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Your pet’s immune system provides the ability to resist and recover from disease and injury. This defense system regulates the production of antibodies that aid in destruction of disease agents, such as bacteria and viruses. In autoimmune hemolytic anemia, this defense system goes astray and attacks the animal’s own body and red blood cells (RBC), causing accelerated destruction or removal of red blood cells, which can lead to severe, life-threatening anemia. Sometimes the bone marrow cannot regenerate the red blood cells.

Causes

The key event initiating autoimmune disease is a breakdown in the control mechanisms that regulate lymphocyte components and activity of the immune system. Major research is still going on in this area, but much evidence points toward an infectious trigger in genetically susceptible animals.

AIHA may be a primary or secondary disease. In primary AIHA, no underlying cause can be identified, it is a true idiopathic disease.

In secondary AIHA, the RBC autoantibodies occur secondary to an underlying cause, particularly neoplasia (cancer), chronic inflammatory disease, certain drug reactions, or exposure to an infectious agent. In newborns, the disease may result from antibodies found in the first milk (colostrum) of the mother.

  • Infectious causes – Hemobartonella, Babesia, Leptospira, Ehrlichia, FeLV, other viruses
  • Exposure of previously unexposed antigens
  • Heartworm disease
  • Chronic inflammation – can occur concurrently with colitis
  • Neoplasia – Lymphoma, hemangiosarcoma, myeloproliferative disease
  • Drugs – sulfa drugs, cephalosporins, heparin, methimazole, quinidine, propylthiouracil
  • Type III hypersensitivity reactions – bee stings
  • Vaccination – An AIHA-vaccination link has been proposed, generally based on a temporal association (timing) between vaccination and disease onset (within a four week period). No statistically significant association has been proved. No particular vaccine has incriminated. Less than 4 in 10,000 dogs have been suspected of having this reaction to vaccines.

Signalment

This disease rarely happens in cats. Certain dog breeds are predisposed to this disease: Old English sheepdogs, Cocker spaniels, poodles, Irish setters, English springer spaniels, and collies. Trigger factors such as stress, estrus, whelping, and infection may affect these genetically susceptible dogs. AIHA occurs primarily in females with a mean age of 5-6 years (the reported range is 1-13 years).

Clinical signs

The clinical disease of AIHA can vary, depending on a combination of predisposing factors, including host immune and environmental influences. Anemia (low red blood cell count) resulting in pale mucous membranes is the primary clinical sign seen. Other clinical signs may include collapse, weakness, lethargy, anorexia (lack of appetite), exercise intolerance, dyspnea (difficulty breathing), tachypnea (rapid heart rate), vomiting, diarrhea, fever may or may not be present, jaundice (yellow mucus membranes), joint pain, petechia (bruising) and occasionally increased drinking and urinating.

Diagnosis

Based upon the clinical history and physical examination, several laboratory tests are indicated to confirm AIHA.

CBC (Complete Blood Cell Count) - The red blood cell count is low, often with a PCV (packed cell volume) of less than 20%. White blood cell count may be elevated, decreased, or normal. Platelets are often concurrently low. Blood smears often reveal abnormal red blood cells.

Serum Chemistry – These tests are used primarily to rule out other concurrent diseases. Elevated liver enzymes are common with AIHA.

Autoimmune Profile (Coomb’s, Antinuclear Antibody, and Rheumatoid Factor) – This is the diagnostic test of choice. Unfortunately, this test cannot be run in house and may take several days to get results. Please keep in mind that occasionally the Coomb’s test will be negative with AIHA.

Tick Panel (Ehrlichia, RMSF, Lyme) – This test may need to be done to rule out these diseases when thrombocytopenia (low platelet count) is present.

Radiographs/Ultrasound – These may need to be performed if the presence of a tumor is suspected.

Bone Marrow Biopsy – This test is indicated when the anemia is nonregenerative and there is little or poor response to treatment.

Treatment of AIHA is geared toward two specific areas:

Specific treatment to stop hemolysis (destruction of red blood cells)

High corticosteroid doses are the first choice for stopping red blood cell production. In the early course of treatment, the patient’s PCV (packed cell volume) is closely monitored to assure response to therapy. Once the PCV is above 30%, the steroid dose may gradually be tapered over the next 3-6 months. If the disease is in remission after 6 months and the pet is on a very low every other day dose of steroid, the steroid may then be discontinued. If AIHA relapses after drug withdrawal, corticosteroids need to be reinstituted. Patients with primary AIHA may need long term or lifelong treatment and relapses may be difficult to control in these patients. Side effects from corticosteroids include, but are not limited to, increased water consumption and urination, increased appetite, weight gain, stomach and/or intestinal ulceration and increased susceptibility to infections due to immune suppression.

If the patient does not respond to corticosteroids alone, other immunosuppressive drugs are then added to the treatment (Azathioprine, Cyclophosphamide, Cyclosporine, Danazol). Azathioprine is the drug most commonly used. Adverse effects from this drug include hepatopathy (liver disease), bone marrow suppression, pancreatitis and gastrointestinal upset. Patients on this medication will also need to be closely monitored (CBC and Serum Chemistry) during treatment.

Supportive care

Maintenance of tissue oxygenation is the goal of therapy for AIHA. Severe tissue hypoxia (low oxygen levels) can exacerbate AIHA complications such as DIC (disseminated intravascular coagulation) and thromboembolic (blood clot) disease.

Patients will need to receive either a whole blood transfusion or infusion of a synthetic hemoglobin solution (Oxyglobin). Although there is a risk of blood transfusion reaction, transfusions are usually not associated with marked increases in morbidity or mortality. Oxyglobin improves tissue oxygenation, but will not increase the packed cell volume.

Aggressive supportive care is critical to a good outcome in dogs with AIHA. Intravenous or subcutaneous fluids are usually needed to maintain proper hydration, ventilation and perfusion, and acid-base homeostasis. Gastrointestinal protectants may be necessary in some patients receiving ulcerogenic drugs (steroids). Patients with suspected DIC or thromboembolic disease are treated with heparin sodium and aspirin. Prognosis is guarded in patients with these clinical signs.

Prognosis

AIHA should always be considered a serious disease. Approximately one third to one half of affected dogs will die in the acute (early) phase of the disease, from early relapsing disease, or from the side effects of immunosuppressive therapy. In contrast, some dogs with chronic-onset AIHA may make an excellent recovery with appropriate supportive and immunosuppressive therapy; but, these dogs do remain at risk for relapse.

When AIHA is secondary to an underlying disease such as cancer or infection, the prognosis is more closely related to the underlying disorder than the anemia.

Recovered AIHA patients should be monitored closely the first six to twelve months, then throughout their lifetimes.

In Summary

  1. Autoimmune hemolytic anemia is a serious, life-threatening disease. In many cases, immediate blood transfusions are needed. Less severe cases are treated with a variety of medications. In some patients, surgical removal of the spleen or treatment with anti-cancer drugs is necessary.
  2. Various laboratory tests are necessary to diagnose the condition and monitor the response to treatment.
  3. Relapses are common.
  4. Medication must be given as directed. Call the doctor if you cannot give the medication.
  5. Diet: Follow the instructions checked.
  6. Activity: Follow the instructions checked.

Notify the Doctor if Any of the Following Occur:

  • Your pet’s signs recur after an apparent recovery.
  • Your pet seems short of breath or weak.
  • Your pet’s gums and tongue seem pale.
  • Your pet’s stool or urine are dark or blood-tinged.
  • Your pet has nosebleeds or hemorrhages of the gums, eyes, or skin.