss medical tests with you because this type of anemia requires them for confirmation.
Immune-mediated hemolytic anemia (IMHA) is a particular cause of anemia in which the number of red blood cells is low because they are destroyed (hemolyzed) by the body’s own immune system. In the healthy body, the immune system attacks foreign invaders such as bacteria and viruses. However, in immune-mediated hemolytic anemia, the body misidentifies normal healthy red blood cells as foreign and destroys them faster than the body can replace them. In some pets, the onset of this disease appears to be somehow connected to or triggered by severe generalized infections, medications, cancer, and other immune-mediated problems. However, if and how these events cause immune-mediated hemolytic anemia remains unknown, and in the majority of cases of immune-mediated hemolytic anemia, an actual trigger for the whole process is never found.
Anemia In Dogs: Immune Mediated Hemolytic Anemia
Cause: Anemia is a condition where the blood is too “thin,” as a result of a lower than normal number of red blood cells in the bloodstream. Red blood cells are important because they supply oxygen to all parts of the body, and when severe anemia is present, all of the body’s tissues are oxygen-starved, leading to symptoms such as sluggishness, loss of appetite, and even collapse and unconsciousness.
Immune-mediated hemolytic anemia (IMHA) is a particular cause of anemia in which the number of red blood cells is low because they are destroyed (hemolyzed) by the body’s own immune system. In the healthy body, the immune system attacks foreign invaders such as bacteria and viruses. However, in immune-mediated hemolytic anemia, the body misidentifies normal healthy red blood cells as foreign and destroys them faster than the body can replace them. In some pets, the onset of this disease appears to be somehow connected to or triggered by severe generalized infections, medications, cancer, and other immune-mediated problems. However, if and how these events cause immune-mediated hemolytic anemia remains unknown, and in the majority of cases of immune-mediated hemolytic anemia, an actual trigger for the whole process is never found.
This disease is diagnosed far more commonly in dogs than in cats. In dogs, it occurs more often in females. Cocker spaniels, poodles, springer spaniels, Old English sheepdogs, and Irish setters are affected more often than other breeds, although any dog, including mixed breeds, can develop this disease. Symptoms range from mild, vague symptoms to severe, life-threatening problems such as respiratory difficulty (see Signs to Watch For). Mild symptoms can quickly progress to severe, advanced disease, and a patient with these symptoms needs to be screened for anemia with a blood test performed by a veterinarian.
Diagnosis: Anemia (whether immune-mediated or not) can be suspected by a veterinarian when the oral mucous membranes (gums and tongue) are paler than normal. A definitive diagnosis of anemia comes from a standard blood test, which shows a lower than normal red blood cell count (hematocrit or packed cell volume are other measures of red blood cells). There are many causes of anemia in general, and the results of several tests as well as a complete history and thorough physical exam help to arrive at the diagnosis of immune-mediated hemolytic anemia. Be sure to share all information with your veterinarian regarding your dog’s or cat’s medical history, including the kinds of symptoms you have seen and how long they have been present, whether you have given your pet any medications in the preceding days, and so on.
Spherocytes are a type of deformed red blood cell that can be detected on a routine blood test in many dogs with IMHA but not in healthy dogs; the presence of spherocytes is strongly suggestive of IMHA. An autoagglutination test is performed to determine if red blood cells clump together, which is a positive indicator of this disease. The Coombs’ test reveals if certain molecules are present on the red blood cells’ surface. Other tests may be appropriate for your dog or cat, including tests to try to find a trigger for IMHA. Your veterinarian will discuss medical tests with you because this type of anemia requires them for confirmation.
During treatment, one or more of these exams may be repeated to help assess the effectiveness of treatment and to determine if adjustments are necessary. Subsequent test results may also make the long-term course of the disease clearer (help to arrive at an outlook, or prognosis).
Immune-mediated hemolytic anemia is a disease that often begins with a critical, potentially life-threatening crisis, producing symptoms that prompt a visit to the veterinarian. The anemia may be difficult to control, and hospitalization, possibly with intensive care, is necessary for several days in many cases. After this period, or else right away in milder cases, oral medications are started and given daily for several weeks to months. Immune-mediated hemolytic anemia is a disease that can respond very well to treatment (all symptoms are abolished and the animal enters a clinical remission) or that may produce recurrent problems despite treatment—this varies from one dog to another. With IMHA, there is always a risk of recurrence, such that affected dogs need to be followed closely with veterinary rechecks.
If your dog or cat is taking medication that might be triggering this disease, it must be discontinued. This needs to be discussed with your veterinarian first. If an infection is suspected, an appropriate medication is given to lessen or eradicate the infection. Intravenous fluids are often given to control dehydration. Corticosteroids (cortisone-like drugs, such as prednisone or dexamethasone) are commonly administered to subdue the excessively active immune system that is destroying the red blood cells. Other immunosuppressive drugs are often given in addition to corticosteroids for greater effect, and to eventually allow a more rapid reduction in dose of corticosteroid (NOTE: corticosteroids have many side effects, including increased thirst, urination, appetite, weight gain). Whole blood or red blood cell transfusions are sometimes necessary in moderate and severe cases to replace red blood cells that have been destroyed. Oxygen may be given. Because a serious complication of this disease is the formation of blood clots, blood thinners (anticoagulants) are likely to be given as well. Some of these anticoagulant drugs are given as pills, and others are given by injection.
Other treatment options are available, depending on how advanced the immune-mediated hemolytic anemia is. Not all of these treatments may be necessary for your dog or cat. Your veterinarian will tailor the treatment regimen for your pet. Immune-mediated hemolytic anemia is a life-threatening disease that can change and progress quickly. Although many affected dogs recover completely, they will require medications and frequent rechecks for months or even years. Sadly, many dogs with the disease succumb to the illness and die either in the first critical days after diagnosis, or are euthanized later on as a result of complications or relapse related to the disease or its treatment. There is a significant investment of effort and money in treating a dog with this disease. You should have a realistic conversation with your veterinarian about the outlook for your pet; it is not unreasonable to consider euthanasia (lethal injection to cause a painless death) either at the time of diagnosis, or if there is not a rapid response to treatment.