Immune Mediated Hemolytic Anemia in Dogs - Introduction
Immune Mediated Hemolytic Anemia, or IMHA, is an immune-mediated hematologic disorder in which body’s immune system attacks its own red blood cells.
It is one of the most common autoimmune disorder in dogs and cats that could have serious consequences on the health of your pet.
IMHA, if not controlled or treated in a timely manner, can lead to the formation of blood clots in canines, mostly in their lungs and brain.
The disease is mostly idiopathic in origin, i.e., occurs on its own due to the inability of your dog’s primary immune system to function properly.
But the disease can also occur due to certain triggers like infections, inflammations, neoplastic diseases, drugs and vaccines.
It is commonly detected in middle-aged female dogs and in some particular breeds like English springer spaniels, cocker spaniels, poodles, collies, and Irish setters.
In this article, we’ll discuss all about Immune Mediated Hemolytic Anemia in dogs – what it is, its signs, diagnosis, progression, and the line of treatment.
What is Immune Mediated Hemolytic Anemia or IMHA?
IMHA is an autoimmune disorder. In it, the body’s own red blood cells are mistakenly identified as foreign bodies and are attacked and destroyed.
Due to this targeted destruction, there’s a drastic reduction in the number of red blood cells in the body, which leads to anemia.
Some dogs with IMHA also experience reduction in the number of platelets.
Since platelets help in clot formation, a decline in their number leads to abnormal bleeding – a condition known as Immune Mediated Thrombocytopenia (ITP).
When both the conditions occur together, the disease is known as Evans syndrome.
What Causes IMHA in Dogs?
As mentioned above, IMHA can be both primary (idiopathic) and secondary.
In primary IMHA, the dog’s immune system stops working properly. It starts making antibodies that target its own blood cells.
This leads to the reduction of red blood cells in the dog’s body and a drop in oxygen delivery.
It is estimated that nearly three quarter of IMHA cases in dogs are primary in origin.
Secondary IMHA occurs when the surface of RBCs alters due to an underlying disease or toxin.
The triggers include cancer, infections like Ehrlichia or Leptospira, blood parasites like Babesia, snakebites, drug reactions, chemicals and toxins, or bee stings.
Sudden stressful events, at times, can also trigger secondary immune mediated hemolytic anemia in dogs.
Signs of Hemolytic Anemia in Dogs
The signs and symptoms of hemolytic anemia varies from one dog to another and often depends upon its underlying cause.
However, IMHA in dogs symptoms usually include:
· Pale gums
· Yellow eyes
· Lethargy and weakness
· Shallow or rapid breathing
· Lack of appetite
· High pulse rate
· Excessive weight loss
· Black/Tarry stools
· Dark orange or brown colored urine
· Dirt eating
Some less common signs of IMHA include:
· Sudden death
Diagnosis of Immune Mediated Hemolytic Anemia
If your dog is exhibiting any of the above mentioned symptoms, it is important to get him thoroughly checked by a veterinary doctor to detect the underlying cause.
He’ll evaluate his health to determine the disease and the root cause behind it.
If IMHA is detected, your veterinarian will recommend some diagnostic tests to understand whether the disease is primary or secondary. The tests may include:
Complete Blood Count
A blood test may be recommended to understand if your dog is anemic or not. If so, the test will help determine if his body is producing new red blood cells or not.
The test is performed to detect the number of reticulocytes or immature red blood cells present in the blood.
Also known as antiglobulin testing, Coombs test is an antibody test performed to detect the presence of RBC attacking antibodies in the body, which are known to induce hemolysis.
Serologic Blood Tests
Pathologic examination of blood to detect the presence of parasites in blood and associated diseases that might be leading to secondary hemolytic anemia in your dog.
A biochemical profile of your dog may also be ordered by your veterinarian to evaluate various organ functions, including kidney, liver, pancreatic function and your dog’s sugar levels.
To ensure your dog is not dehydrated or suffering from electrolyte imbalance.
A urine test may also be ordered by the doctor to screen your dog for various urinary tract infections or associated disease. The tests also help the doctor to evaluate your dog’s kidneys to concentrate urine.
Fecal tests help the doctor to evaluate the presence of intestinal parasites.
It helps to detect the presence of cancer in the lungs
An abdominal ultrasound examination helps your doctor to detect or exclude the presence of cancer in the abdomen.
Treating IMHA in Dogs
IMHA is a severe but treatable condition; however, aggressive care and timely detection of the disease is important.
Your veterinarian would determine if your dog needs hospitalization or could be treated as an outpatient.
The line of treatment varies according to the condition of the dog and the rate of disease progression.
Therapy consists of two phases:
· Acute phase
· Chronic maintenance phase
The line of treatment includes:
In this type of therapy, a variety of immunosuppressant drugs are administered into your pet’s body to kill the immune-suppressing lymphocyte cells.
Steroids are the mainstay of IMHA treatment.
Prednisone and dexamethasone are the two most popular steroid medicines used for the immuno-suppression therapy.
These hormones are toxic to lymphocytes and help in their removal from the blood stream.
The lymphocyte cells are the ones that produce antibodies, which are responsible for the lysis of healthy RBCs.
So, if lymphocytes are not present in the blood, there will be no antibodies to coat the red blood cells, and they will not be targeted for removal.
Steroids have various detrimental effects on your pet’s body.
These include excessive thirst, predisposition to urinary tract infection, thin skin, uneven distribution of fat around the body, panting and many more.
But in dog’s suffering from IMHA, steroid therapy is the only way around.
Also, the undesirable side effects of steroids diminish as the disease progression stops and the administration of steroids is withdrawn.
Additional Immune Suppression
Sometimes, even after the use of corticosteroids, a minimum amount of IMHA is seen.
In such cases, stronger immune suppressing agents are used as a part of therapy.
The most common medicines used in this case are azathioprine and cyclosporine A.
Prednisolone is another immunosuppressive drug of choice.
Other drugs that are used to suppress this autoimmune disorder include Mycophenolate mofetil, human immunoglobulins, and liposome-encapsulated clodronate.
The medicines offer similar benefits – to provide extra immune suppression to treat hemolytic anemia and to reduce the necessary dose of steroids.
Side effects associated with these medicines include vomiting, diarrhea, lethargy, loss of appetite, lymphopenia and susceptibility to secondary infections.
Blood transfusion usually acts as a last line of treatment in IMHA.
In this, well-matched whole blood or packed red cells are administered into the dog’s body every 3-4 weeks.
However, since even the newly transfused RBCs have the same chances of destruction as patient’s own red blood cells.
That’s why, several transfusions become necessary during the treatment.
Anti-thrombotic medications constitute to be an important part of IMHA therapy as thromboembolism is most common in hemolytic anemia.
To prevent venous clots from forming, unfractionated anti-coagulant medicines like heparin, clopidogrel, or aspirin are administered.
However, out of all, heparin has shown much better efficacy. The dosage of heparin is adjusted by the doctor after the measurement of anti-factor Xa levels.
Rivaroxaban is another anti-factor Xa inhibitor that is being used to prevent venous thrombosis.
However, the use of rivaroxaban in canine IMHA patients is not widespread.
Consult your vet on the best options available for this.
Therapeutic plasma exchange (TPE)
TPE, also known as Plasmapheresis, is the process of removal, treatment, and return of blood plasma back into the patient’s blood circulation.
It’s an extra corporeal therapy that helps in the rapid removal of autoantibodies from the plasma and can help cure acute or severe cases of IMHA.
In recent years, therapeutic plasma exchange has gained wide acceptance by veterinarians for the treatment for refractory or severe cases of immune mediated hemolytic anemia.
Splenectomy is a surgical procedure that’s used in refractory cases of canine IMHA.
It is recommended in dogs who fail to respond to immunosuppressive medicinal therapies.
It is also a line of treatment in dogs in which remission is achieved only when high doses of immunosuppressive agents are administered.
However, the treatment cannot be performed in dogs who are on multiple immunosuppressive medications.
In addition to this, before performing the surgery, the doctor has to ensure that the dog is stable.
He should also not be suffering from other infectious diseases.
A number of new therapies are also being developed for treating IMHA in dogs.
These include the development of monoclonal antibody therapy to re-induce self-tolerance in dogs suffering from IMHA.
The selective depletion of B cells, recombinant IL-2 therapy to induce regulatory T-cell production and transfusion of regulatory T-cells are some of the other therapies that are being developed.
In addition to all the above mentioned curative measures, various aggressive supportive therapies are also critical for dogs suffering from hemolytic anemia.
These include fluid therapy, oxygen therapy, the use of gastric protectants, plasmapheresis and splenectomy.
In this type of therapy, intravenous fluids are administered into the patient’s body in order to maintain the adequate volume of fluids and to prevent acid-base homeostasis.
Fluid therapy is highly beneficial in animals who are either dehydrated or are suffering from intravascular hemolysis and hemoglobinuria.
However, while performing fluid therapy, proper care must be taken to ensure that the administered fluid do not contribute to volume overload.
Oxygen therapy is highly beneficial in dogs with pulmonary diseases, especially in ones suffering from pulmonary thromboembolism.
In such dogs, whole blood or packed RBCs are administered to improve the oxygen levels in the body.
Oxygen support is advised by a veterinarian when your dog’s anemia is severe or when he’s suffering from other clinical issues.
These include tissue hypoxia, dyspnea, tachypnea, tachycardia, mental dullness, and weakness.
In many cases, gastric protectants are included as a part of IMHA therapy because the administration of glucocorticoids may result in gastrointestinal ulcers.
The gastric protectants used to prevent or cure gastrointestinal ulcers include omeprazole, sucralfate and famotidine.
Nursing and care
Good nursing and care is also of prime importance for dogs suffering from IMHA.
This includes daily intravenous catheter care, timely walks, good hygiene, proper nutrition, low-stress environment and limited phlebotomy for proper disease management and better health outcome.
Prognosis for IMHA
The prognosis of dogs suffering from IMHA depends upon the dog’s general health condition and the time of diagnosis of the disease.
Generally, the mortality rates in dogs with immune mediated hemolytic anemia is 26% to 70%.
The main reason of death in most of the IMHA cases is pulmonary thromboembolism, a blockage in the lungs that can lead to sudden death.
However, associated abnormalities may also lead to the dog’s death.
These include auto-agglutination, leukocytosis, thrombocytopenia, hyperbilirubinemia, and hypoalbuminemia.
But in majority of cases, the dog’s condition can be managed or improved through the use of appropriate immunosuppressive drugs, steroids, and supportive therapies.
Once the condition improves, your veterinarian will slowly and steadily taper off the immunosuppressive medicines to reduce the side effects of steroids and associated therapies.
However, even after your dog has been completely cured, you would have to monitor your dog’s health closely as relapses are quite common in IMHA.
Management of IMHA relapse
In case of a relapse, a decrease in the amount of RBCs happen again.
If it occurs, the cause for the IMHA relapse has to be investigated thoroughly by the doctor.
The veterinarian, prior to initiation of the treatment, needs to rule out other diseases like gastrointestinal hemorrhage or other infectious diseases.
He needs to restart the administration of immunosuppressive drugs and prednisolone.
However, if IMHA relapse occurs, tapering off medicines become difficult in most of the cases.
There is a good amount of chance that the dog might has to stay on a low maintenance dose throughout his life.
Autoimmune hemolytic anemia in dogs life expectancy
Generally, after a relapse, the prognosis is not good, with survival rates dipping under 50% in most cases.