AIHA followed by IMTP

[tykesway]

Hi, I've recently joined the site but have been a regular 'broswer' for about the last 5 months since my 5yr old Cocker Spaniel (Skye) was diagnosed with AIHA. Luckily I'm a vet nurse so the signs were spotted early and she began the prednisolone treatment plan suggested by this website (along with gut and liver protectants). Before each drop in steroids Skye was blood tested and thankfully responded well and gradually her red blood cells increased to the point where everything had been within normal levels for the last 3 or 4 reductions in steroids. However, her blood test yesterday has shown that although everything is normal with the red cells, her platelet count (which has never been affected before) is worryingly down to 7! So it looks like Skye has now developed IMTP (despite not showing any outward signs yet) and we have to go right back to the beginning of the steroid protocol - which is frustrating as she was down to steroids every 3 days and was back to her usual 'crazy spaniel' self.
Just wondered if anyone on here had heard of or experienced anything similar ? At the minute Skye is bright, alert and energetic so I'm just grateful that we've been regularly blood testing her otherwise we might not have picked up on this new development til it was too late- and I'm praying that she responds as quickly as she did before to the high dose of steroids. I know relapses can occur but didn't realise the cell type affected could alter.
Sorry its such a long post....but any help/advice would be gratefully received. Thankyou.

[Jo CIMDA]

Hi Tykesqay

I'm so sorry Skye has IMTP but the good news is you know she responds well to the steroids.  As her plateltes are so low (I presume you have checked another sample and the accuracy of the machine) watch they don't go even lower because it will take a few days after treatment has started, before an increase is seen in the circulation.

Does Skye have any bruising or obvious bleeding?  If she doesn't then I hope this diagnosis is a mistake.  Bruising and bleeding will usually occur when the platelets are below 40 so one would expect you to see some outward sign.

Dogs with IMTP don't normally show signs of being unwell.  It is one of those AI disease that can creep up on the owner so you are indeed fortunate that you are regularly checking her blood.  There is a very detailed article (I hope) about IMTP in the files (if there isn't please let me know). 

Skye must be treated very gently because you can't afford for her to knock herself and risk a bleed, also if you exercise her too much she can have a bleed in the joints, so treat her with kid gloves (I'm sure you do already) until her platelets are 50+ at least.

Do consider using the drug Vincristine if you feel the plateletes need a rapid boost.  Usually only one dose is needed but obviously if she can get away without having to use it then that's fine too.

Dogs who get primary autoimmune disease are genetically predisposed and there is no way of knowing if they are just predisposed to one AI disease, or two or many others. Therefore it is not unusual for a dog who has already had one AI disease to get another.  It may be that Skye initially had Evans syndrome (AIHA and IMTP together) but because you are on the ball and treated it early perhaps you did so before the platelets became too low.

I know it might not feel like it but your professional knowledge will help Skye enormously.

Jo

[Jo CIMDA]

Primary AutoimmuneThrombocytopenia (AITP)
(Autoimmune Destruction of the Blood Platelets)
Note: Normal platelet reference range is approximately150-400.

About the Blood Platelets
Blood platelets start their life in the bone marrow and migrate to the circulation of the blood.  When an injury occurs and 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 in the circulation of the blood, 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. 
The term 'Immune mediated thrombocytopenia' (IMTP) is used when the disease is secondary to an identified, underlying cause.  IMTP can be induced by a bacterial infection such as leptospirosis, tick borne disease, vaccinations, poisoning, drugs, and some cancers, such as lymphoma or haemangiosarcoma. In these cases the identified, underlying cause has to be treated.  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
Chemicals
Poisonous substances
Drugs
Vaccines
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 safely 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, unbeknown to you, supposing your dog had met with a 'trigger factor' that 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 and targeted to 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.
NOTE: There are numerous different autoimmune diseases affecting various parts of the body. Thrombocytopenia is only one of them.
Information about Thrombocytopenia
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 even 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 that have appeared well but 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. To the best of my knowledge, Beardies are not one of the breeds that suffer from genetic bleeding disorders such as Von Willebrand's disease or haemophilia A; therefore, if a Beardie shows 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, immunosuppressive 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. Lower doses of steroids will not have the desired effect.
Clinical signs

The similarities between these two cases are the extensive bruising, and the fact that both dogs were not showing any obvious signs of serious illness ( which would be more likely if there is an underlying condition causing IMTP). 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. Misty had a nose bleed because her platelets were so low she was spontaneously bleeding (bleeding for no apparent reason). 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 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 (which may show as 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.

Note: Sophie had a haematoma which is quite rare in cases of primary autoimmune thrombocytopenia (AITP) but common in dogs with secondary thrombocytopenia (IMTP). The above points are to be used as guidelines only.

Diagnosis:

Diagnosis of AITP 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.

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

Twice as many females develop thrombocytopenia 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, can confirm thrombocytopenia; however, a positive result does not differentiate between primary and secondary causes of the disease.

AITP may 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.
Treatment
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).

EXAMPLE:

Reproduced with kind permission of Prof. M J Day:

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


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. 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. 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 one episode of the disease. The best chance for survival is early diagnosis and the correct treatment regime.
A dog's owner relies on their vet to make an accurate diagnosis and prescribe the correct treatment regime for their dog's condition. Sadly, this is not always the case and sometimes dogs die as a result.  Autoimmune disease is not seen on a daily basis at many general veterinary surgeries and sometimes, because of the vet's lack of experience in this area, it can prove difficult for them to obtain a correct diagnosis and some vets, even with a definitive diagnosis, will not have the knowledge, or sometimes the courage, to choose the correct treatment regime for a dog with an autoimmune disease. This is the most common concern of the many owners who contact me. Autoimmune diseases need to be responded to without delay, and therefore, time is of the essence. It is important to have a good, working relationship with your dog's vet, but some owners, who are very concerned about their dog's treatment (or lack of it) are so worried about upsetting the relationship with the vet that they fail to challenge either their diagnosis or treatment. Owners have said that sometimes they felt intimidated by their vet. We lost a dog in these circumstances and I know what it feels like. Don't make the same mistake that I did.  It's too late for our girl now but I still have regrets. If you are very concerned and not 'happy' with either your vet's diagnosis and or treatment, don't worry about your special relationship, trust your intuition and ask for a referral to a specialist, or at least go to another vet who has experience in the area that your dog needs. Sometimes switching vets within the same practice is all that it needed to get your dog on the road to recovery. This approach will shorten your dog's suffering and alleviate much of your stress!  It is not easy to question any professional – but they are only human and not always right!  If you have a good working relationship with your vet, it should not be jeopardised by you wanting the best for treatment for your dog; if it is, you should question the value of such a relationship. What is the point of retaining a good relationship with your vet when, if it all goes wrong, you will no longer have your dog? The best relationship you can have is when your vet listens to your concerns and works with you to bring about the best possible outcome for your dog; this is so important when you have a dog with an autoimmune disease. Such vets will always be your dog's best friend and 'worth their weight in gold'.
Finally, 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 your dog as natural as possible.
For further information about autoimmune disease, please contact:
Jo Tucker 
cimda@aslog.co.uk

[Penel CIMDA moderator]

Hi and welcome.
I'm sorry to hear that Skye's bloods have come back with this problem - Jo has (as always) given you all the info above.
It's great for Skye that you're a vet nurse, because you will a) be ultra aware for Skye and, b) will no doubt be even more aware of this sort of problem with other dogs.  Your vets will be learning from Skye too.
As Jo said, sometimes the machines get it wrong, so let's hope this might have happened.
Any kind of stress can bring on this type of reaction - when my Saffy had SLE, a friend's dog nipped her bum (not breaking the skin) but the stress of that encounter caused her to relapse.  Sometimes very hot or very cold weather can cause a relapse as well.  Fireworks, building works in the house etc.

The other thing I'm personally so pleased about is that because of this new forum, you were able to lurk for months before posting.  I know many members questioned this "open-ness" when we started the new forum, but we get absolutely loads of views - so the amount of dogs this must be helping is tremendous.

Sorry for rambling and my fingers are crossed that Skye has a good weekend.

[tykesway]

Thankyou for your valuable information this afternoon. It does help knowing that there are others out there who are willing to share their experiences and knowledge of auto-immune diseases. Having done a bit more research I am now suspicious that Skye has Evans syndrome where the IMTP follows on from the AIHA ( instead of both occurring at the same time which is what normally happens with Evan's).
In terms of her symptoms, she has none at present (other than some bruising and swelling around her neck where the blood sample was taken from) which makes me me all the more grateful that I test her blood regularly or this might have gone un-diagnosed til it was too late! And yes a repeat sample was sent to the lab to double check the results- as I know how unreliable haematology machines can be at counting platelets!!
It just feels so frustrating that Skye's anaemia had been responding so well for the last 5 months, with a light at the end of the tunnel, to then have the rug pulled out from under us. So its back to beginning of the steroid protocol and wrapping her in cotton wool!!
Oh well, thankfully Skye doesn't understand what all the fuss is about- so long as the receptionists at work keep feeding her gravy bones she's happy.
Again, thankyou for providing such an informative website and I'll keep you updated of Skye's progress.

[Penel CIMDA moderator]

She's a very lucky dog and couldn't be in better hands.
I've not heard of Evans behaving this way either, usually the two diseases strike at the same time. Very unusual I think.
I'll ask Barley's specialist if he's heard of that.

[tykesway]

Thanks....and if you manage to find anymore information that would be great.
Trying not to over react this evening as the first signs of petechial haemorrhages are starting to appear on Skye's abdomen and the bruising on her neck is beginning to intensify.
I think my brain is just starting to catch up on the events of the last few days and reality is kicking in.....I just hope the steroids do their job !!

[Penel CIMDA moderator]

They worked before, they should work again.  I think you've got in early this time because of your blood testing, but probably the destruction had already started iyswim.

[tykesway]

Just a quick update on Skye's progress.
Her follow up haematology this week showed her platelet count had increased to 129 - so the steroids seem to be working. Interestingly, her red cell count had droppped to slightly below normal; which makes me suspicious that Jo was correct in her earlier post that Skye had both conditions (AIHA and IMTP = Evans syndrome) from the start ! Looking back at her platelet count in sept 2012 it was 160 (the low side of normal ) but as soon as the steroid therapy was initiated for the anaemia her platelets shot up to around 300!
Thankfully Skye has remained bright (despite a massive bruise on her chest - don't know where from); although yesterday she was vomiting 'fur balls' on/off. I thought the feathering on her legs and abdomen had fallen out due to the steroids but I'm suspicious that because the fur is coming out so easily she is swallowing it as she grooms herself Has anyone else heard of this
The vomiting finally stopped around 2 am this morning and since then she's eaten small amounts and managed to keep her medication down. Fingers crossed thats the end of the vomiting - her weight has dropped from 8.3kg to 7.6kg in the 12 days since the steroid therapy was increased, so at the minute she looks pretty frail!

[Penel CIMDA moderator]

Sorry to hear she's not doing so well.  Does she wear a harness, could the bruising have come from that?

Barley's fur is falling out in chunks too, it tends to happen about 3 months after they are on the higher dose I've found in the past.

Is she on Ranitidine or something to protect her tummy? I'm sure she is knowing you but thought i'd better check as you mentioned vomiting.

[Catherine]

>>>>her red cell count had droppped to slightly below normal;<<<<

When is her next blood test? What dosage of steroids is she on? You may have to increase again and take the reduction slower.


>>>>the fur is coming out so easily she is swallowing it as she grooms herself Has anyone else heard of this <<<<

This happened with my AIHA dog. Not only did I have to groom her more often (gently because of thinning skin) but I hoovered....and hoovered....and hoovered because she would lick the floor looking for bits of food or anything!

Have you had Skye's thyroid tested recently? I know the fur coming out is due to her illness and the steroids but it can also come out with Hypothyroidism so best to rule that out.

[Penel CIMDA moderator]

I don't think theres any point doing a thyroid test while she's on high doses of steroid is there?  Skye's Mum is a vet nurse so I'm sure she can double check that.

[Jo CIMDA]

Thankfully Skye has remained bright (despite a massive bruise on her chest - don't know where from); although yesterday she was vomiting 'fur balls' on/off. I thought the feathering on her legs and abdomen had fallen out due to the steroids but I'm suspicious that because the fur is coming out so easily she is swallowing it as she grooms herself Has anyone else heard of this
The vomiting finally stopped around 2 am this morning and since then she's eaten small amounts and managed to keep her medication down. Fingers crossed thats the end of the vomiting - her weight has dropped from 8.3kg to 7.6kg in the 12 days since the steroid therapy was increased, so at the minute she looks pretty frail!

Does Skye normally 'groom' herself?  The fur will come out as a result of steroid use but I wonder if constant licking or grooming indicates stress.  This can be due to her feeling nauseous, and like when a dog eats grass to make itself sick, perhaps Skye is using her fur to do the same thing.  Omeprazole or Ranitidine would be a good idea if you think this is possible.

I hope Skye is feeling better.

Jo

[tykesway]

Thanks for all the suggestions. Skye's feeling a lot better after her day of vomiting fur balls last week.
I think the stress of not being allowed to be as active as she normally was (prior to the AIHA starting last september she was a grade 6 agility dog -  and I'd just started re-introducing her to training again during February until we then discovered the IMTP!) combined with full anal glands and fur that comes out easily all contributed the problem! So I'm trying to keep her mind occupied and putting treats inside her Kong etc.
With regard to her medications, she's been on Zantac and antepsin since her steroid dose was put back up to 1mg/kg/12hrs, so I don't think the overgrooming is related to nausea.....but we'll wait and see... I might need to change her onto omeprazole if it continues.
Fingers crossed that's the last we see of fur balls.

[shawkyelisabeth]

I have been following Skys progress, although i cannot add to penels and jos posts, i wish you very well and hope sky will improve soon.
Fingers and paws crossed
Elisabeth with Cecil and her late soulmate Stella