Evans syndrome: breaking down IMHA and ITP
Immune-mediated hemolytic anemia (IMHA) can occur due to primary (idiopathic) or secondary (virus, bacteria, parasite) causes. Approximately 60-75% of dogs develop primary idiopathic IMHA rather than secondary. In both primary and secondary IMHA the immune system destroys red blood cells prematurely, faster than the rate at which new ones can be produced. It is not known what triggers this inappropriate antibody production in primary IMHA but it is thought that antibodies may bind to two different red blood cells, which in turn, cause the cells to clump together.
Immune-mediated thrombocytopenia (ITP), also known as Evans syndrome and by the acronym IMP, occurs due to primary (idiopathic) or secondary (e.g. drug reaction, neoplasia) causes. While IMHA involves the destruction of red blood cells, in ITP there is increased destruction of platelets by the body's own immune system, at a rate faster than they are produced in the bone marrow.
Immune-mediated hemolytic anemia (IMHA)
IMHA can affect both dogs and cats, but typically middle-aged dogs are more susceptible. In dogs that have secondary IMHA due to disease, spayed females are more commonly affected. There is some evidence of genetic predisposition in Cocker Spaniels and Miniature Schnauzers. Roughly 60% of dogs with IMHA will also experience ITP (Evans Syndrome).
The pet typically presents with signs of anemia, including weakness/collapse, lethargy, dull/depressed mentation, pale/white mucous membranes, bounding pulses, heart murmur, and tachycardia. As large quantities of red blood cells are broken down, bilirubin is released into the blood stream, which may overwhelm the liver, causing some patients to become icteric.
The diagnosis of IMHA relies heavily on bloodwork. On a complete blood count (CBC) 95% of dogs will have spherocytes (small, spherical red blood cells). Agglutination of the red blood cells usually occurs. A CBC should always be submitted to an outside laboratory.
The Coombs' test, also known as a direct antiglobulin test (DAT), offers a more conclusive diagnosis for IMHA, as it detects antibodies that are attached to the red blood cells. A series of dilutions takes place until agglutination occurs.
The complications of IMHA are vast. These include thrombocytopenia, disseminated intravascular coagulation (DIC), thromboembolism, gastrointestinal ulceration, renal failure, and refractory anemia. Thrombocytopenia can occur because of ITP or because of platelet consumption. The exact physiology of why ITP occurs concurrently with IMHA is unknown.
Treatment first includes dealing with any initial problems caused by the anemia. This may include oxygen supplementation and/or red blood cell transfusion. There are valid concerns that transfusing a patient may worsen the IMHA, therefore patients should not be transfused until they have a packed cell volume (PCV) of 20-22%. If patients with a PCV greater than 22% are transfused there is an increased risk of thromboembolism.
Fluid therapy is important, and stabilization of patients is usually done through the use of crystalloids. Maintenance of tissue perfusion is equally important, even when it results in further lowering of the hematocrit. Fluids are also important in maintaining renal perfusion and helping to deal with the high levels of circulating bilirubin. Patients experiencing disseminated intravascular coagulation should receive fresh frozen plasma.
If the pet is experiencing primary IMHA, immunosuppressive drugs are given along with gastrointestinal protectants to prevent GI bleeding. Corticosteroids (prednisone, prednisolone) are the primary drugs used for helping to suppress the immune system. Response to corticosteroids is reflected by a rising hematocrit, adequate reticulocytes, reduced spherocytes, and reduced agglutination of the red blood cells.
Azathioprine is a purine (mimics DNA and RNA) analogue immunosuppressive drug that is commonly combined with prednisone therapy. Since it is commonly used with prednisone, its efficacy alone is unknown. Azathioprine is low-cost and well tolerated in dogs, making it an attractive choice as an additional line of defence.
In humans intravenous immunoglobulin (IVIG) is considered a first line treatment and is used in cases where prednisone doses are dangerously high or are ineffective. There are several studies showing evidence that IVIG competitively inhibits the binding of canine IgG making it effective for IMHA. Unfortunately due to expense, periodic limited availability, potential increased risk of thromboembolic disease, and the concern of a hypersensitivity reaction to the human product, it is usually not the first choice of treatment in animals.
Lastly, both cyclosporine (Atopica™) and danazol (Danocrine®) have been used to treat IMHA as secondary line medications. Cyclosporine is generally well tolerated in dogs, but rare gastrointestinal signs can occur as a side effect which resolve after the drug is discontinued. The efficacy of danazol is not supported by any published reports and is rarely used, perhaps because it can be hepatotoxic in dogs.
Immune-mediated thrombocytopenia
While not as common as IMHA, ITP occurs in dogs and less commonly in cats and is more common in middle-aged females.
Clinical signs include petechial hemorrhage, ecchymoses, melena, hematuria, retinal hemorrhage, and epistaxis. A worsening of the signs occurs in patients with severe thrombocytopenia (<10,000 platelets/µL).
A diagnosis is performed by obtaining a platelet count. While a low in-house platelet test may suggest ITP, it is best to send a CBC for a manual platelet count. A platelet count of less then 30,000 in addition to a low mean platelet volume (MPV) is highly suggestive of ITP.
The biggest complication of ITP is DIC. Coagulation times should be checked and patients should be monitored for signs of excessive bleeding, petechiae, and ecchymoses.
Treatment is similar to that of IMHA. While transfusing with red blood cells is done to prevent life-threatening anemia in IMHA patients, the transfusion of platelet rich plasma or whole blood is not as common. Unfortunately platelets are extremely fragile and, if transfused, the patient's immune system will often destroy new platelets within hours.
Patients with ITP are treated with corticosteroids (prednisone, prednisolone) and other adjunctive therapies may also be added (azathioprine, cyclophosphamide, danazol, cyclosporine). Vincristine may be added to the therapy because it interferes with some immune system effects on the platelets and also helps to mature megakaryocytes into functional platelets more quickly.
Nursing care
Upon initial presentation these patients may require oxygen supplementation. Blood transfusions may be needed and will require diligent monitoring for any signs of a blood transfusion reaction including urticaria, vomiting, collapse, fever, shaking, or panting.
Physical exams should occur minimally every eight hours and include a heart rate, pulse rate, respiratory rate and effort, mucous membrane colour, capillary refill time, rectal temperature, and neurological status. If there is any change from normal parameters, the veterinarian should be notified. Because patients are at risk for DIC it is important to look for early signs, which include excessive bleeding after venipuncture sticks and/or petechiae on the gums, pinna, or abdomen of the pet.
It is important that IMHA patients have their blood pressure monitored minimally every 8-12 hours. If the mean arterial pressure falls below 60 mmHg, the kidneys and other organs are not being appropriately perfused, putting the pet at risk of organ failure.
Ultimately the patient’s condition may change quickly depending on the progression of the disease. It is imperative that appropriate nursing care is provided to them to allow for the best prognosis.
This article is based on a presentation given at The Veterinary Emergency and Critical Care Society Conference in San Antonio, TX. CVT
