Introductiion

[val]

Hi,
I am an owner of a whippet.  We went through a long recovery period with her, having autoimmune.  We do not know for sure, but there is suspicion oral tick meds may have been the start of the problem.  That was over a year ago. We thought we now could breathe a sigh of relief.  We do everything we can to make sure she is healthy, good foods, good supplements etc.  This past week, on a Sunday she began to cough.  During the night it got worse and I knew she was having a hard time.  We took her to the vet immediately when they opened on Monday morning.  Many test and xrays, nothing conclusive, except the best they could decide was bacterial pneumonia. She is on meds and steroids again, as they felt the platelet count was low.  We are beside ourselves.  The whippet means everything to us.. but we are scared.. is this a never ending cycle with her.. anyone have any thoughts, or anything as whippet owners you can tell us to help our worry and fear. Does it ever get better, or our we always looking over our shoulder for the next thing and the next ....  Thanks so much.

[Jo CIMDA]

Hi and welcome

I am sorry for the late reply.

Can you say what autoimmune disease your whippet was diagnosed with last year?   This may give a clue as to what is wrong with her now.

Some Whippets do have a genetic predisposition to autoimmune disease, and it is undetectable until it is triggered and they start to show symptoms.   There are numerous AI diseases but the majority are treated with immunosuppressive drugs such as prednsiolone.   Once the dog has been diagnosed with an AI disease there is always a chance that, after remission has been achieved, it may happen again, or a different AI disease is triggered.    This is not to say that with correct treatment long term remission can't be achieved - it can be and I have known hundreds of dogs to live a normal life after treatment.  Having said that is is also not unusual for dogs, especially when they are young, to relapse.

Bacterial pneumonia is not an AI disease, but it can be a secondary problem.  A low platelet count could indicate an AI disease called immune mediated thrombocytopenia (IMTP).  IMTP is treated with immunosuppressive doses of steroids or other immunosuppressive drugs.

So it can and does get better if the treatment is correct, and long term remission, and a long life, can be achieved.

I do hope you see improvement very soon.

Jo

[val]

Thank you so much for your reply.
She was diagnosed with Autoimmune hemolytic anemia.
She was on a fairly long course of predisone and other meds at that time.
This time they were unsure of ' the ' exact issue.. but xrays did show something in the lungs.  ( she was coughing-wheezing) And platelets low. They gave her an antibiotic along with a low dose, short term predisone.
My fear everyday is finding her down and out again...
I  feel our vets are new to the ' whippet- greyhound' breed..living in a rural area choices are limited and they have tried hard to help us.
Are there any tips, what should we do, look for.. what sort of daily regimen is best- health wise... medicine wise.. are there things as an owner I (we) can do, should be doing,  to prevent/ or lower the risk of issues.
Thank you so much.

[Jo CIMDA]

Hi

In the next couple of postings,  will post some information that might be useful to you.


Treatment for inflammatory/systemic Autoimmune Disease

Excluding autoimmune diseases where hormone replacement only is required, most of the diseases are treated by significantly suppressing the immune system in order to stop the destruction.  There are only a few exceptions to this.
The drugs most commonly used for the treatment of autoimmune/immune mediated disease are steroids (corticosteroids), such as prednisolone.  These may be used as the sole immunosuppressive agent or used in combination with cytotoxic drugs, such as Azathioprine. Cytotoxic drugs are used in human medicine to prevent the body rejecting transplanted organs. Many vets can be reluctant to use azathioprine with prednisolone as a combination therapy to treat autoimmune disease but there is certainly value in using a combined treatment as azathioprine increases immunosuppression and generally allows the steroids to be weaned down in the shortest possible time whilst maintaining a good level of immunosuppression.  It can make a huge difference to the outcome, and in some cases it makes remission more achievable.

All drugs have the potential to cause side effects and the major concern for treating animals with high doses of steroids and other potent drugs are the unacceptable side effects that may occur.  It is a fine balancing act between bringing the disease into remission and the side effects of the drugs.  All of the above drugs have the potential to cause a degree of liver toxicity but when the drugs are reduced the liver will recover. It has to be stated that without these life- saving drugs, in many cases, the dog would die, but the objective is to use the minimum dose to control the disease, for the minimum duration of time. However, the dose has to be 'immunosuppressive' eg.  Prednisolone 1-2mg/kg/every 12hrs usually starting at 1mg/kg/12hrs (Plumb's Veterinary Drug Handbook). If this dose does not produce the desired effect it can be raised. The action of prednisolone is rapid and at times it works like a 'miracle drug'.  Note: It should be given with food to minimise stomach irritation.

If the dose is too high the side effects may cause other major problems, if it is too low it will not control the disease or achieve remission.  One of the most common accounts are when a dog has been on immunosuppressive doses of prednisolone for too long and they start to display overwhelming signs of iatrogenic Cushing's syndrome (see below) and very often the clinical progress they have made in combating the disease has reached a plateau and the dog now appears to be weak, off their food and quite depressed. Prolonged, high doses of prednisolone can also cause bone marrow depression and the red blood cell count can decrease. These clinical signs can cause confusion for the vet and owner, and a relapse of the autoimmune disease is often suspected. It is not unusual for the steroids to be increased when in fact they should be decreased. 

Azathioprine is usually tolerated well, but as with all drugs individual dogs can be affected in different ways.  Side effects can include reduced bone marrow production, but this is rarely a problem unless the dog is kept on this drug for a long time. In contrast to prednisolone which has a rapid effect on the immune system, azathioprine takes at least 10 days to have some effect and approximately 4-6 weeks to reach its full potential. 

Note:  Azathioprine and all other cytotoxic drugs should be handled with extreme care. Cytotoxic drugs should not be handled by pregnant women.  Rubber gloves should be worn and the tablets should never be split or broken.

Atopica  (cyclosporine) is licensed for treatment of atopic dermatitis in the dog but it's increasingly being used as an immunosuppressant in 'combination' treatment with prednisolone and azathioprine for systemic autoimmune disease, despite the drug sheet stating   'It is not recommended to use other immunosuppressive agents concomitantly'.  I have known many dogs on this triple combination treatment that have eventually become overwhelmed by the side effects of the drugs and the outcome has been poor.  It may be worth, initially, trying a more simple approach to treatment, using immunosuppressive doses of prednisolone, before embarking on a 'prescription overkill' that may prove to be a difficult, and an unnecessarily heavy drug regime for the dog.   
The link below is an excellent resource:
https://www.dvm360.com/view/immunosuppressive-drugs-beyond-glucocorticoids-proceedings

It must be accepted that sometimes these 'heavy' drugs have to be used, especially if the dog is not responding to treatment; and sometimes an additional drug can make all the difference to the recovery of the dog. In these cases the side effects have to be accepted as a 'trade off', in fact the dog may tolerate it very well.  However, there may be no need to prescribe combination drugs when there is a good chance that using immunosuppressive doses of steroids, and following the correct drug regime, may be all that is required to bring the disease under control.  The severity of the disease has to be taken into consideration when deciding on which combination drug regime to use, but more isn't necessarily best, and introducing one combination drug at a time would limit the side effects for the dog.
In addition to drugs used to suppress the immune system, preventative measures such as administering antibiotics to prevent infection, gastroprotectants to avoid stomach ulcers, and low dose Aspirin to minimise the risk of thromboembolism and DIC (disseminated intravascular coagulation) may be given. 

WHAT TO EXPECT ONCE IMMUNOSUPPRESSIVE 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. Another gastroprotectant used is Omeprazole. 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, and 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 any time 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.

[Jo CIMDA]

Side Effects of the Drugs – Iatrogenic Cushing's Syndrome

Iatrogenic Cushing's syndrome is a side effect of high dose steroids and is caused by too much corticosteroid in the body. To a lesser extent, the immediate side effects observed when the dog initially goes on steroids eg., drinking, eating and urinating excessively is a mild example of Cushing's syndrome.  Personally I like to see dogs responding to high doses of prednisolone in this way, as it means that they are responding to the drugs as they should.
Usually, Cushing's syndrome only becomes a real problem when exceptionally high doses, or prolonged high doses of steroids are administered, maybe due to a relapse, or in some cases where the vet is inexperienced in reducing steroid doses and keeps the dog on a high dose for longer than necessary; or when the dog is not responding to treatment and higher doses are necessary to control the disease.  This is where the cytotoxic drug Azathioprine, and other more recently used, immunosuppressive drugs are very useful. 
All drugs carry side effects and Azathioprine is no exception, but it does not carry the same side effects as prednisolone, therefore by using this drug in combination with prednisolone it reduces the risk of iatrogenic Cushing's syndrome.  As Azathioprine takes at least 10 days to take effect, starting the 'combination' therapy at the beginning of treatment may enable the prednisolone to be lowered within the 10-28 day band and still maintain a good level of immunosuppression. If your dog is not responding to treatment then your vet may consider changing his treatment to other immunosuppressive drugs.

How Can I Tell if My Dog Develops Iatrogenic Cushing's Syndrome?
Iatrogenic means 'drug induced'.  Clinical signs of Iatrogenic Cushing's syndrome are the same as primary Cushing's syndrome but can present with acute clinical signs. It reflects the level of corticosteroid in the body.
The most notable side effects are, heavy panting, some hair loss, and an increase in drinking and urinating, excessive pigmentation.  This is something everyone seems to be aware of and accepts as normal when a dog is on high dose steroids. Very often the dog will be weaned down to a low dose before any major problems arise. 
Acute Cushing's syndrome due to overdosing of corticoid steroids can be very serious.  Blood results will reflect this, especially the liver enzymes which may be extremely high. Red blood cells and blood platelets may also be high and blood clotting may be a risk.
So when should you alert your vet to suspected, unacceptable level of corticosteroid?  The owner should take note when other clinical signs occur, such as: Depression, anorexia, muscle wasting and extreme weakness, continuous panting, lethargy - unwillingness to exercise, skin lesions and thinning of the skin, excessive hair loss, pot-bellied appearance and sagging back, behavioural changes (aggression).
If your dog is showing these signs it will probably mean that the dose of steroids needs to be lowered. It is important that it is not confused with a relapse of the dog's condition or an infection. The dilemma is that steroids must not be withdrawn too quickly otherwise the dog may go into an adrenal insufficiency crisis.  If the clinical signs of iatrogenic Cushing's syndrome is intolerable, it is hoped that the high dose of steroids that he has been on will have already done their job and that his autoimmune disease will be stable. As long as the steroids are lowered in a controlled manner and in time, all the symptoms of Cushing's will subside and your dog will return to normal, but extreme signs must not be ignored.

The Importance of Correct Treatment and Dosage
Iatrogenic Cushing's syndrome may also occur if the vet has initially prescribed a dose too high for the size of dog being treated.  For example:  I received an email from the owner of an Irish Setter, with AIHA.  The dog was prescribed 200mg of prednisolone each day. I called the owner, only to hear that the dog had to be put to sleep that day.  I was not surprised. The poor dog was on nearly twice the highest, recommended dose of prednisolone.  She was 9 years old and had never had a day's illness in her life.  What a terrible shock for the owners and what a lot of unnecessary suffering.  I know what it feels like because I too, have lost a dog due to prescribed overdosing of prednisolone.  The feelings of responsibility are enormous.
In contrast, some dogs are not treated with enough prednisolone.  Here's another story:
A greyhound diagnosed with immune mediated thrombocytopenia (IMTP).  Her vet gave her an initial shot of dexamethasone (a steroid which is 6 times stronger in terms of glucocorticoid activity than prednisolone).  Some vets choose to give a shot of 'Dex' as an initial therapy in autoimmune disease, especially if the patient is acutely ill.  Its effects can sometimes be seen within 6 hours and lasts for 36-72 hours.
The vet did really well and a marked improvement in her clinical signs was seen. It is usual, 24 to 48 hours after the shot of Dexamethasone for the treatment to change to an immunosuppressive dose of prednisolone tablets and for the owner to continue treatment in the usual way.  However, the vet only prescribed 5mg of prednisolone a day. The owner said they were very concerned that after a few days of improvement, she seemed to be very poorly again.  The vet couldn't understand why she was not continuing to improve.  He gave her another shot of Dexamethasone and the same improvement was seen.  I suggested to the owner that she either spoke to her vet about putting her dog on an immunosuppressive dose of prednisolone or change her vet.  They saw another vet in the practice, who was more experienced in treating autoimmune disease, and the dog was put on the correct, immunosuppressive dose of prednisolone and the treatment was successful.
These case histories demonstrate how important it is to treat promptly and correctly.

Reducing the Tablets
When significant improvement in the dog's condition is seen, usually between 10-28 days, the initial steroid dose is usually reduced by 25%. The dose is generally given for another 10 - 28 days and depending on the dog's progress and clinical signs the dose is significantly reduced once more for a further 10-28 days; and again in another 10-28 days. Anecdotal evidence has shown that if at this stage the dose is lowered more slowly, or reduced to an every other day dose over a period of months rather than weeks, relapse are less likely to occur.  It is always tempting to get your dog off steroids as soon as possible, but when treating autoimmune disease, as long as the dog is on a low, every other day dose then taking the last stage slowly seems to work best, depending, of course, on the severity of the disease and allowing for the difference in individual response - no two dogs reactions are exactly the same.  With some autoimmune diseases such as SLE, the dog is likely to be on steroids for the rest of his life. Usually an every other day dose can be achieved, but you risk a relapse if you take the dose too low. Below is the best example of a reducing immunosuppressive protocol I have come across. It is an excellent guide and can be adjusted to the individual.

Example: Reduction Protocol for prednisolone:

Clinical Immunology of the Dog & Cat , 2nd Edition,  by Michael J Day
Professor Michael DayBSc, BVMS(Hons), PhD, DSc, DiplECVP, FASM, FRCPath, FRCVS 

Professor of Veterinary Pathology, University of Bristol, UK and WSAVA - Chairman of Scientific Advisory Committee.
This example is based on a dog receiving an induction dose of 1.0mg/kg/q 12hrs (q = every)

Dose                           Duration (based on clinical effect)
1.0mg/kg/q 12h                          10-28 days
0.75mg/kg/q 12h                       10-28 days
0.5mg/kg/q 12h                         10-28 days
0.25mg/kg/q 12h                        10-28 days
0.25mg/kg/q 24h                        10-28 days
0.25-0.5mg/kg EOD                    at least 21 days
0.25-0.5 mg/kg every third day      at least 21 days

Every reduction is made after consideration to improvement of clinical signs, blood results and side effects of the drugs.

Prednisolone:  "Doses above 2.2mg/kg/day do not give more immunosuppression but do cause more side effects. Many internists believe that prednisolone doses should not exceed 80mg per day, regardless of the dog's weight."  Plumb's Veterinary Drug Handbook Eight Edition.

The dose of azathioprine 2mg/kg/24 or 48 hrs, can be reduced initially by giving a lower dose tablet per day, or gradually reducing from daily dosing to every 2nd day, every 3rd day, every 4th day etc.....  Remember, azathioprine tablets should not be broken or handled without gloves.

How Do I Know if My Dog Will Relapse?
Until you have attempted to wean your dog off of the tablets for the first time you will not know if he is likely to relapse or not.  Sometimes during the weaning off process, before you even get down to an every other day dose, he may relapse.  If this happens then the drug dosage has to be raised, probably up to the last dose before the relapse (maybe a little higher, depending on the severity of the relapse) and then start the weaning process again.  If this happens again, then you and your vet may have to settle for keeping him on a low maintenance dose to achieve a good quality of life. A low, every other day maintenance dose of prednisolone is preferred to enable the dog's liver to rest in between doses. There are many autoimmune diseases that carry a good, drug free prognosis.  The more common, serious autoimmune diseases that may not need long term steroid therapy are: primary immune-mediated polyarthritis, autoimmune haemolytic anaemia and thrombocytopenia. However, as previously stated, all dogs are different and it very much depends on the individual dog, the severity of the disease, the experience of the vet and the vigilance and compliance of its owner.
If a relapse occurs whilst the dog is still being treated then true remission has not been achieved.  If the dog has achieved remission and has enjoyed a period without drugs or is on EOD maintenance drugs, when a relapse occurs or he develops another autoimmune disease, he has encountered a 'trigger factor' which has induced this change.

[Jo CIMDA]

(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.  Immune mediated destruction of the red blood cells occurring within the circulation of the blood is known as regenerative immune mediated haemolytic anaemia.  This can be secondary to: tick borne diseases such as Lyme disease, cancer, haemangiosarcoma, parasites, poisoning (zinc, onions etc.), a reaction to drug administration, hyperthermia, systemic disease etc.
or
Primary non-regenerative AIHA (an autoimmune destruction of the immature red blood cells, or the precursor cells, within the bone marrow) where there is no detectible underlying disease.

Primary non-regenerative immune mediated haemolytic anaemia (NRIMHA) may also be termed as acquired Pure Red Cell Aplasia (PRCA).  It is thought that NRIMHA progresses to acquired PRCA and therefore the term PRCA is interchangeable.
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 blood cells or the precursor cells in the bone marrow, eventually the dog will become anaemic.  This is a chronic form of AHIA.

The destruction of the red blood 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 'Tell-tale' 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.  Your vet, however, may want to perform a bone marrow biopsy, but this is an intrusive procedure, especially in a very poorly dog, and is now considered a 'diagnostic overkill'.  A diagnosis of non-regenerative AIHA is often achieved by elimination of other primary or secondary causes of anaemia and, on examination of a blood smear, the absence of immature red blood cells.

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. An alternative to whole blood transfusion is intravenous human immunoglobulin (IVIG).  For more information see this link: http://veterinarymedicine.dvm360.com/just-ask-expert-human-igg-viable-treatment-imha  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.

(IMTP) Immune Mediated Thrombocytopenia

IMTP is a result of an immune destruction and decreased bone marrow production of the blood platelets.  Blood platelets are essential for blood clotting.   A dog with very low platelets can bleed to death in a relatively short period of time. The life of a blood platelet in a normal dog is approximately one week.  In a dog with IMTP the life of a platelet is no more than one day and may be only a few hours.

"Immune Mediated Thrombocytopenia (IMTP) is the most common cause of markedly decreased platelet count in the dog.  A strong presumptive diagnosis can be based solely on the detection of severe thrombocytopenia if history, physical examination and laboratory testing reveal no evidence of other causes. Treatment should therefore not be withheld in dogs with suspected IMTP pending results of specific anti-platelet antibody testing, particularly as such tests tend to be unreliable.  A presumptive diagnosis can usually be confirmed within 1-2 weeks by an appropriate response to immunosuppressive therapy".  Andrew Mackin, Chapter 36, Bleeding Disorders, Canine Medicine and Therapeutics by Neil Gorman [/b]

There is a very good reason for including the above reference as I have known many young dogs showing signs of bruising, and sometimes bleeding, and a low platelet count that have not been treated appropriately and have died.  If your breed is not known to suffer from a genetic bleeding disorder such as Von Willebrand's disease or haemophilia A, and is showing classic, clinical signs of IMTP and has a low platelet count, IMTP should be hastily considered and immunosuppressive treatment started without delay.
In addition to immunosuppressive doses of steroids, with or without Azathioprine, a single dose of the drug Vincristine can produce a dramatic rise in platelets and may be used in life threatening cases of IMTP.

Note:  Vincristine is on the list of drugs that is likely to cause an adverse reaction if the dog has MDR1 gene mutation. MDR1 is the multi-drug resistance gene that produces a protein called P-glycoprotein which prevents toxins from crossing the blood-brain-barrier. If this protein isn't present, because of a gene mutation, the body is unable to excrete the drug and toxins will build up within the brain resulting in neurological symptoms. A simple cheek swab or blood test will determine the dog's status for the MDR1 gene, and it might be prudent to consider this before using Vincristine. Collie breeds more likely to have a MDR1 deficiency but for a list of breeds known to have the MDR1 mutation please refer to:  http://www.ashgi.org/home-page/genetics-info/faq/mdr1-faqs

Recent studies suggest the addition of Melatonin to immunosuppressive treatment increases platelet count and is safe and effective in the treatment of refractory IMTP with little or no noticeable side effects.

If the platelet count is particularly low, it may be necessary to give a whole blood transfusion or a platelet rich transfusion to 'buy time' for the treatment to work. Of course other secondary causes of platelet destruction have to be taken into account and these include poisoning, bacterial infection, such as leptospirosis or, usually in older animals, cancer.

IMTP is more common in younger animals (this is another clue to aid a diagnosis).  You might see the first signs of bruising on the belly, chest or legs.  Evidence of blood in the urine and black tarry faeces (melena) indicates internal bleeding.  Your dog may vomit dark blood which looks like 'coffee grounds'.  Blood shot eyes and spontaneous bleeding, from both nostrils, gums, in fact any orifice, may occur when the platelets are less than 40,000 (normal range 150,000-400,000). However, for unknown reasons, not all dogs with very low platelets will bleed excessively.  Note: reference ranges may differ from one laboratory to another.  Clinical signs can include weakness and lethargy, pale gums, enlarged lymph nodes, high temperature and anorexia.  However it is not unusual for the dog to appear perfectly normal apart from external signs of bruising or bleeding.  The dog's apparent wellness belies this condition and owner or vet should not be lulled into a false sense of security because the dog is bright and eating well. Regenerative anaemia may be present due to bleeding.

Note: Platelet counts by an automated machine analyser should always be verified by examination of a blood smear.

Evans Syndrome

When both IMTP and AIHA occur concurrently, this is known as Evans syndrome.  The treatment protocol for Evans Syndrome is the same as IMTP or AIHA, but often the survival rate is lower. The dog has not one, but two, separate life threatening conditions to overcome.  However, I have known many dogs with Evans syndrome achieve remission and do very well.

[Jo CIMDA]

Hi

I hope the information is useful to you - although it might be a lot to take in. 

Basically, inflammatory AI diseases are treated by giving immunosuppressive drugs and the most commonly used and, also the most predictably effective, is prednsiolone.  If a relapse occurs then the dog has to be put back onto an immunosuppressive dose and treatment is started all over again - this is not uncommon.  The Prof. Michael J Day protocol is the best I have come across and it is effective in most cases, but it has to be tailored to the individual.

Greyhounds and other sight hounds can metabolise steroids differently and if the side effects are intolerable then another 'combination' immunosuppressive drug can be used and the dose of pred reduced.  When the dog has been weaned off the pred, all side effects will eventually disappear.

I suggest you have a read through the information and have a chat with your vet about where to go next.  If you have any problems, please get back to us here.

Good luck
Jo