Immune Mediated or Autoimmune THROMBOCYTOPENIA

Started by Jo CIMDA, July 29, 2014, 10:31:45 PM

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Primary AutoimmuneThrombocytopenia (AITP)
(Autoimmune Destruction of the Blood Platelets)

About the Blood Platelets
Blood platelets start their life in the bone marrow and migrate to the circulation of the blood.  When a blood vessel is damaged, blood loss is stemmed quickly by the formation of a blood clot or plug at the site of the injury. The plug is automatically formed by the circulating blood platelets.

Autoimmune or Immune Mediated Thrombocytopenia

Autoimmune or immune mediated thrombocytopenia is a result of an immune destruction and/or decreased bone marrow production of the blood platelets. If platelet numbers significantly decrease, the blood can lose its ability to clot and spontaneous bleeding can occur. It is likely that bleeding will be evident if the platelet numbers in the circulation fall below 40. However, not all dogs with very low platelets bleed excessively, and the reason for this is not known. 

Note: Normal platelet reference range is approximately150-400.

The term 'Immune mediated thrombocytopenia' (IMTP) is used when the disease is secondary to an underlying cause.  IMTP can be induced by a bacterial infection such as leptospirosis, vaccinations, poisoning, drugs, and some cancers, such as lymphoma or haemangiosarcoma. However, when a dog has thrombocytopenia and none of these associated causes are identified then it is most likely to be a primary autoimmune thrombocytopenia (AITP).  Although technically not correct, IMTP is often used to describe both autoimmune and immune mediated thrombocytopenia
AITP does not rely on a secondary cause, it occurs for apparently no reason, but only if the dog has a genetic predisposition to autoimmune disease.
Unfortunately, at this time, there are no tests to identify whether or not a dog is predisposed to autoimmune disease, so being aware of signs and symptoms is all the owner can do.
A dog with a genetic predisposition cannot develop an autoimmune disease without a 'trigger factor' (something that the dog encounters usually without causing ill effect, that triggers the immune system, causing it to react and malfunction). Trigger factors are numerous and very difficult to identify as they are often unknowingly encountered a while before the autoimmune disease becomes evident.

Known trigger factors are:

Stress:  eg., fireworks, thunderstorms, separation anxiety, whelping etc.
Hormones:  particularly if a bitch is in season, in whelp or nursing puppies.
Viral or bacterial infections
Poisonous substances

The Immune System and How Autoimmune Thrombocytopenia Occurs

The immune system is fundamental to life, and its function is to protect the body from foreign invaders, such as a viral or bacterial infection.  When the immune system detects for example, a bacteria (eg. when we have an infection) it mounts a response by producing antibodies that are targeted against the bacteria and engulf it and remove it from the body, making us well again.
A dog with an autoimmune disease does not have a weakened immune system, on the contrary it works extremely well - but what it does have is a confused one.  Returning to the trigger factor, supposing your dog had met with a 'trigger factor' which has caused the immune system to become confused, whereby it no longer recognises its own blood platelets as 'itself', eg. the immune system wrongly recognises the platelets as a foreign invader.
A response is mounted by the immune system (T and B cells) and auto-antibodies are released which destroy the blood platelets, causing thrombocytopenia.  This would only happen if the dog's genetic make-up allows it to, i.e. if the dog has a genetic predisposition to autoimmunity.
Because the immune system is designed to kill anything that may be harmful to the body, the destruction will continue until all the blood platelets have been destroyed, and the dog will die if not treated correctly and in time.   
So you can see that a dog with an autoimmune disease has a very powerful and efficient immune system, but unfortunately, because the immune system is malfunctioning and confused, it destroys parts of its own body. It's a case of mistaken identity!
NOTE: There are numerous different autoimmune diseases affecting various parts of the body. Thrombocytopenia is only one of them.

Information about Thrombocytopenia

As stated above, IMTP/AITP is a result of an immune destruction and decreased bone marrow production of the blood platelets.  As the 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 5 days.  In a dog with thrombocytopenia, the life of a platelet is no more than one day and may be only a few hours or less.
"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
There is a very good reason for including the above reference as I have known several young dogs showing signs of bruising, bleeding, and a low platelet count, that have not been treated appropriately and have died. This is usually because the vet cannot identify the reason for the dog's low platelet count and bruising etc., and is unsure of what to do or what treatment to give, but by not treating with immunosuppressive doses of steroids the dog's life is at risk. If your breed does not suffer from genetic bleeding disorders such as Von Willebrand's disease or haemophilia A;  and your dog is showing classic, clinical signs of thrombocytopenia and a low platelet count, and no other reasons for the low platelets can be identified, AITP should be hastily considered and correct treatment started without delay.  The treatment is designed to significantly suppress the immune system, in order to halt the destruction of the platelets, and allow platelet numbers in the circulation to increase.

Clinical signs

The dog's apparent wellness belies this serious condition and owner or vet should not be lulled into a false sense of security because the dog is bright and eating well. Any minor trauma can cause a bleed if the platelets are very low, even lifting or touching the dog can cause bruising.

You might see the first signs of bruising on the belly, under the arms, chest or legs.  Small pin-point bruising is very characteristic of AITP but areas of larger bruises and purple patches can also appear.  Your dog may vomit dark digested blood, which looks like 'coffee grounds',  and evidence of blood in the urine and/or black tarry faeces (melaena) indicates internal bleeding. Blood shot eyes and spontaneous bleeding from the nostrils, gums (in fact any orifice), can occur when the platelet count is low.  Bleeds within the central nervous system may cause neurological signs and a haemorrhage within the eye can cause sudden blindness. Regenerative anaemia may be present due to bleeding. If non-regenerative haemolytic anaemia is present with AITP then the dog may have Evan's Syndrome.

Some clinical signs that may aid a diagnosis and help to differentiate between primary autoimmune thrombocytopenia and secondary immune mediated thrombocytopenia

1. Autoimmune thrombocytopenia is more common in young to middle age dogs.

2. Small pin point bruises (known as petechiae or ecchymoses) and purple patches (purpura) are common in primary autoimmune thrombocytopenia (AITP) but are rare in secondary thrombocytopenia (IMTP) 

3. Secondary IMTP caused by, for example, rat poisoning would more likely show as larger areas of haemorrhage, such as body cavity haemorrhage,  haematomas (swelling containing blood), and bleeding into joints and muscles (may cause limping). 

4. A dog with AITP is likely to appear well. Fever, enlarged spleen, enlarged liver and lymph node involvement are more common in secondary IMTP and uncommon in primary AITP.

The above points are to be used as guidelines only.


Diagnosis is often presumptive and based on the absence of an underlying cause, blood test and smear results, which not only evaluate platelet numbers, platelet clumping and size (indicating the magnitude of thrombocytopenia) but can also exclude underlying causes, such as leptospirosis, heartworm and other parasites (especially important for dogs that have travelled abroad), recent drug use, cancer, and rat poisoning, which is usually on top of the vet's list of differential diagnoses. The dog's medical and travel history, and the appearance of clinical signs, age and breed of the dog should also be taken into consideration.

If secondary causes of thrombocytopenia are negative then a diagnosis of primary thrombocytopenia is often assumed.

Unless the evaluation of blood results suggests otherwise, a bone marrow biopsy is not routinely performed.

Twice as many females develop IMTP than males. The influence of hormones is considered to be a major trigger factor for AITP.

A blood test to check for anti-platelet antibodies, capable of binding to the blood platelets, confirms thrombocytopenia, however, a positive result does not differentiate between primary and secondary causes of the disease.

AITP can occur alongside other autoimmune diseases, such as autoimmune haemolytic anaemia (AIHA), known as Evan's syndrome, with rheumatoid arthritis, or with a multisystemic autoimmune disease, Systemic Lupus Erythematosus (SLE).
Note: Platelet counts by an automated machine analyser should always be verified by examination of a blood smear.


Keeping your dog as quiet and relaxed as possible, even cage rest, is very important to minimise trauma whilst there is a risk of haemorrhage.
Steroids are the main stay of treatment for most autoimmune diseases.  It is essential that they are given in immunosuppressive doses and for the correct duration of time (immunosuppressive dose of prednisolone: 1-2mg/kg/12hours, starting at the lowest dose, for a period of 10-28 days then the dose is reduced by 25% every 10-28 days until an every other day dose is achieved or the drugs stopped altogether. Clinical Immunology of the Dog and Cat by Michael J Day).
The treatment regime is absolutely crucial to the outcome.  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.  All dogs are different and some can tolerate the side effects of the drugs better than others. Small dogs seem more able to tolerate higher doses of steroids than larger dogs.
The vet may decide to use a combination therapy, using two drugs, for example prednisolone (a steroid) and Azathioprine.  A combination therapy minimises the side effects of the drugs and allows the steroids to be reduced whilst maintaining a good level of immunosuppression. Other, less commonly used drugs prescribed with prednisolone include: Cyclophosphamide, Cyclosporin and Danazole.  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.
A gastroprotectant should be given whilst a dog is on high doses of steroids to counteract the excess stomach acid produced by the steroids. Also, as a precaution, some vets will prescribe antibiotics when the immune system is significantly suppressed.
In addition to immunosuppressive doses of steroids, with or without the addition of a combination drug, 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:
If the platelet count is dangerously low, it may be necessary to give a whole blood transfusion or a platelet rich transfusion to 'buy time' for the treatment to work. The aim is to achieve remission. Some dogs are able to be weaned off of steroids altogether whilst others have to remain on a low every other day dose of steroids to control the disease.  When the dog is in remission it will be able to lead a normal, happy life. Some dogs can relapse but I have known many who have only had the one episode of the disease. The best chance for survival is early diagnosis and correct treatment regime.
If your dog has had an autoimmune disease (or even if it hasn't),  it is prudent to limit, as much as possible, any potential trigger factors and keep you dog as natural as possible.

For further information about autoimmune disease, please contact Jo Tucker:

All information is provided for assistance and reference purposes only and is not meant in any way to substitute advice or treatment from your veterinary surgeon.

Manual of Canine and Feline Haematology and Transfusion Medicine edited by Michael J Day, Andrew Mackin, Janet Littlewood.
Clinical Immunology of the Dog and Cat by Michael J Day.