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Author Topic: Auto Immune Haemolytic Anemia (AIHA) - start here.  (Read 11088 times)

Penel CIMDA moderator

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Auto Immune Haemolytic Anemia (AIHA) - start here.
« on: February 22, 2012, 02:39:43 PM »

(AIHA) Non-regenerative Autoimmune Haemolytic Anaemia 

A dog can be anaemic from either blood loss (internal bleeding), or destruction of the red blood cells, or a decrease in their production in the bone marrow. 

There are many reasons why anaemia might develop, eg. autoimmune (or immune mediated) destruction of the red blood cells occurring in the circulation of the blood (regenerative AIHA) or within the bone marrow (non-regenerative AIHA), tick borne diseases such as Lyme disease, cancers, parasites, poisoning (zinc, onions etc), a reaction to drug administration, hyperthermia, systemic disease. However, in the absence of an identified, underlying cause, the most common form of haemolytic anaemia is primary non-regenerative AIHA.

The life of a red blood cell is approximately 110-120 days. After this time the old red blood cells naturally leave the body and are replaced by young red blood cells, (reticulocytes).  Reticulocytes are formed in the bone marrow, and when they are ready they migrate to the circulation where they mature and then exit the body when their life span is complete.  It’s a circle of life – as the old red blood cells die off new ones replace them.  This is a normal daily occurrence.

If this normal process is prevented from happening, as in the case of a dog with non-regenerative AIHA, where the dog’s own immune system is producing antibodies which are destroying these young red cells in the bone marrow, eventually the dog will become anaemic.  This is a chronic form of AHIA.

The destruction of the red cells in the bone marrow starts some weeks before clinical signs appear and initially, the dog will cope quite well, as their body adjusts to the gradual effects of this form of anaemia.  However, eventually there will come a time when the lack of red blood cells in the circulation shows in various, external clinical signs.

Common, initial ‘telltale’ signs of chronic anaemia:
Your dog may have a craving to eat the earth or compost, or chew on concrete or bricks.  Another indicator could be bright orange coloured faeces and dark coloured urine (this is the blood pigment leaving the body). Your dog may become weak or lethargic, or even collapse for a few minutes through lack of oxygen to the brain, especially when excited. Take a look into your dog’s mouth and see if the gums appear pale. If the red blood cell count is extremely low, the tongue and whites of the eyes may have a blue tint to them. Occasionally the dog’s gums, skin and possibly whites of the eyes, will look yellow with jaundice. Other signs to consider include loss of appetite, high temperature, inexplicable limping and depression.  Consideration must be given to recent potential trigger factors such as hormone imbalance (recent season/whelping), vaccination, drugs, pesticides, flea treatments etc., also predisposing factors such as breed and age.

The family history of your dog is very relevant to any investigation, and can contribute towards achieving a diagnosis of an autoimmune disease. Dogs with a primary autoimmune disease have a genetic predisposition to one or several autoimmune diseases. Autoimmune disease runs in families so it is possible if one dog in a litter, or a relative, develops autoimmune disease the others may follow. 

Non-regenerative haemolytic anaemia is the most common form of primary AIHA but your vet should not assume this diagnosis. As stated previously, a dog can become anaemic for a variety of reasons and these will need to be investigated.  However, it appears some vets don’t consider that AIHA can be a primary disease occurring in the bone marrow and very often a grim, incorrect diagnosis of leukaemia is given.  Blood testing and examination of a blood smear is vitally important to a diagnosis of AIHA. A bone marrow biopsy, though very intrusive, may give a firm diagnosis but sometimes a diagnosis of non-regenerative AIHA is achieved by elimination of other primary or secondary causes of anaemia.

Autoimmune disease is often a ‘fight against time’.  If the red blood cells are below 12%, a blood transfusion is likely to be necessary to ‘buy time’ for the treatment to work.  The dog needs to be sustained through this early period of the disease. It is not necessary to have ‘typed’ donor blood for the first transfusion but subsequent transfusions need to be compatible therefore the recipients blood should be taken and sent away for blood typing before the first transfusion is given so that the type can be determined should another transfusion be necessary. Obviously, blood transfusions carry risks but they can also save lives. Early diagnosis and treatment may avoid this procedure. 

Once treatment has started, an increase in red blood cells will hopefully be seen in approximately 5 days (the time it takes for the reticulocytes to develop and migrate to the circulation). The level of reticulocytes seen in a normal blood smear is very low. When a dog is recovering from AIHA the levels should be very high and this reflects the level of anaemia.  Correct dosage and duration of treatment is absolutely crucial to a favourable outcome.

Immunosuppressive Protocols for Oral Prednisolone in the Dog.
Ref: Clinical Immunology of the Dog & Cat by Michael J Day  – Professor of Veterinary Pathology, University of Bristol, UK and WSAVA - Chairman of Scientific Advisory Committee.

This example is base on a dog receiving an induction dose of 1.0mg/kg/q12hrs

Dose                Duration (based on clinical effect)

1.0mg/kg/q12h             10-28 days
0.75mg/kg/q12h            10-28 days
0.5mg/kg/q12h             10-28 days
0.25mg/kg/q12h                         10-28 days
0.25mg/kg/q24h                         10-28 days
0.25-0.5mg/kg/ Every other day      at least 21 days
0.25-0.5 mg/kg/ Every third day       at least 21 days

Azathioprine (a cytotoxic drug) can be used in combination with prednisolone at 2mg/kg/24 or 48 hrs and dose gradually reduced, when remission is achieved, over a period of months.
Clinical response to Azathioprine may take up to 6 weeks. (Plumb’s Veterinary Drug Handbook)

Don't forget the gastroprotectant!


WHAT TO EXPECT ONCE TREATMENT HAS STARTED

If a dog has a serious autoimmune disease, then the sooner treatment commences the better chance the dog has of survival.  The main delay to starting treatment is obtaining a diagnosis or at least your vet being sure that he hasn’t missed anything that could be made worse by giving high doses of steroids.  Achieving a diagnosis can be a fight against time. 

If your vet has decided that in all probabilities your dog has an autoimmune disease, then to a certain extent, which autoimmune disease your dog has, as far as treatment is concerned, is irrelevant because with the exception of a few diseases, they are all treated the same, that is, with immunosuppressive drugs.  The main objective is to ‘knock out’ the immune system and virtually stop it from working (or near enough) so the destruction will cease and give the body a chance to recover.  As previously stated, this treatment regime works in most cases, that is, if it has been given early enough and the dosage is correct.  All dogs are different and some can tolerate the drugs better than others. In proportion to their size, small dogs seem more able to tolerate higher doses of steroids than large ones. Some diseases are more serious than others and carry a poorer prognosis. So the initial crisis is a crucial time, however anecdotal evidence shows that many more dogs survive than die if correct treatment is administered in good time.

It is hoped that a positive response can be seen within 4-6 hours of starting treatment (depending on the disease), but in a serious, life threatening situation, the first 2-7-14 days can be a very worrying time.  Assuming the dog has stabilised he will quickly feel much better, and if he is in hospital may be allowed home within a week.

When he comes home he will probably have a ‘goody bag’ full of drugs.  He will be on a high dose of steroid, usually prednisolone, and he may also be on another immunosuppressive drug, such as Azathioprine.  Your dog will be weaned off in a controlled manner according to his wellness and clinical observations. 

Note: High doses of steroids must not be stopped abruptly.  Your dog could go into an adrenal crisis if the medication is withdrawn too quickly. 

In addition to immunosuppressive drugs he should have something to protect his stomach from excess acid.  The last thing your dog needs when he is feeling poorly is a bleeding stomach ulcer caused by the drugs.  Sometimes, Antepsin is given to coat and protect the stomach (but this must not be given within two hours of other medication otherwise it will stop the drugs from being absorbed).  Zantac (Ranitidine) may also be prescribed to take away the excess acid. Zantac does not inhibit the absorption of the drugs. Another gastroprotectant used is omeprazol. To minimise irritation to the stomach it is usual for the daily dose of steroid to be split into two doses and given with food, one dose in the morning with breakfast and the other dose with his evening meal. I have known several dogs, who did not receive a gastroprotectant as a part of their treatment regime, who went on to develop anaemia. This is not autoimmune haemolytic anaemia but iron deficiency anaemia caused by bleeding stomach ulcers. Using a gastroprotectant is a good preventative measure. When the steroids have been significantly reduced to a low dose, a gastroprotectant may not be necessary.

Excess acid produced because of the drugs may make a dog prone to developing pancreatitis. A dog with pancreatitis will appear in pain and his back may be arched as if he can’t straighten up.  He may be lethargic, seem bloated and have a tender abdomen. Dogs usually go off food and water, may vomit and look depressed.  If you suspect that your dog has pancreatitis, don’t try to feed him because it will make the condition worse. Take him to the vet as soon as possible as he may require treatment or need to go on an intravenous drip to stop him dehydrating.  Again, the risk of pancreatitis should be minimal once the dog is on a lower dose of steroids.   A low fat diet is best when your dog is on high dose steroids or prone to pancreatitis. 

As your dog‘s immune system is being significantly suppressed, he will be more likely to pick up infections, and will not have the ability to fight against them.  As a precaution a broad spectrum antibiotic is often prescribed. Also it is sensible not to exercise him in areas where he is more likely to encounter infections, for example, a park or a popular dog walking area. 

Whilst your dog is on high dose steroids he will want to eat and drink excessively. However, this also means that he will want to urinate more and this can sometimes cause temporary incontinence.  You may have to get up to let him out during the night and if you leave the garden door open during the day, it may save some mopping up!  He cannot help it and won’t like it either, so don’t be too hard on him, it’s only temporary. You will notice as he is weaned off the drugs the unwanted side effects will subside and he should return to normal habits and behaviour.  Urinary tract infections and/or bacterial skin pustules are not uncommon when a dog’s immune system is suppressed, and this is often the reason for a dog to be off colour during this time.  Note: Always consider a urine infection if your dog seems under par.  A course of antibiotics will usually sort this out quickly.

Depending on what autoimmune disease your dog has, he will probably need to have regular blood tests.  Biochemical blood tests will also keep an eye on other body functions, such as those of the liver and kidneys, which is important at this stage.

Assuming good progress is being made, the clinical signs of his illness are diminishing and positive signs of improvement are apparent, your vet will want to start weaning him down from the high doses of steroid.  This process can take 3-6 months or more, and usually begins anytime after 10 - 28 days from the start of treatment, depending on the results of his blood tests and his clinical signs.
Relapses are not uncommon, especially in diseases that are difficult to control, for example SLE.  A relapse may mean that initially, your dog needed to be on a higher dose of immunosuppressive drugs for a longer period of time, or your dog may have been weaned off a little too quickly and then the dose withdrawn too soon.

If a relapse occurs he will probably show similar clinical signs to his initial crisis.  He will have to go back on an immunosuppressive dose of prednisolone, but it may not have to be quite as high as before. A combination drug may need to be added at this stage. The weaning process will then have to start all over again. Returning to an immunosuppressive dose will mean that he has to go back on a gastroprotectant.
« Last Edit: April 04, 2012, 06:08:47 PM by Jo CIMDA »
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Penel
(SLE, Surrey - UK)
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