Not responding to pred

[tildesaz]

Hi all
You've been so helpful in the past. After an initial diagnosis of IMTP in Feb 2018 our spaniel has had 3 or 4 relapses since. She had been steroid free since June 2020 but last Monday became lethargic and had pale gums. PCV was 15. She was started back on 40mg pred in 2 lots of 4 tablets a day and an omeprazole. She was doing pretty well in herself normal RR and HR of 80. PCV was rechecked Friday and had dropped to 12. She is now having all 8 tablets in one go but she's still not improving and if anything RR and HR is worse. they've ordered her another med but couldn't get it til tomorrow. She's never had omeprazole before so could this be stopping her response to the pred or is she just over it now after so many relapses? She's only 7 and I'm so upset this could be the end but I don't want to prolong her pain if that's all I'm doing. Thanks for any advice

[Catherine]

So your spaniel has AIHA this time, is that correct? I assume the platelets are okay this time. How much does  she weigh? She needs to be on the correct dose.

It will take some days for the new red blood cells so she may need a blood transfusion to buy her some time. I have not heard about Omeprazole affecting the steroids but it did not agree with my dog. So perhaps you can give her a gastroprotectant she was okay with before.

I have found a previous reply from Jo to you (3/9/19) so have copied some information:

(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.
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If her red blood cells are regenerating within the bone marrow then Ezzy may be anaemic due to a gastric ulcer, or destruction of the red blood cells within the spleen etc.   With regenerative anaemia there may be an underlying cause, so this has to be investigated. Your vet will be able to tell from a blood smear if there are immature red blood cells present.

If Ezzy has a primary non-regenerative anaemia, ie., no underlying cause and the immature red cells, or precursor cells,  are being destroyed within the bone marrow, then immunosuppressant drugs such as prednisolone (and many others too) may be used.  As Ezzy has had three bouts of immune mediated disease it might be prudent for your vet to use a second drug alongside prednsiolone, such as Azathioprine, Cyclosporine etc., to give added immunosuppression and also to enable you to reduce the dose of prednisolone perhaps sooner than usual to avoid extreme side effects.

It also might be prudent, as Ezzy has relapsed, to keep her on a low maintenance dose of an immunosuppressive drug for much longer than before, to give some protection against it occurring again so soon after the last episode. Some dogs are maintained on a low dose of drug for life, and some are on a low dose for a year or so before the drug is gradually withdrawn over a period of time. 

This is a good article discussing different immunosuppressant drugs that can be used to treat AI diseases.

http://veterinarycalendar.dvm360.com/immunosuppressive-drugs-beyond-glucocorticoids-proceedings

For a dog to be in remission and then have a relapse, or develop a different AI disease, the dog has met a trigger that has caused the immune system to malfunction and target, in Ezzy's case, the red blood cells, or the immature red blood cells.  So where possible, limit 'trigger' factors such as flea treatment, vaccinations, stress etc.   If you can cast your mind back and try to remember if Ezzy has encountered a potential trigger in the last weeks, you may be able to identify the trigger and avoid it in future.

The correct treatment regimen is crucial to the outcome and this protocol by Prof Day is the best I have come across and it can be confidently used as a guide.

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.


If Ezzy is on the correct drug and protocol then if she has non-regenerative anaemia the you should see a rise in red blood cells within 5-7 days.

[tildesaz]

Thank you so much!! I couldn't find my old posts so that's really helpful!
Yep platelets are fine this time.
She's 17.5kg when they weighed her last week.
She's never been on a tummy protectant before so this is all new- she doesn't seem to have any side effects so I will bear with it.
I've got no idea what's triggered it this time- before there always has been something but not this time.
We weaned super slowly in 2020- she was on one tablet every other day for months but then developed Cushings so we had to stop.
I'm hoping it's one of the other meds that is coming tomorrow- my husband took her last week and couldn't remember the name.

Would she only need a blood transfusion if levels were at a certain point or if she was symptomatic from being so low?

Thank you again

[Catherine]

If you click on your name (tildesaz ) on the heading of your post it will bring up your summary. To the left will be your profile and you can click on "show posts". You could also use the search facility on the main page.

How is Ezzy? A PCV of 12 is very low and it may be that a blood transfusion is necessary. But if she is coping well it may not be necessary. I think I would have her PCV tested tomorrow to see how things are.

Try not to worry about the trigger at the moment, you have enough to concentrate on with starting her on the road to recovery. I know it is so stressful and demoralizing but you have done it before and Ezzy is still so young so hopefully she will bounce back again.

[tildesaz]

Ah perfect I've found them all.

She's actually fairly well. She's up and about- asking to go out. Wagging her tail and is more settled this evening with both heart rate and resp rate. I think a PCV tomorrow would be a good idea too- the vets were worried it wasn't long enough since fri to show a change but I will be happy if it's stopped falling!

Am feeling more positive this evening- this forum is so helpful xxx

[Jo CIMDA]

HI

I am so sorry that you are all going through this again, although from your description of her improvement then it could be that the preds are working and her PCV is increasing - fingers crossed.

You ask about Omeperazole?  Omeprazole should not be given within one hour of giving other meds because it could inhibit the absorption of other meds.  The rule is to give Omeprazole either two hours before other meds, or one hour after other meds.  This time lapse minimises interference between drugs.

A very good immunosuppressive drug that is being used more and more these days is Mycophenolate Mofetil (MMF).  It needs about 4 days to have full effect and it can be used as a primary immunosuppressive drug or used alongside prednsiolone.   If both drugs are used then the pred can be reduced much sooner than usual.

Try to think back to what may have triggered this relapse.  If it is non-regenerative anaemia then the trigger would possibly be about 6 weeks ago.  If it is regenerative anaemia then it may have been in the few days prior to you noticing.

I hope you get good news today.

Jo

[Catherine]

When my dog became ill with AIHA and her PCV was very low I was having her blood tested every 3 - 4 days and we would not reduce the steroid until we had seen the latest result. Certainly at a PCV of 12 I would be testing today just to make sure that it had not dropped more. If it had then, probably a transfusion would be needed. But if (and I really hope this is the case) it has started to go up again (even if only a little) then you will know things are working and have to be given time. I think it also helps the owner to feel more confident and relax....a little. Some dogs can be, in theory very ill, with a very low PCV, that may have been going down for some days, weeks. They may appear perky so this is why blood tests are a good idea. It is the same with IMTP, not all dogs show signs until their platelets are very low.

I do hope you get positive news today. It is good that she is happier, but it is best to take things gentle with her, not too much excitement, just a short walk around your garden away from other dogs and germs at the moment. You probably read about all that before but it is a lot to remember when you are so worried.

[tildesaz]

So she's down to 11. They are rechecking Friday and don't want to transfuse at the mo.
We have a prescription for the meds Jo recommended. They had ordered some in but the capsules are 250mg and too strong for her so now trying to source some syrup!
No one has anything in Cornwall

[Catherine]

When did Ezzy start the Preds? Had you been giving the Omeprazole apart from medication like Jo said? I did not realize about that.

Are you talking about the MMF? Have you considered Azathioprine? It will take time to work but I used that for my dog with AIHA with no problems.

Hopefully Jo will be able to advise soon.

[Jo CIMDA]

Hi

At 11%, your vet should be seriously considering a blood transfusion now to buy time. 

If it is non-regenerative anaemia then it will take at least 5 days to see any improvement, and that is if the pred dose if significant enough and if her bone marrow is able to produce .  It can take up to one month for the bone marrow to kick in.

I do hope your vet will take advice from somewhere like the Royal Vet College or Langford, Bristol.  They are always happy to advise.

All the best

Jo

[tildesaz]

She's started the MMF today.
Her gums are showing colour today so I'm hoping that's a good sign. She's back on Friday for another review.
Yep have now been giving the pred at a separate time- I'm cross at the vets as I had asked that and she said it didn't matter. Hopefully we are on the right track now.
Keeping everything crossed xx

[tildesaz]

I've just found a growth on her leg- wondering if this is the trigger!

[Catherine]

I am glad Ezzy seems better, hopefully you will get promising results tomorrow.

I would not panic about the lump it probably is not anything bad. I have not heard that can be a trigger. Triggers can be: vaccines, worming, flea treatment, noise (fireworks etc.) hormones - seasons, whelping, and chemicals. Two that I think people can forget and may be triggers are stress - separation anxiety, humans arguing and .....medication! Yes, a lot of dogs are prescribed unnecessary medication and it could be a trigger including some antibiotics, potentiated sulphonamides etc.

[Jo CIMDA]

Hi

If Ezzy's red blood count is less than 12% tomorrow then I would seriously ask for a transfusion.  Non-regenerative anaemia can lose approximately 4% of cells every day, so when the count is very low, testing should be done very frequently.

Fingers crossed

Jo

[tildesaz]

Sorry this didn