Immune mediated hemolytic anemia

Immune Mediated Hemolytic Anemia (IMHA) or Autoimmune hemolytic anemia (AIHA)

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In hemolytic anemia, a loss of red blood cells (rbcs) occurs due to destruction of the rbcs. The destruction occurs due to antibodies which stick to the the rbc and cause the body to react, leading to destruction of the cell. This can be the direct result of a drug, toxin, blood parasite, virus or other primary cause or it can be an unexplained immune mediated reaction. It can occur inside the blood stream (intravascular hemolysis) or outside the bloodstream (extravascular hemolysis). In most cases in dogs, hemolysis occurs outside the blood stream in the spleen, liver and bone marrow. The destruction of red blood cells often leaves recognizable cellular debris in the blood stream. In particular, a form of damaged rbc known as a spherocyte occurs. Finding spherocytes on a blood smear almost guarantees that some form of hemolytic anemia is occurring. It does not really give a clue as to whether the IMHA is due to a primary cause or if it is occurring for no apparent reason, though. Since this disorder does not stop the production of red blood cells, there are usually immature red blood cells in the bloodstream which can be detected on the blood smears as well (a regenerative anemia).

The mechanism by which the immune system mistakes red blood cells for a "foreign invader" varies somewhat according to the cause. It usually involves adherence of the offending agent (parasite, drug, toxin, etc) to the surface of the rbc. The immune system wishes to attack this agent but manages to injure the rbc as well.

Dogs with IMHA usually experience a sudden onset of clinical signs, including depression, lethargy, pale gums or conjunctiva, sometimes jaundice or a heart murmur and bruising. Vomiting or abdominal pain may be present. It is unusual for overt blood loss to occur, such as nose bleeds or excessive bleeding from a minor injury. Death can occur rapidly, even with appropriate treatment.

Whenever hemolytic anemia is present it is wise to carefully rule out initiating causes that might be treatable. Examples of problems that can lead to hemolytic anemia include ehrlichiosis (a blood parasite), reactions to sulfa antiseptics or penicillin antibiotics, zinc toxicosis -- which can occur due to the ingestion of pennies. If any of these problems can be identified and treated the prognosis is much better.

The combination of clinical signs and spherocytes on a blood smear give a strong indication of this condition very rapidly. It can be confirmed using a Coomb`s test to check for antibodies adhered to red blood cells. This test is usually done at body temperature and at a colder temperature (4 degrees Celsius). A small percentage of dogs that have IMHA will not test positive on the Coomb`s test.

This condition will often respond well to very high doses of corticosteroids, such as prednisone. These medications suppress the immune system, allowing the rbcs to escape destruction. Improvement usually occurs within 1 to 3 days, if the dog is going to respond. If signs of icterus (jaundice) are present, the prognosis is usually worse. Dogs with this symptom may benefit from very aggressive treatment with anticoagulants and cyclophosphamide, a potent immune system inhibitor. Blood transfusions can be used in dogs with IMHA if necessary but they can make the condition worse so most vets reserve this approach for dogs that appear to be in imminent danger of dying due to severe anemia. It is necessary to treat most dogs for a fairly long time to prevent recurrence of the disease and some dogs seem to require lifelong use of corticosteroids or other immunosuppressants. Splenectomy is done in resistant cases since it is a major site of red blood cell destruction.

The Basenji, West Highland White terrier, English springer spaniel, Alaskan malamute, poodle and beagle breeds can be congenitally predisposed to this condition due to defects in enzymes (such as pyruvate kinase) or in the red blood cells.

Mike Richards, DVM

Video: Isabella's Story: Fighting IMHA

Immune mediated hemolytic anemia (IMHA) - Crisis Treatments

Question: Hello Dr. Mike

We wrote to you on February 25th about our Collie-mix female named Sprocket who started exhibiting abnormal signs when she started eating & vomiting dirt in early February. Her first PCV (on Feb. 10th) was 15, and she gradually dropped to 10 by Feb. 12th. A transfusion on Feb. 13 brought her to 25, which dropped gradually over ten days to 13. Initially, IMHA was not considered, but after no response to Procrit, she was given three tablets of Cyclophosphamide 50mg- and has been on Azathioprine- ¾ of a 50mg tablet every 48 hours. She started these last two drugs on Feb. 25th. Over that weekend, she started getting noticeably slower, and by the evening of Tuesday the 27th, she was very weak and her gums were nearly white. I took Sprocket to her doctor the next day (Feb. 28th), and her PCV was 7. She stayed for cross-matching and her second transfusion. She came home late afternoon.

Over the next few days she started losing her appetite, so we fed her bland human foods from an approved list the clinic gave us. She was VERY finicky with these too- liking some foods one day and not the next. She s had a RBC check every day since her transfusion: March 1: 25- March 2: 23, and this morning (March 5) it was down to 19. She has not been vomiting- she continues to drink excessively, due to the Prednisone. Her clinic suggested Imodium for the diarrhea, which has had just a tiny effect.

We visited Dr. B again this afternoon, and her outlook seems bleak. Sprocket has not responded to any of the medications. She has not even stabilized at any level. She is alive only because of the transfusions with help from Prednisone. The doctors only suggestion was to try another three-day trial of the Cyclophosphamide. If there is no response after that, (or perhaps a THIRD round of Cyclophosphamide), Dr. B said that we should consider putting Sprocket to sleep, or wait until her RBC is so low we are forced to put her to sleep. We are very sad.

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