What is Evans Syndrome in Dogs?
Evans Syndrome in dogs is a severe and life-threatening autoimmune condition. Evans Syndrome is a complex disease where the immune system attacks and destroys a dog’s red blood cells and platelets.
It combines two autoimmune diseases, Immune-Mediated Hemolytic Anemia (IMHA) and Immune-Mediated Thrombocytopenia (IMTP). Any dog can be affected by Evans Syndrome, but middle-aged dogs are at an increased risk. Evans Syndrome is extremely rare in cats.
What is the Cause of Evans Syndrome in Dogs?
An abnormal immune response causes Evans Syndrome. This is where the dog’s body targets its own red blood cells and platelets for destruction.
The immune system consists of pro-inflammatory and anti-inflammatory chemical triggers. It also has the capacity to recognize its own cells. An autoimmune disease occurs when these mechanisms are compromised.
In an auto-immune condition, the full force of the immune system attacks the body’s own cells. In Evans Syndrome, this is directed at the body’s red blood cells and platelets. This causes rupture of the red blood cells and platelets.
An abnormal immune response can be primary or secondary. Most dogs with Evans Syndrome fall under the category of primary.
What is the Difference Between Primary and Secondary Evans Disease?
Primary Evans Syndrome has no known cause. This is also known as idiopathic. It means that the immune system has no identifiable trigger to attack the body’s own red blood cells or platelets. Primary Evans Syndrome is the most common.
Secondary Evans Syndrome occurs when the body receives a trigger before the auto-immune response. This is suspected when a patient has recently developed a new infection, started a new medication, or received a vaccination.
Primary and secondary Evans Syndrome are treated similarly. However, the trigger for secondary Evans Syndrome should always be investigated.
Clinical Signs of Evans Syndrome in Dogs
Clinical signs of Evans Syndrome can be severely life-threatening. Therefore, it is essential to look for symptoms of IMHA and IMTP as they can present differently.
Clinical signs of IMHA reflect the decreased red blood cells and decreased oxygen delivery to tissues.
- Decreased/absent appetite
- Exercise intolerance
- Pale mucous membranes
- Yellow mucous membranes
- Increased respiratory rate and effort
Clinical signs of IMTP reflect the lack of platelets in the body.
- Petechiae/ecchymoses – red-purple marks on the mucous membranes or skin
- Epistaxis – nose bleeds
- Haematochezia – blood in the stool
- Haematuria – blood in the urine
Dogs affected by Evans Syndrome can also present with signs of multi-organ damage as there is a lack of oxygen supply to vital tissues. Thromboemboli (blood clots) can also develop in the blood vessels supplying various organs. This is particularly important if affecting the lungs, liver, and kidneys.
- Increased heart rate
- Increased or decreased temperature
- Increased respiratory rate
Diagnosing Evans Syndrome in Canines
Diagnosis of Evans Syndrome is based on physical examination findings and blood work results. Routine blood work will show anemia and thrombocytopenia if both IMHA and IMTP are present.
In cases of IMHA, the anemia is strongly regenerative, which suggests that the bone marrow is producing new red blood cells. This is to try and combat the rapid destruction of mature red blood cells. Nucleated red blood cells (immature red cells) and polychromasia (red cells with varying densities) reflect regeneration.
White blood cell counts are usually also elevated due to immune system stimulation. Patients can also have elevated organ enzymes due to the stress from lack of oxygen.
A positive auto-agglutination test (where red blood cells clump together when mixed with saline) is supportive of IMHA. A blood smear will also show many round cells that are abnormally rounded (spherocytes).
A Coombs test, also known as a direct antiglobulin test, offers a more conclusive diagnosis for IMHA. This detects antibodies that are attached to the red blood cells.
In cases with IMTP, blood work results will show thrombocytopenia. This is confirmed by a blood smear in which low levels of platelets are seen. Typically, a combination of physical exam findings and blood work results will allow the veterinarian to diagnose Evans Syndrome.
Further diagnostics are required to diagnose an underlying inciting cause. This may include radiographs, ultrasound, advanced imaging, arthrocentesis, and others. In addition, as cancer can trigger an aberrant immune response, bone marrow analysis may also be recommended. However, as mentioned, the underlying cause is not always found.
Unpacking Immune-Mediated Hemolytic Anemia
As mentioned, IMHA is the destruction of red blood cells by the body’s own immune system. This results in anemia or a decreased red blood cell mass. Oxygenation to tissues around the body is thus compromised.
IMHA is the most common form of hemolytic anemia in dogs. Middle-aged dogs are more susceptible to IMHA than any other signalment. In dogs that have secondary IMHA, spayed females are more commonly affected.
Dogs with IMHA present with typical signs of anemia. This includes weakness/collapse, lethargy, depression, pale mucous membranes, bounding pulses, heart murmur, and tachycardia.
As large amounts of red blood cells are broken down, bilirubin is released into the bloodstream. This can overwhelm the liver and cause some patients to be icteric (yellow).
Diagnosis of IMHA relies heavily on blood work. Regenerative anemia, agglutination of red blood cells, and spherocytes are supportive of IMHA.
IMHA can have a variety of complications. This includes:
- Disseminated intravascular coagulation (DIC)
- Gastrointestinal ulceration
- Renal failure
- Refractory anemia
Roughly 60% of dogs with IMHA will also experience IMTP.
Discussing Immune-Mediated Thrombocytopenia
IMTP is not as common as IMHA, but the underlying principles are the same. IMTP is an auto-immune disease in which the body’s immune system attacks and destroys platelets. This results in a decreased ability to clot and can result in internal bleeding.
Clinical signs include petechial bleeding, ecchymoses, melena, haematuria, retinal hemorrhage, and epistaxis. A worsening of the signs occurs in patients with severe thrombocytopenia (< 10,000 platelets /uL).
IMTP is diagnosed by performing a platelet count. While a low in-house platelet count can suggest IMTP, sending a CBC for a manual count is best. A platelet count of less than 30,000/uL in addition to a low mean platelet volume is highly suggestive of IMTP.
A severe complication of IMTP is disseminated intravascular coagulation (DIC). DIC can lead to systemic inflammatory response syndrome (SIRS) and multi-organ dysfunction/failure (MODs). Therefore, it is vital to check for coagulation times, and patients should be monitored for signs of excessive bleeding.
Available Treatments in Combating Evans Syndrome
Treatment includes supportive care to stabilize the patient. This is prior to further treatment for Evans syndrome. Supportive care can include:
- Oxygen supplementation.
- Fluid therapy to maintain tissue perfusion, renal perfusion, and manage bilirubin levels.
- Transfusion of packed red blood cells, fresh frozen plasma, whole blood, or platelet-rich plasma.
Care should be taken when transfusing patients as it may worsen the IMHA. Patients should not be transfused unless they have a packed cell volume (PCV) less than 20-22%. Patients with a PCV higher than 22% are at an increased risk of thromboembolism.
Transfusion of platelet-rich plasma or whole blood for IMTP is not common. This is because platelets are incredibly fragile, and if transfused, the patient’s immune system will often destroy them.
Plasma exchange, or plasmapheresis, is a newer therapy available to treat severe cases of immune-mediated disease. Therapeutic plasma exchange involves exchanging the plasma component of the patient’s blood with that of a healthy plasma donor.
The patient’s blood is circulated through a filter to clean the patient’s plasma off the destructive circulating immune chemicals. This helps to preserve as many red blood cells and platelets as possible. As some of the patient’s plasma is removed during the process, a donor’s plasma must be returned to the patient.
Evans Syndrome is treated with medication to suppress the immune system from attacking its own cells. This is typically done with immunomodulating drugs. It is not uncommon for more than one immunomodulatory medication to be necessary to gain control of the disease.
Corticosteroids are the primary drugs used for suppressing 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 an immunosuppressive drug that is commonly combined with corticosteroid therapy. Azathioprine is well tolerated in dogs and cost-effective. This makes it a first-line choice for supplemental treatment.
Cyclosporine and danazol can be used as secondary line medications. Cyclosporine is well tolerated in dogs. It can have gastrointestinal signs as side effects. Danazol is rarely used as it can cause hepatotoxicity.
Vincristine may be added as an additional therapy. It is used in IMTP as it can interfere with the immune system’s effects on platelets. It also helps to mature megakaryocytes into functional platelets more quickly.
In cases of secondary Evans Syndrome due to infection, antibiotics will be required to treat the condition. Secondary Evans Syndrome can also be caused by cancer. The cancer may be treated with chemotherapy, radiation, or other disease-directed therapy.
What Will Long Term Follow-up Entail?
Patients with Evans Syndrome will require long-term medication to suppress their immune system. Close monitoring in the early phase of the disease is critical. Discontinuing medication too soon can result in a relapse of inflammation. Unfortunately, relapses can be more severe than the initial onset of the disease.
Follow-ups include regular checkups and blood work to monitor the progression of treatment. It also tracks any possible side effects of the medication.
The goal of treatment is to reduce the medication to the lowest effective dose eventually. However, this may take months to achieve long-term control.
What is the Prognosis of Canines With Evans Syndrome?
Evans Syndrome is a life-threatening disease. It is more severe than IMHA or IMTP on their own. Patients that require transfusions in the first few days of therapy will likely require several days of hospitalization.
The first few days of Evans Syndrome are critical as some patients do not respond to aggressive therapy. A patient that survives the first few days of treatment and is discharged home generally has a good long-term prognosis.
Close monitoring is always required, even when sent home.
Patients with secondary Evans Syndrome will have a variable prognosis. This depends on the inciting cause, as an infection will have a different prognosis to cancer.
The Survival Rate of Evans Syndrome in Dogs
Evans Syndrome is a life-threatening disease, and high mortality rates are seen in the first two to three weeks of treatment. Patients who do not respond to immunotherapy are unlikely to survive.
However, up to 80% of dogs diagnosed recover well enough to be released from the hospital. All patients diagnosed with Evans syndrome will require a lifetime of drug therapy.
Evans Syndrome is a severe auto-immune condition. Therefore, any clinical signs suggestive of IMHA or IMTP should be brought to a veterinarian’s attention as soon as possible. Diagnosis of Evans Syndrome is straightforward, and treatment is based on immune modulation.
The first few days after diagnosing Evans Syndrome are critical as patients can develop DIC, SIRS, or MODs. Lack of response to treatment carries a grave prognosis.