Page 53 – Second Chance AIHA Dogs

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Keymaster

Hi Hope,
I use the CAPC Parasite Prevalence Maps to determine in general what tick diseases are active in locations. I get that information mailed to me each month about my state, my county and my surrounding counties. This information is collected through REPORTED cases from vet clinics and doesn’t reflect cases that have not been reported. They advise “The data in this update and in our maps was provided by IDEXX Laboratories, and ANTECH Diagnostics. It is statistically significant and it serves as a strong representation of the parasite activity for each area. However, it does not represent the total number of positive tests. Instead, we estimate it represents less than 30% of the activity in the geographic regions. Stay tuned as we send you updates for your area! ”

I think I can assume you are located in Louisiana near the coast? Checking that map for you indicates a very high rate of reported cases of heartworm disease in the state. While some counties may appear to have less reports, this usually occurs because vets in those counties may not test at all or use a different lab to test with. I don’t think mosquitoes or ticks honor county lines ;-}

There are some hotspots of roundworm and hookworm along the southern coastline.

Lyme disease is apparently less reported in the state, with a few counties showing a high rate of reports.

Ehrliciosis seems to be more prevalent in the northern area of the state, but there are enough reports of positives near the coastline to be concerned. This particular tick disease is very dangerous and can literally cause AIHA.

Anaplasmosis seems to follow the same trend of Ehrliciosis, it appears spotty but has some higher incidents in a few counties. This is another disease that can impact the circulatory system.

So for each report it indicates that there are major tick diseases, parasites and Lyme disease in Louisiana. So exposure is possible.

Prevention is the best way to protect against tick diseases and mosquito disease such as Lyme. Counting on being observant and finding them is nearly impossible. Some ticks can be very tiny and be missed easily and mosquitoes are SBD. I know this because I missed a tick on Willie earlier this year before the weather had warmed over 50 degrees here in upstate NY! We had to treat, assuming that he had been exposed. It was a lengthy treatment and very expensive.

I would suggest, after you have made preparations to prevent exposure, is to take him to the vets approx. 6 weeks after the trip and have the vet do a SNAP 4DX test which will test for everything I mentioned (except the worms). This will cost no more than $45 and will take a tiny blood draw and the yes/no results will be ready in 8 min.

Have a wonderful visit with your family!
my best
patrice

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Patrice

Keymaster

Tamara,
To respond to you I need to draw some important differences in how Dr. Dodds approaches (and approached with Chance) bone marrow failure in a dog. It is significant to note that she has been recognizing and treating this condition for a very long time. In 2007 even my renowned Diplomate Vet specialist was confused by Chance’s bone marrow failure and could only offer a guess that it might be autoimmune related. But as far as treatment, he offered little help or hope and prescribed only prednisone. Chance was not responding to this treatment.

I have helped many owners since then whose dogs had severe bone marrow failure. Many of the vets they were working with appeared to not be cognizant of how and why this condition appears in dogs. Nor in some cases did they understand how to properly treat this. Thus it also appears that they could not fully understand canine physiological response to treatment.

In intractable cases of bone marrow failure in dogs, Dr. Dodds knows from experience that many dogs have an autoimmune component and often autoimmune hypothyroidism. Many vets first seem to jump to the conclusion that this is a form of cancer. That essentially bypasses a series of diagnostics that Dr. Dodds normally recommends first before immediately doing a bone marrow biopsy. She points to investigating autoimmune hypothyroidism, a drug the dog was recently exposed to, a recent vaccination, toxic exposure, recent surgery, hormonal influence, infection or injury. You and I have talked about how I felt, from reviewing his blood work, that he was undergoing a inflammatory response to something and I thought that his digestive problems were related. A benign tumor probably wouldn’t be directly related, but if a spider, bee or snake bite occurred in this location and became infected it is possible that one of these insults could enhance an autoimmune reaction.

Years ago, Dr. Dodds recognized that bone marrow failure in dogs could be caused by an autoimmune attack on the precursor cells (stem cells) of the bone marrow by the T-cell lymphocytes. In her early career she had been involved not only in veterinary science but also has an extensive resume working in human hematology and immunology. Her experiences may have exposed her to the use of cyclosporine to treat humans with organ transplants. Clearly her understanding of how this worked in humans prompted her to explore using it in dogs with bone marrow failure and AIHA.

So this brings me around to how Chance was dosed with cyclosporine by Dr. Dodds for his severe non-regenerative anemia and neutropenia. She used “pulse dosing” with him, something she often recommends for dogs with intractable bone marrow failure. This concept is sometimes used in dosing with herbs. The idea being that constant exposure to an herb or drug on a daily basis begins to blunt the response by the body. Giving a few days off between dosing seems to resharpen the bodies response to the drug.

So she first started dosing Chance at a “Loading Dose.” (10mg/kg) The recommended higher dose for Atopica quickly brings the blood level up to a therapeutic dose, “jump starting” the treatment by saturating tissues. But to this dosing she also added the pulse dosing, so he received his Atopica Monday through Friday and had a drug holiday Saturday and Sunday. After 3-4 weeks of this dosing schedule she had me reduce the Atopica to the normal dosing. She continued him on the M-F, SS off, dosing schedule. Within the first 3-4 weeks he became regenerative.

I often read that vets want to test the blood level of cyclosporine to ensure that it is in the correct levels. I have explained the history of this with human organ transplant to you already. There were two formulations of drugs and they were being used interchangeably. It was not apparent until after some time that one formulation had a much more variable absorption in the body and patients were sometimes not getting enough of the drug, thus the eventual required testing of blood levels. When they discovered this it was recommended that they use the formulation that was more stable and absorbed at a constant rate. This is the formulation they use in Atopica and generics of this drug now for dogs.

So it isn’t usually necessary to test the blood levels of this drug in a dog because they are receiving the correct formulation that ensures proper absorption as long as it is dosed according to the recommendations and is being properly given without food. I asked Dr. Dodds about this early on and she told me not to waste the money testing. We would know soon enough if this was going to work and in fact she was quite correct.

But secondly, think about how Dr. Dodds doses these dogs with bone marrow failure, she uses pulse dosing. Taking the drug away for two days in a row should negatively affect the therapeutic value of it, right? But it doesn’t and Chance is a perfect example of that. The drug was MORE effective being given only 5 days a week with two days off. This blows the whole concept out of the water that this drug is only effective at a certain daily dose (to maintain blood levels) and any dose below that it is not effective. Your vet is telling you that the drug is either on or off, that there is no level of efficacy at a lower dose. From my experience it maintains a proper blood level even with pulse dosing!

So yes, I did targeted decreases. I used a 33% reduction rate, approved by Dr. Dodds. I had to fiddle with this a bit because Atopica only comes in certain capsule sizes. I extended this decrease period out a little longer because Chance had allergies and I wanted to keep him on it into the worst allergy season in the following year. This drug is intended to be given to dogs for a long periods of time for allergies and has been tested to show that it is safe and effective dosing this way. So if this were my decision I would continue it and begin the decreases as I have described, 33% at a time.

If there is a relapse it will be less complex to just increase the dose some rather than go through a loading dose to get his blood saturated again.

I would recommend you reconnect with Dr. Dodds about the reduction. I would trust what she tells you.
my best
patrice

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Patrice

Keymaster

Hi Tamara,
Excellent questions!
1. Weaning of prednisone is generally based on three criteria. The first is to determine if the dose is leading to severe side effects that are actually worsening the condition of the patient. The second is if the vet has been able to successfully transition the immunosuppression to another drug. So in your case, transitioning to cyclosporine is in place. The third is how successful have you been at halting the hemolytic destruction and is there either a rise in hematocrit (PCV) or have you been able to stabilize at a level that is supportive enough. Since Ashki may not have been destroying red blood cells in circulation, this isn’t a consideration.

2. Our combined experience, as moderators, and combined with the recommendations by Dr. Dodds and other resources such as attending vets has led us to recommend to start the reduction of prednisone as soon as is practicable. The general percent is approximately 25-33% of the current dose (I like to figure this out as a weekly dose and work from there.)

3. The decreases for prednisone should not happen sooner than approx. every 2-3 weeks. Each decrease should be preceded by a complete CBC. If you are feeling unsure about this then you can request a weekly PCV to be spun to ensure you know that Ashki is stable. The next decrease can occur in about 2-3 weeks provided that there has been no negative change. Ideally, the goal is to reduce this values down below what would be considered immunosuppressive. This is obviously different from dog to dog due to considerations such as size! But in general when you start getting down around 5mg a day (unless it is a tiny dog) you are not in the immunosuppressive range. Some dogs may never be able to completely eliminate prednisone in their lifetime, but for others is isn’t necessary.

Decreasing atopica (cyclosporine) should not occur until there is a completely stable HCT (PCV) at least nPCar the lowest normal range of about 37-39%. (And this can occur alternatively with decreases in prednisone.) However, that said, the dosage for this drug should be approximately the same as the normal dosing for a dog with allergies (which is what Atopica is actually prescribed for.) This drug acts differently than prednisone and controls the population of T-cell lymphocytes. At that maintenance dose suppression should be happening properly. Cyclosporine does not need a complex decrease schedule for safety as prednisone does. It needs to be decreased purely by the results you are seeing with the HCT and the reduced numbers of T-cell lymphocytes.

As Chance had bone marrow failure I focused on getting the prednisone dose reduced as much as I could as it was making him ill. Once that dose was lowered significantly, and he had reached a HCT of about 36-37, I began alternating the reduction between atopica and prednisone. I conferred with Dr. Dodds at each step to see if she recommended what I had determined to be the next reduction.

4. A relapse in a dog that has had bone marrow failure is a bit more complicated to examine. The HCT is not the sole value to be looking at. Evaluating at each step in the reduction should also be accompanied by examining the reticulocyte value. A dog or human with a normal HCT (37-45 for normal dogs) should maintain AT LEAST an absolute value of 60,000 circulating reticulocytes (approx. 1 to 1.5%). If a dog’s HCT has declined slightly during recovery to, say, 33% there should be an accompanying increase in the reticulocyte value. It may be small, but it MUST be more than 60,000 absolute and 1-1.5%. There is no wiggle room on this. If you see a decrease in HCT with no accompanying increase in reticulocytes you must consider that the bone marrow has become non-regenerative again. In that case, if it is slight and Dr. Dodds agrees it is slight, you may want to only increase the dosage of the cyclsporine back to the original dosage. Monitoring the value of lymphocytes helps you evaluate how successfully this worked.

If, however, there is a gradual and definitive decline in HCT over say, a period of a month, you may need to once again add back in prednisone. At this point I would have not made any decisions on my own but would have gone back to Dr. Dodds for help. Any choice to begin increasing prednisone introduces the side effects that make a dog’s health suffer.

As always, in dog with significant bone marrow failure, other factors need to be evaluated such as gastrointestinal health, proper nutrition, other conditions that may be impacting such as liver, kidney, thyroid, heart health. A continuous mild anemia can be related to anemia of chronic disease. That would need to be treated and no manner of immunosuppression would alter that.

There are no hard and fast rules, every case is different. The best thing you can do is continue to remain a frequent visitor to the vet’s office, stay in contact with Dr. Dodds and keep scrupulous CBC records. If at any time anyone needs help evaluating the CBC, I can and will do that for you if you need help. I know how to work the math carefully because I did this for Chance for over 6 months.

Do dogs that have had bone marrow failure return to normal? Yes and no. My vet did a study of all the dogs in her treatment memory that had a spleen removed and/or had bone marrow failure. As I had expected most of these dogs never return to a HCT much higher than 36-42. She could not explain that, but indicated that was Chance’s new normal. How did we determine it was his new normal? Simple. His reticulocyte value always remained at 60,000 (1%) which indicated his BODY WAS HAPPY AT THAT HCT. So in the future you will want to use the recticulocyte value as Ashki’s guideline for good health.

Have I answered your questions well enough?
my best, patrice

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