What is Evan’s syndrome?
Evan’s syndrome is a term that may be used when a pet has both immune-mediated hemolytic anemia (IMHA) and immune-mediated thrombocytopenia (ITP). Roughly 60% of dogs with IMHA will also develop ITP.
Anemia is a medical term for a low number of red blood cells in circulation. Red blood cells supply oxygen to the body through a molecule called hemoglobin.
Thrombocytopenia refers to a low number of thrombocytes, also known as platelets. Platelets are small cells that help the blood to clot by clumping together and forming plugs in damaged blood vessels.
Both red blood cells and platelets are produced by the bone marrow and released into circulation. Anemia and thrombocytopenia can occur if the cells are destroyed or used up (such as with hemorrhage or bleeding) faster than the bone marrow can produce them. These disorders can also occur due to primary bone marrow disorders, such as leukemia, or drugs that cause bone marrow suppression.
"With Evan’s syndrome, your pet’s immune system targets and destroys red blood cells
(a process called hemolysis) and platelets."
“Immune-mediated” or “autoimmune” describes a situation in which the body reacts against its own tissues. With Evan’s syndrome, your pet’s immune system targets and destroys red blood cells (a process called hemolysis) and platelets. The immune system makes antibodies that coat the surface of the cells, which causes the immune system to recognize them as foreign and destroy them.
What causes Evan’s syndrome?
In many cases, there is no obvious inciting cause for Evan’s syndrome, and it is called primary, or idiopathic. Evan’s syndrome is considered secondary if an underlying cause of immune system dysregulation can be identified.
Primary Evan’s syndrome is more common than secondary Evan’s syndrome in dogs, and certain dog breeds are more likely to develop Evan’s syndrome, such as Old English sheepdogs, cocker spaniels and poodles. In cats, both primary and secondary Evan’s syndrome are considered rare.
Causes of secondary Evan’s syndrome include:
- Infectious diseases, such as Rocky Mountain Spotted Fever, ehrlichiosis, babesiosis, and hemotropic mycoplasmosis, in which blood parasites directly target the blood cells (these parasites are often spread by ticks or other insects)
- Infectious diseases such as leptospirosis, heartworm disease, canine distemper virus, and canine infectious hepatitis in dogs; and feline leukemia virus, feline immunodeficiency virus, and feline infectious peritonitis in cats
- Systemic inflammatory conditions such as severe bacterial infections, pancreatitis, bee stings, or snake bite envenomation
- Other autoimmune diseases such as lupus
- Cancer
- Recent vaccination has been implicated as a potential cause, but no studies have been done that support the association
- Drug reaction
What are the symptoms of Evan’s syndrome?
Fig. 1: Dog with pale gums, indicating anemia.Evan’s syndrome shows symptoms of both IMHA and ITP. Many dogs have severe anemia, and their gums look pale instead of pink. They may be weak, lethargic, and can collapse due to lack of oxygen to the body tissues. Many pets have increased breathing and heart rates as the body tries to compensate by getting more oxygen into circulation.
As red blood cell destruction progresses, a product called bilirubin is released due to the breakdown of hemoglobin. Bilirubin is a yellow pigment, and it can turn the urine dark yellow or orange. The skin, gums and whites of the eyes can also appear yellow (jaundiced).
As the platelet count drops lower, spontaneous bruising can occur. Small clumps of bruises called petechiae or larger bruises called ecchymosis can be observed, particularly on hairless areas of skin like the belly, as well as the gums and whites of the eyes.
Fig. 2: Dog with petechiae (small clumps of bruises).Large internal bleeds are typically not found, though blood can be seen in the urine, stool, vomit, or nose bleeds. If bleeding is within the eye, blindness can occur; if bleeding is within the central nervous system, seizures or other neurologic dysfunction can occur; and if bleeding is within the lungs, breathing difficulty can be observed.
Non-specific signs can also occur, such as fever, vomiting, decreased appetite, enlarged lymph nodes, and enlarged liver and/or spleen.
How is Evan’s syndrome diagnosed?
Your veterinarian will perform a physical exam to look for the symptoms discussed above. Anemia and thrombocytopenia are diagnosed with a test called a complete blood count (CBC). This test measures the red and white blood cells, as well as the platelets. The cells will also be evaluated under the microscope to determine their size and shape.
In many cases of immune-mediated hemolytic anemia, there are also elevated reticulocytes: immature red blood cells made and released by bone marrow to compensate for the anemia. In early cases, though, reticulocytes can be normal.
In some cases, a pet’s red blood cells clump together abnormally, which may be visible under the microscope or on the side of the blood vial. To confirm this clumping, or in cases where clumping is not apparent, a Coombs test may be done to detect antibodies to red blood cells. If anemia and/or thrombocytopenia are detected, then additional testing can be done to look for an underlying cause (indicating secondary Evans syndrome).
Recommended additional laboratory testing may include a biochemical profile to evaluate organ function and electrolyte levels, a urinalysis to assess the urinary tract, and screening for infectious diseases. Your veterinarian can test for tick-borne diseases, including ehrlichiosis, babesiosis, heartworm disease, and leptospirosis, depending on disease prevalence in your geographical location.
Imaging such as X-rays of the chest and abdomen, as well as an abdominal ultrasound, can look for the presence of cancer.
How is Evan’s syndrome treated?
If no underlying cause is found and primary Evan’s syndrome is suspected, then treatment is based on suppressing the abnormal immune response. Immunosuppressive medications will be the mainstay of treatment.
Typically, prednisone (or prednisolone in cats) is the first-line treatment. If insufficient response is seen, then additional immunosuppressive medications can be considered, such as azathioprine and cyclosporine. Melatonin can be added as an adjunctive therapy for ITP, as there is some evidence it can help modulate the immune system. If there is any suspicion of bleeding from the gastrointestinal tract, then antacids and anti-ulcer medications should be given.
If the anemia is life-threatening, then a blood transfusion will be required. The transfused red blood cells can also be destroyed, but it buys time as the other treatments begin to work.
In IMHA, the red blood cells tend to clump together. Unfortunately, that can lead to thromboembolism, in which small blood clots obstruct blood vessels. For this reason, anticoagulant medications are often used, such as low-dose aspirin or plavix. Other treatment options may be available at referral centers.
In pets with secondary Evan’s syndrome, treatment will also be directed at the underlying cause. Antibiotics may be started while awaiting further diagnostics.
Is there anything else I need to know?
Patients with very low platelet counts are at risk of bleeding. They may need strict cage rest to avoid any sort of trauma. If treatment is successful and the red blood cell and platelet numbers return to normal, then a slow taper of the medications will be required. This tapering will likely take 4 to 6 months, with rechecks and dose adjustments every couple of weeks. Faster tapers are associated with higher rates of relapse.
Vaccinating pets who have experienced Evan’s syndrome or other autoimmune diseases may not be recommended due to a potential risk of causing a recurrence, but that decision will be based on a risk/benefit discussion with your veterinarian.
What is the prognosis for Evan’s syndrome?
The prognosis depends on the underlying cause and the pet’s general condition at the time of diagnosis. If the condition is treated quickly, and if clinical signs are not extreme, then the prognosis is good. Relapses are common, though. Some patients require life-long immunosuppressive medications. Secondary infections from immunosuppression and other side effects of these medications are possible (such as diabetes with prednisone).
In patients with secondary Evan’s syndrome, prognosis is more variable and depends on whether the underlying cause can be successfully treated.
