Bluebell

[Bbell]

Hi Everyone,

My girl Bluebell was diagnosed late 2015 \ 2016 with IMHA, after a battle we got that under control. Approximately a year later we had weaned off all meds, but this only lasted 1 week. Early 2017 she relapsed / developed IMT. This is where we have been since. Yoyo-ing numbers and no successful weaning protocol. Last wobble was at Xmas, a change in cocktail of drugs (swapped out Atopica for Leflunomide) saw a huge rise in platelet numbers but since then a constant gradual decrease. We are currently at 80.

She isn't crashing (partly because the vet and I are catching any anomalies in behaviour / readings early) but isnt getting better either. They seem reluctant to take her spleen out but I wonder if this might have to be our next step?

She is definately not adhering to normal protocol and so 2 years on we're still on Prednisone, with all its horrid side effects.

Any advice or thoughts greatfully recieved xx

[Jo CIMDA]

Hi and welcome

I am sorry Bluebell is having this problem.  Is it only the platelets that are low or does she have IHMA as well? 

I don't know what dose of prednisolone she is on or how much she weigh etc.,  and the drug regimen she has been on so it is difficult to comment.  If the leflunomide isn't working then the vet could introduce azathioprine or mycophenolate to give more immunosuppression.

If her platelets get very low again they may consider using a drug called Vincristine to boost platelet production or a transfusion of human IVIG. 

http://www.cliniciansbrief.com/sites/default/files/attachments/CoC_Canine%20Primary%20%28Idiopathic%29%20Immune-Mediate%20Thrombocytopenia.pdf

The bottom line is they have to find out the cause of the IMTP.  It is primary or secondary to other disease.

http://veterinarymedicine.dvm360.com/overcoming-diagnostic-and-therapeutic-challenges-canine-immune-mediated-thrombocytopenia

Perhaps you can cast your mind back to the circumstances that caused a huge rise in platelets (changing drug) and why they then started to fall.

Jo

[Bbell]

Hi Jo,

thank you for your reply. Its such a long story I didn't know where to start!

She was diagnosed with IMHA in 2016, and that was a battle in itself but after a year or so her red cells were behaving, then a relapse in 2017 but this time it was IMT and has been since. It is currently only the platelets that are an issue.

She is a 6yr old Lurcher, currently 22 / 23kg and our latest protocol (since December) from the RVC in Hatfield was 40mg Pred, 40mg Leflunomide and 1 tablet of Denamarin. and after bloods to check every 2 weeks, we have been reducing , we got down to 20mg per day, bloods were checked, then the next part of the protocol was and currently is 30mg every other day. So it was an increase but not every day as before. I was uneasy from all the information I have read but we have previously tried weanings and failed so I thought maybe this would work, and i wasn't making it up, it was the RVC's protocol.

Can you put them on 3 immunosupressives? and does that mean you can lower the dose of each to balance it?

She has had Vincristine before, I believe you cant have it more than once? she also had the IVIG once or twice before. (that may be the other way round! it will be correct in my notes)

They did initially look into a cause but came back idiopathc.

---I apologise if I'm rambling with no order ---

She had been on Cyclosporin since the beginning of even the IMHA, but the new vet we saw at the RVC at Xmas swapped this out for the leflunomide. This is where her platelets went from 21 to 354 !! I thought that was amazing / hard to actually believe, but since then its gone down ... 139, 112, and last friday 80.

One of my local vet seems to always choose the 'increase pred and wait two weeks' option but that doesnt solve anything - I am due to see my vet again this morning as she has been vomitting since the change in protocol, I am preparing to be quite brutal in terms of her long term prognosis because this is no fun for her.

I dont believe we can carry on yoyo-ing, increasing the pred as soon as we dont like the numbers. she is clearly a refractory case and Spleenectomy has been mentioned but not seriously concidered by the vet or specialist so far.

I have noticed that it has been every february that she has a downturn - hardly a medical conclusion though! 

I really appreciate your taking the time to reply x

[Jo CIMDA]

Hi

It seems as though so many things have been tried, but like you say they haven't considered a splenectomy.  I wonder why?  How did you get on at the vet's yesterday?   Have you discussed a splenectomy with them?  I have known some dogs to have a yoyo effect of low platelets and also red blood cells and if it remains refractory then a splenectomy often does the trick. 

Yes three immunosuppressive drugs can be used at the same time and this is usually done to enable the preds to be lowered because long term, high doses of  preds cause the most serious side effects. The immunosuppressive effect of several drugs is accumulative, but of course it has to work.

I presume the RVC raised the preds to 30mg but gave it every other day in order to limit the side effects of the preds, but anecdotal evidence suggests that relatively high doses of preds given EOD rarely achieves the aim.

The RVC is an excellent referral centre and I feel if anyone can get Bluebell over this they can.   I think you should ask about the possibility of removing her spleen. Also they might consider changing from leflunomide, because it isn't agreeing with her, to mycophenolate and perhaps adding melatonin.

I hope you have a better result from the last blood test.

Jo

 

[Bbell]

Hi jo. The vet trip was awful in terms of results. Pancreatitis and further bloods reveal platelets have dropped to 27 I'm gutted and don't know which bit isn't working. We have gone back to 20mg a day rather than 30 EOD (which was as you observe, to limit effects and get her body to start working again). And added some famotidine, mecrobactin and cerenia (spellings?!)
I'm at loggerheads with the vet at rvc, she was totally blinkered and when I suggested mycophenolate she said no, leflunomide, !and when I suggested melatonin, she sad it's not proven, she said that about any of my suggestions, all of which I have got through groups such as this. But who am I to argue with leading vets at the rvc ?! I'm a no one to them and all they see is a list of suggestions I have with no clinical evidence it's so unbelievably frustrating.

Can I swap leflunomide for mycophenolate without quibble, just swap or needs to be tapered somehow?

Can you help me understand why melatonin will help? I guess its helps with stress levels? I have seen the suggestion a few times before but never really understood how it will help. (This is why I couldn't argue my point with rvc when she poo pooed it)

I guess they wouldn't consider surgery (splenectomy) if her platelets are so low?

Thank you jo for your help x

Further information: I have just spoken to my vet, who has spoken to rvc. It has been suggested I go back up there to re evaluate whats going on. I will be asking to see a different clinician.

[Jo CIMDA]

Hi

Is Bluebell showing signs of bleeding and bruising because she should be if her platelets are only 27?  If she is not then I would question the sample taken and ask if there was clumping.  If clumping is evident then the platelet count is much higher. Also the automated count should be confirmed by a human count taken from the slide. Clumping doesn't mean that she does not have thrombocytopenia but it may not be quite as bad as you fear and I have also known a dog who periodically showed very low platelet counts without clinical signs and this corrected itself time and time again.  Why this is I don't know but have a read of this paper, it is very comprehensive:

http://www.eclinpath.com/hemostasis/disorders/platelet-numbers/

Another thing to consider is sight-hounds can naturally have a lower platelet count than most other breeds.

I have always considered the RVC to be one of the best referral centres,  BUT so much is down to the individual vet's experience and just because they are 'specialists' doesn't mean they know everything and  they don't always know what is best practice in an individual case. Also, the person you are seeing may not be a qualified' specialist' and may only be doing their training in their particular specialised field. 

I lost my Bonnie to a 'specialist' vet who overdosed her with prednisolone.  I argued with this vet that the dose was too high and she told me if I lowered the dose of preds "I would kill her".  Well, against my better judgement,  I listened to this specialist and my Bonnie died as a result of the preds being too high.  The specialist told me after Bonnie had died that she had since been in consultation with someone at Cambridge Vet School and as a result of Bonnie's death they decided that larger dogs don't cope well with high doses of steroids and from that time this fact is well documented.  So although I hold the RVC in high regard I can say with my experience, and the experience of so many other pet owners, that  just because their title is one of a 'specialist' that doesn't mean that they know how to treat the animal in their care.

Where in the country do you live?  I may be able to recommend a better referral specialist or practice.

What is not clear is why, as Bluebell's IMTP is refractory, they are not trying everything - why not try Melatonin?  Why not change to another immunosuppressive drug?  What have you to lose?  Clearly, if Bluebell's platelet count is accurate then she cannot have surgery at this time.  This vet at the RVC has to have a superior, a vet above her that is more qualified and with more experience, so I would ask to see her superior.   Prof. Brian Catchpole is the Head of Companion Animal Immunology at the RVC and I have always found him to be really lovely.

https://www.rvc.ac.uk/about/our-people/brian-catchpole

It might be worth asking to see him or at least have him look over Bluebell's case.  You are paying for Bluebell's treatment then you are surely entitled to see the best.  Prof Catchpole may not see individual patients but that wouldn't stop me from asking him to review Bluebell's case. Alternatively, Prof. Michael J Day is based at Bristol Vet School, Langford, and he is the one-to-go-to for anything to do with immune mediated disease.  The specialist at the RVC could contact him by email or telephone.

They can swap mycophenolate for leflunomide .  This is a very good source of information about immunosuppressive drugs.

http://veterinarymedicine.dvm360.com/immunosuppressive-drugs-beyond-glucocorticoids?id=&sk=&date=&pageID=5

The best immunosuppressive drug is prednisolone but the side effects after prolonged periods of use may prohibit them being used as a first line immunosuppressive drug in refractory cases.  If Leflunomide is making Bluebell sick then it is wise to change to another drug.  It clearly doesn't agree with her.

You do have the option of finding another specialist to look at Bluebell's case.  You don't have to stick with the vet at the RVC.  Always remember you are paying for their services and if it is not good enough then you have the freedom to find someone else who is better.

I am in total sympathy with you and I hope you can get this resolved for Bluebell. 

Jo

[Jo CIMDA]

P.S.  A little more for you to digest.

Don't accept the excuse that nothing has been proven about Melatonin. 

Vets use off label (human) drugs all the time when treating of animals.

  So many of the immunosuppressive drugs are not licenced for animal use but thankfully they are used because they have proven to be useful in human medicine.

Sometimes, unbeknown to the owner of the animal,  a drug is used as a clinical trial .  If my dog is being treated for a condition I don't want them on a clinical trial I would want them to be treated on an individual case basis and given the appropriate drugs for that condition and if one drug or a combination of drugs don't work then I would want the drug regimen to be changed.   

How about this.  I have not heard of Romiplostim  but it is worth consideration.


https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-016-0718-4

Melatonin is not used as a sole medication but it has been proven to assist with immunosuppression.

A bit about Melatonin:

https://www.dovelewis.org/pdf/events/Immune_Mediated_Thrombocytopenia.pdf

Melatonin (pineal gland hormone) has been shown to stimulate platelet generation, probably by promoting megakaryocyte fragmentation as well as by altering the cytokine network involved in platelet production. A human study has shown that melatonin (20mg/day) rapidly and significantly increased the mean platelet count in 72% of patients with ITP. No veterinary studies have been performed, but a suggested dose of 3-6mg PO q12-24 hours has been recommended by some clinicians, and melatonin seems like a low-risk and potentially helpful adjunctive therapy for ITP. The main side effect is drowsiness.

In human patients, additional therapies are currently under investigation. These include rituximab (a monoclonal antibody directed against a specific B cell antigen) as well as romiplostin and eltrombopaq (thrombopoietin receptor agonists). However, there is currently little experience with these medications in veterinary patients.

http://veterinarymedicine.dvm360.com/just-ask-expert-there-role-melatonin-dogs-and-cats-with-imha

Jo

[Bbell]

Jo, I cant thank you enough for your wealth of information. I will look at all the links after tyoing this.

no signs of bleeding, no petechia, she never has bled from any orifice when her platelets are low. Her very first symptom, ever, was significant petechia on the insides of her back legs but that was IMHA, since then only minor 'blobs'. Reading back through her notes, on very first admission they seemed confused as 'immune problems don't present with other symptoms'.

Usually they say there was clumping, but this time, clear mention that they could not see any.

I am in Berkshire, Maidenhead.

I must admit I feel (from the conversation with my vet this morning) that the chat she had with the RVC, and a different clinician to the one I saw in Decen=mber, that they are keen to try a few other things right now. just a feeling I didnt get from the last woman!

Off to read up on the links ... and get a load of questions for the rvc. I had a wobble about changing them at Xmas but thought, better the devil you know, they knew BB's history and I know they have a great reputation, I didnt want to risk getting more involvment from other practices and further ideas / protocols. I just felt / feel like my knickers are in a right twist. That said I have not ruled the option out.

I am so very sorry you lost your sweet Bonnie because of bad information, its such a difficult journey to manage when you have no idea whats going on, you can only do what you think is right at the time  x

[Jo CIMDA]

Hi
Spontaneous bleeding can and is very likely to occur when the platelets are below 40. 

I am so pleased you are getting a better response from the RVC.  I wished I had exerted my rights to be listened to.  Don't forget you are paying the bill.  Also, if you think that they want to do unnecessary testing, procedures etc., don't be afraid to say you can't afford it!  You will be amazed the different response you get if the procedure or testing is not necessary. 

FYI

There is an amazing  specialist vet called Kit Sturgess. He seems to have a link with, The Vet in Morden Surrey, which is 43 miles away from Maidenhead.

https://www.thevet.co.uk/quality-veterinary-care-kit/     

I believe he also does a few days at Optivet in Havant, Hants. This is further about 75 miles away from Maidendhead.

http://www.optivet.com/


There is an excellent referral centre called Anderson Moores in Winchester.  It is a bit further then the RVC but not much.  It's just under 50 miles from Maidenhead

Wey referrals is about 27 miles away in Woking, Surrey.

http://www.any-uk-vet.co.uk/wey-referrals/index.htm

I hope you don't feel it is necessary to move from the RVC but don't hesitate if you feel you have to .  There are several options for you to choose from.

Good luck

Jo 

[Bbell]

Thank you, I have been recommended Anderson Moores before, but then Bluebell took a turn for the better so didn't feel the need to change at the time, its great there is another thumbs up for them.

We are booked in for next Thursday. Will update then

[Jo CIMDA]

Hi

Anderson Moores used to be Anderson Sturgess. Kit Sturgess started it.

I am concerned that she has a very low platelet count and your appointment isn't until next Thursday.  Are you going back to your own vet before then to see if the platelets reduce even further - or even increase? 

I know you are used to this with Bluebell but, from where I am, platelets can drop dramatically fast at times.  Keep and eye on her levels.

Jo

[Bbell]

Hi jo,

I managed to move it to Wednesday but that's the earliest they can do. I too am cautios knowing her levels are so low. I am not due back to my own vet, no. I am keeping an eye on her ,  but I realise things can happen hidden, internally too.

will call my vet now
x

[Bbell]

Hi Jo, I got a referral to Anderson Moores this afternoon, she is staying in over night. They were singing RVC's praises, and didn't seem , if I'm honest, that they would be able to do much more.

However, as you say, at least she will be there should anything happen. I will still go to the rvc and try to remain primarily with them as the specialist, at least now I will have had a fresh pair of eyes on it.

thank you for your continued support and concern x

[Jo CIMDA]

Hi

I think this is a very wise move.    They will not say anything against the vet at the RVC even if they thought it, but it is always worth getting a second opinion.  Sometimes getting another vet to look at a case is the the best thing that can happen.  Given Bluebell's low platelet count it is prudent not to leave it a week.

Fingers crossed.

Jo

[DW]

Hi
It has been a long time since I have commented on this Group but I have constantly maintained an interest in the messages.
Jo will know why this one interests me particularly and I would like to add a little from my own experience with Harley, who, sadly passed about 12 months ago, after a 6 year struggle with IMT, due to a malignancy on his liver.

Melatonin has been mentioned and whilst I appreciate that the RVC state nothing has been proven (and in a way they are right) I suppose you have to say that many of these drugs may work for one and not another......I have known steroids not to work as well for some !!!
In our case, we had tried steroids with Azathioprine, we tried Cyclosporin (after considerable resistance) but nothing seemed to work.
Whilst he was steroid-responsive and we would frequently stabilise his platelets - remissions were short-lived and we went through
several relapses.
Melatonin was suggested as, I suppose, a last-ditch attempt to regulate.  I'm afraid I was at the stage at the time, that I would try anything at all.   I learned that in the US Melatonin was often used at the start of IMT being diagnosed (with or without steroids) and the responses seemed positive.....so we tried.      We used 6mg dose and chose to buy Circadin, which was a more expensive way of buying them and I had to have a prescription for them.     The evidence has been anecdotal mostly and could well have been successful in part to additional and lengthened term on immuno-supp. drugs but in our case, we started on this dose of 6mg and it took a couple of weeks or so before we started to notice 'slight' increases in his platelets.    We were on, at the time, 30mg prednisolone and we continued to use the Preds, reducing them strictly in accordance with Prof. Day's protocol but we kept to the same dose of Melatonin throughout.   The platelets reached a really good level and maintained this count and we were able to eventually get the preds down to 5mg daily and then, taking things even more slowly, down to 1mg - eventually taking him off the preds completely and just using the Melatonin.   The platelets maintained at around 300 and did so for a few months but sadly, he relapsed - platelets went down to 20 and it was then we discovered the problem with his liver.
I don't know if the Liver problem was always there  or if, the years of being on steroids took their toll or that the Melatonin actually weren't able to work on their own but I am sure that the Melatonin did have a positive effect and had it not been for his Liver issue, I 'feel' that in Harley's case, the Melatonin may have been able to control his IMT.....we will never know.
I suppose what I am saying is.....read up about Melatonin.  It is a drug that has a hormonal effect and whilst normally used to aid sleep, has been found to increase platelet levels and there are plenty of articles written if you look, that confirm it's usage for IMT - though there are no guarantees...but isn't that the same with any drug?
Our recommendation came from a Vet at a referral centre and someone I had an awful lot of faith and confidence in.  We spoke about 'anecdotal evidence' but both still though it was worth trying.
Hope this helps a little in some way.
Gwyneth