IMHA

[KarenR]

Our 4 ½ year old Springer Spaniel, Robbie, has been diagnosed with IMHA.  It began back at the end of November, when he started to be particularly fussy with his food. On checking him over on 30 November I noticed his gums were pale and made an appointment at our vets that evening, where he was confirmed to be anaemic.  I can't remember the level of his PCV test but I think it was around 20. Between 30 November and 6th December he underwent various tests, a coombes test, urine and faeces analyses, a scan of his abdomen as well as blood tests.  All came back negative for any disease, by this time his PCB had dropped further and he was sent to a referral vets on 7 December for a bone marrow analysis, aspirate and a more detailed scan.  As his PCV had dropped to 15, it was decided to give him a blood transfusion to bide some time whilst we awaited the bone marrow results.  This transfusion increased his PCV to 25 and it stayed in the early 20s for the next 3 weeks. The bone marrow results showed his capacity to make new red blood cells but these could not be seen in the circulating blood stream, although where they are being killed off is still not known. His scan came back clear. At this point we did not have a diagnosis and the vets were uncertain if he was losing blood (although the couldn't detect where) or if this was an IMHA We started him on omaprazole after his first transfusion.

A blood test on 27th December revealed his PCV had dropped to 11 and he was admitted for a further transfusion and also stared on prednisolone 25mg twice a day.  The transfusion increased his PCV to 18 but two days later it was back down to 11.  He started on Mycophenolate on 30th December and was booked in for a third transfusion on Jan 1st. This increased his PCV to 21 but by today Jan 3rd this has dropped to 16.5.

We are starting to feel desperate as that third transfusion had been given as a "final treatment", the thinking being that this would give him the extra boost to get his meds to start working.  Our vets are willing to give a fourth transfusion but are also talking to us about having to make that difficult decision.

The vets (and he's now seen quite a few) all say he's not typical and they've not seen a dog not respond to treatment, but believe this could be a particularly aggressive form of the disease.

Thank you for taking the time to read, if you have any suggestions or advice we would be most grateful.

[Jo CIMDA]

Hi and welcome

I am sorry Robbie is not responding to treatment.  I have just a few questions, if you don't mind.

I presume Robbie weighs around 25kg, so he is now on an immunosuppressive dose of prednisolone (recommended starting dose prednisolone is 1mg/kg/12hrs).  Do you know if Robbie was producing new red blood cells prior to the transfusions, in other words has Robbie always had regenerative anaemia or was the initial diagnosis non-regenerative IMHA and he then developed something like a gastric ulcer which caused regenerative anaemia, as a result of blood loss, and not an immune destruction of the red blood cells?

As Robbie doesn't seem to be holding on to his new red blood cells, and if absolutely necessary your vet is prepared to give another transfusion, then perhaps they should consider a transfusion of intravenous human immunoglobulin (IVIG) as opposed to a whole canine blood transfusion. It has been successful in dogs that are not responding to immunosuppressive treatment.   I have known a transfusion of IVIG to make all the difference to the outcome of IMHA and IMTP (thrombocytopenia) and although there are no guarantees it is worth a try. 

This clinician's brief is by Michael J Day, Langford Vet School, Bristol.  Prof Day is among the world's top veterinary immunologists.

http://www.cliniciansbrief.com/sites/default/files/attachments/Canine%20Immune-Mediated%20Hemolytic%20Anemia_0.pdf

IV Human Immunoglobulin
 For refractory cases, administration of high
doses of human Ig blocks Fc receptors on
macrophages and inhibits extravascular
hemolysis

More links to information about IVIG transfusions:

http://veterinarymedicine.dvm360.com/just-ask-expert-human-igg-viable-treatment-imha

https://www.researchgate.net/publication/13761046_Intravenous_human_immunoglobulin_for_the_treatment_of_immune-mediated_hemolytic_anemia_in_13_dogs

If Robbie only started immunosuppressive doses of prednisolone on 27th December, then he hasn't been on it for very long.  The addition of mycophenolate might make a difference.

If Robbie has always had regenerative anaemia then it is often secondary to something else going on in the body and this will have to be discovered and treated as well as the IMHA.  Have they exhausted all the probabilities?

I don't know what referral vets you are seeing but have you thought about going to one of the vet colleges?  Many of the vet colleges have state of the art equipment, Critical Care departments, and professors in internal medicine on hand.  Depending on where you are in the country (I presume you are in the UK) The Royal Vet College in Hertfordshire, Cambridge Vet School, Bristol Vet School and Glasgow Vet School come highly recommended.

I do hope you see a turn around for Robbie very soon.

Jo

[KarenR]

Hi

Thanks for your reply.

Robbie weighs 21.5kg

I've checked back through his notes from our referral vets (Vale Vets in Gloucestershire) and they state it's non regenerative.  The bone marrow sampling found him to have regenerative capacity.  The initial diagnosis was either immune mediated destruction of the red blood cells or gastrointestinal blood loss.  I think that due to the lack of any evidence of gastrointestinal blood loss, the immune mediated haemolytic anaemia was diagnosed.

I can't help but feel that we are missing something.

[Catherine]

Perhaps the blood transfusions have affected the speed at which the immunosuppressive dose of Preds. would have started working to increase the PCV.

When is his next blood test? I would have another blood test for Robbie tomorrow (5th) and also have a full biochemistry one (checks ALKP, Ca, etc. and electrolytes) as well to check out how all his levels are doing not just the blood ones. Are his platelets okay?

[Jo CIMDA]

Hi

Thanks for your reply.

Robbie weighs 21.5kg

I've checked back through his notes from our referral vets (Vale Vets in Gloucestershire) and they state it's non regenerative.  The bone marrow sampling found him to have regenerative capacity.  The initial diagnosis was either immune mediated destruction of the red blood cells or gastrointestinal blood loss.  I think that due to the lack of any evidence of gastrointestinal blood loss, the immune mediated haemolytic anaemia was diagnosed.

I can't help but feel that we are missing something.

Hi

Non-regenerative AIHA is, not exclusively, but most likely to be primary, therefore no underlying cause. Coombs test is usually negative.

Just for a while, put to one side the thoughts of there being an underlying cause and consider this to be a destruction of the immature red blood cells within the bone marrow (NRAIHA) or a destruction of the red cell precursors within the bone marrow (PRCA).  This non-regenerative form of anaemia is the type most commonly seen when it is a true, idiopathic autoimmune disease.  In a way, the treatment is more straight forward because there is no primary cause such as a tumour, parasitic infection or poisoning to be dealt with.

The treatment is with immunosuppressive doses of steroids, with or without a 'combination' immunosuppressive drug such as Azathioprine, mycophenolate etc....  Thankfully Robbie is now receiving correct treatment.

It takes a minimum of 5-7 days for new red blood cells to migrate from the bone marrow to the circulation of the blood after starting immunosuppressive treatment with prednisolone.  Robbie has been on an immunosuppressive dose of prednisolone for just over one week so it is a bit early to be sure that he isn't responding to treatment.  They have said that his bone marrow has the capacity to regenerate, which is excellent news, so it needs more time.  This form of IMHA can, and does, usually respond to immunosuppressive treatment but  the response time varies in individuals and it may take weeks before for the haematological response is seen. During this time the dog can be supported by transfusions.

Many pedigree dogs, and increasingly cross breeds, have a genetic predisposition to autoimmunity and unfortunately, Springer's are no exception.  Something probably 6-8 weeks before you noticed the pale gums triggered this immune response. 

I am hopeful that when you next have blood taken you will see an increase in the HCT or at least the HCT stabilised and not reduced.

The IVIG is still a good option if his HCT goes below 12, but fingers crossed, he won't need it.

Jo

   

[KarenR]

His PCV test today shows his red blood cell count to be 15. Which, whilst not great, is not as bad as we feared so we feel a little more hopeful. 

The vets are considering putting him on an additional immunosupressant  - I can't remember the specific name, but I think it began with A.  At the moment i feel this would be my preferred option as i have that slight regret that not starting medication before Christmas was a mistake so don't want to risk leaving it too long again.

His booster vaccinations fell within that 6-8 week period prior to noticing the pale gums 

He is seeming quite spritely these last few days, showing interest in going out for a walk, and was delighted to great all the vets and nurses at the clinic today.  Fingers crossed he is turning a corner.

[Catherine]

My AIHA dog had Azathioprine as well as the Preds and had no problems with it. It will take a few weeks to kick in though. Another "A" is Atopica which I have had no experience of but there have been reports of dogs having sickness whilst taking that.

Although he seems well he still needs to take things slowly and should only go for a very short slow walk and preferably not in public areas because he is more prone to infection at the moment.

Hopefully the next test will show an increase although probably only a little.

[Jo CIMDA]

Hi
I am glad Robbie is spritely, that is a good sign, but like Catherine says, please take him gently just in case he can't cope with the exercise.  Sometimes when the HCT is low and they get excited they can collapse due to lack of enough red blood cells taking oxygen to the brain.  They are fine after a while but you and he can do without it.

I would think the other drug they are considering is Atopica (Cyclosporin). I only say this because it has a quicker onset of action than Azathioprine. 

I would take him back on Monday if you can to check that the HCT hasn't dropped further.

The vaccination 6-8 weeks ago has to be the trigger for this anaemia.  In future no more vaccinations, spot on treatments etc.  They are all potential triggers for AI disease and a dog who has been vaccinated as an adult doesn't need the core vaccines anyway because it is likely it will be immune to the core diseases that are vaccinated against  for life. The other non-core vaccines are unnecessary anyway for most pet dogs. Have a read  of the vaccination guidelines by the World Small Animal Veterinary Association.

  http://www.wsava.org/guidelines/vaccination-guidelines

Whether to vaccinate again, or use unnecessary drugs and preventative treatments, should be based on a risk/benefit assessment and the risk to a dog who has a genetic predisposition to autoimmunity most definitely outweighs the benefits. 

I do hope Robbie's HCT has increased next time.

Jo

[KarenR]

Thanks for your replies Jo and Catherine.  Don't worry we've not been taking him out for walks - its just nice to see that he is keen to go.  He's just got to potter round the garden for now!

You're correct that the new drug is Atopica.  He seems to be coping with it ok and we've not had any sickness.

Had another PCV test on Monday which showed his red cell count to be 16% so we're feeling a little more hopeful that maybe he can beat this. (I've changed the subject heading of this post as hopefully he is now responding to treatment!)

That's very interesting about the future vaccinations and spot on treatments.  He is overdue his Advocate but we thought best to hold off anyway whilst he has so much else to deal with. Are there alternative treatments for fleas and worms which would be ok? Not concerned for now, but thinking ahead.

[Jo CIMDA]

Hi

16% is good because he is holding his own.  Fingers crossed this is the turning point.

Best to use essential oils as a preventative tick and flea treatment.  Billy No Mates is just one product you can buy, but if you want to make your own use 15 drops in total of essential oils such as lavender, eucalyptus, clary sage, rose geranium, to 500mls of water  and you can use this as a grooming spray.  It is a repellent only, but it worked for my dogs. 

The genetic predisposition to autoimmunity will always be there  so limiting the triggers is the best thing you can do to prevent a relapse. 

I hope you have even better news soon.

Jo

[KarenR]

Unfortunately Robbie has deteriorated.  His PCV was up to 17% on Friday last week.  On Sunday morning we found him limping awkwardly on his back leg. Thinking he might have strained it we gave it a couple of days to see how he recovered.  We took him to the vets on Wednesday as it had not improved and also to check his PCV levels.  The vet found his knee joint was swollen and has prescribed tramadol for pain relief.  But most upsetting was that his PCV had dropped to 11%.  The vet has asked up to consider whether we wish to continue the treatment

He seems really depressed and struggling.  I'm just not sure what to do for the best.

[Jo CIMDA]

Hi Karen

I realise the situation you are in, and this is very understandable, but even with a PCV of 11% there is still a chance of turning this around.  I notice your vet in in Gloucester so rather than give up do you think Robbie would be able to make it to Birmingham, which is roughly an hour away from your area?  There is an excellent referral centre in Birmingham called The Willows.    https://www.willows.uk.net/  I have known many dogs to be successfully treated by the Willows and although there are no guarantees it is worth a try if you can afford it.

Ultimately you have to be happy with your decision but this could be a good option.  If you do decide to get a referral to the Willows then it needs to be now.

All the best
Jo

[KarenR]

Hi Jo
Our vets is actually in Worcester. Quite early on in this process, we were referred.  We had a choice between Willows in Birmingham and Vale Vets in Dursley, Gloucestershire.  We went with Vale as they could see him that same week, as opposed to waiting a week to go to Willows.   

What treatment would you anticipate a referral at this stage might involve?  Having spent in excess of £4000 already we are cautious of spending more when there are no guarantees.

[Jo CIMDA]

Hi Karen

Can you remind me again what medication Robbie is having?  Is he still on 25mg x 2 prednisolone a day, mycophenolate and atopica? 
A gastroprotectant?

A transfusion of IVIG would really be worth considering instead of another whole blood transfusion or packed cell transfusion.

https://www.researchgate.net/publication/13761046_Intravenous_human_immunoglobulin_for_the_treatment_of_immune-mediated_hemolytic_anemia_in_13_dogs

Jo