Pickles with NR-IMHA

Allison H

Guest

On 11/7/19 during a routine exam, our vet noticed our 8 year old corgi Pickles had pale gums. Otherwise he was still quite active (but slowing down, we thought due to his age), eating, drinking and barking like normal. She ran a quick PCV and was shocked to find it at 12%. We were sent to the emergency right away for a blood transfusion. At the emergency hospital, they ran a full spectrum of labs and tests: CBC, chem panel, urine, parasite check, xrays, and abd ultrasound. After a thorough exam and all tests being normal (other than his low rbc) the doctor suspected IMHA. She also noticed his retic count was low, so we did a bone marrow biopsy. It was then he was diagnosed with non-regenerative IMHA. His immune system was destroying his baby RBCs (reticulocytes) before they could become mature.

After hours of exhausting research, I don’t understand how IMHA could have such a sudden onset with no apparent cause. But I did look back at our timeline in the last few months. Pickles had done full blood work back in July 2019 prior to dental cleaning, which was required since he would be under anesthesia. His hematocrit was 52% back then. He then received the canine influenza vaccine in August and the 2nd booster in September. Then in November, his PCV dropped to 12%. I’m not sure if any of this had triggered his immune system to go haywire. Our vet suspects that his count was dropping slowly over the last few months and that his body has compensated which explains why he showed little symptoms of the disease.

It’s now exactly 3 weeks since his diagnosis and he has been started on prednisone 15mg BID, mycophenolate 125mg BID, Clopidogrel 18.75mg QD, and famotidine 10mg QD. We also started him on supplements: hepato support BID, blood and energy support BID, omega 3-6-9 QD, glucosamine QD, and chloroxygen drops to his water. He’s had several transfusions too. The first transfusion lasted about a week until he needed another one. Then the 2nd transfusion lasted 2 weeks and we just did the 3rd one today. But today they gave him 2 units of pRBCs instead of 1 unit because his PCV dropped to 12% again. After the 2 units, his post PCV is 32%. I hope this big jump isn’t too much too quickly….since his body had been so used to being in the 20s. The doctor also decided to add cyclosporine 100mg QD. After reading the forum here, I plan to give it to him separately from the other meds or food.

I am hoping that the meds will start working soon. Our internist vet told us that since he has IMHA at the level of the bone marrow, the meds will take time (1-3 months) to really start working. And in the meantime he will need transfusions. Is anyone here familiar with this type of IMHA? There seems to be so many different variations and very specific treatment regimens for every case. Pickles still has a great appetite and seems very happy around us. I’m glad he is tolerating all the meds so far, and has not vomited or had diarrhea. The only one is the prednisone has caused significant muscle atrophy in his face, back and legs so he cannot jump onto the couch or bed anymore without our help. The excessive thirst and increased urination is something we can live with since one of us is always home (My husband and I work opposite schedules).

This has been such an emotional roller coaster for my husband and I. Pickles has been our baby since we first started dating. We have had many ups and downs the last 3 weeks with this disease…. I am hoping we are doing everything we can but would like to know if there are any other suggestions for us to help fight this for Pickles.

Thank you.

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Patrice

Keymaster

Allison,
I am so sorry to read this. You must be very worried. We are here to help you and answer all your questions. There is a lot to cover but I will cover a few of the more important things.

This is not really IMHA, this is actually considered a type of bone marrow failure: non-regenerative anemia.

This site is dedicated to Chance my Giant Schnauzer who was diagnosed with this condition in 2007. At that time there was little information available about this condition in dogs and the specialist I saw was baffled about how to treat it. He said that Chance was a beautiful dog and I knew he was really saying there is nothing I can do.

There is a huge learning curve to understanding this condition. You have picked up on a lot of regular veterinary clinic terminology which makes it a bit easier.

So you have an understanding that the damage is occurring in the bone marrow and your vet has explained that it was probably happening over a long period of time.

So let’s look at basic hematology. Red blood cells are made in the bone marrow. I’ve read quite a bit about this and it is quite a complex process which includes “nurseries” that are extremely isolated in the marrow. There are many many steps or stages that occur. Look at this diagram:
https://www.secondchanceaihadogs.com/AIHA_Terms/hsc-hematopoietic-stem-cells
This is a simplified chart, there are actually more steps in each cell line than this. Study it carefully. In the middle you see a single cell “stem cell.” This is what we call a precursor cell. From this, all the cellular elements in the blood are made. You see there is a direct line from the original percursor to RBC. Across the lower left you see a number of white blood cells types that are related by having another stage of cellular development. At the top you see that platelets also have their own pathway. Finally in the upper right you see a second set of white blood cells, called T-cells. So you can understand how each line can have success or failure due their different stages of development that are independent of the other cells types.

So the bone marrow biopsy measured or looked for some of these cell types to figure out where the loss is occurring. But it’s really very well documented that when there is non-regenerative anemia of an autoimmune behavior, it is the precursor line of the RBC. Now Chance also had neutropenia, or he was not making white blood cells as well. So you can see how these two lines could be impacted similarly but independently of each other. His condition was even more severe because he wasn’t making white blood cells and was at great risk of infection.

Now go back and look at the diagram again. Do you see how the other white blood cells, the T-cells, are not related in lineage to any of the other cells? They are also called “Killer” T-cells. These are the elements of the immune system that are given instructions by the thymus gland to attack invaders and are quite important in protecting us. Unfortunately they are also the cells that become rogue in autoimmune conditions, ignoring their instructions and failing to recognize “self.” These are the bad actors implicated in this bone marrow failure. They are working deep in the marrow, somewhere near these special nurseries, attacking the precursor cells.

In IMHA, Immune Mediated Hemolytic Anemia, these T-cells attack red blood cells inside the blood vessels, in circulation. They destroy the RBC and all sorts of debris floats in the blood causing a great risk for inappropriate clotting, this doesn’t happen in non regenerative anemia. The damage in IMHA can be extremely rapid, within hours sometimes, and thus why this is such a crisis in emergency care. The word mediated means “caused by” and that is the goal of the vet, get the history, do the right diagnostics and then administer treatments immediately. There are usually several, if not many, triggers to the development of IMHA, a sort of tipping point occurs and then the immune system topples. Very rarely, nowadays, do vets believe this is a primary, idiopathic, condition (without a known cause.) Now they are discovering many different ways this condition is triggered. And in many cases it is based on genetic predisposition. In other words, a dog’s breed and the pedigree have a lot to do with the expression of these autoimmune cases. For instance dogs that tend to have allergies from a young age or frequent digestive disorders (sensitive stomachs) etc.

Now let’s look back at the bone marrow failure. There are very few causes for this, unlike the many for IMHA. Let me look at two of them.

We can look at nutritional causes, which can play an important role in the development of red blood cells. In order for the bone marrow to produce strong healthy reticulocytes, it needs certain critical nutrients such as iron (ferritin) and B12 (Cobalamin.) Dogs can have certain serious gastrointestinal diseases that can deplete the reserves of these nutrients. These levels can be tested, by submitting a blood sample to a lab. But a little investigative work can also lead to an answer. Any dog that has digestive problems for most of its life may be at risk for this. So one inexpensive way to diagnosis this is to try a treatment. Dogs that have or had SIBO, small intestine bacterial overgrowth, have lost the helpers that bring dietary B12 into the body. So shots of B12 may be enough to jump start the production of RBC (oral supplementation of B12 in these cases does not work due to no helpers in the cell walls of the small intestine.) It is inexpensive and easy. Iron levels are more complex but it’s important to know that dietary iron is very rarely a problem, it’s more a problem of storage in the liver. So liver integrity is important. Dietary causes of non regenerative anemia would lead to poor quality cells that would break apart in the marrow before even reaching the blood stream. This is a “maturation” defect of the cells. Physical damage to a poorly made cell.

There is another more important cause, which is actually quite common to dogs. This is what Chance and many other dogs have had. Autoimmune destruction of the bone marrow precursor cells. As I said, this happens very deep in the marrow. This is a complex condition and the understanding of this has eluded many many vets in the years we have been helping owners. The first thing they want to do is an invasive, painful and expensive bone marrow biopsy. Well, we already knew the dog was not making RBC in the marrow so this is more of a curiosity by the vet than a valuable tool to improve treatment, because they don’t understand what is causing the damage. We very rarely recommend any dog get a bone marrow biopsy in the early days of diagnosis.

So the T-cell lymphocytes attack at the deepest levels of the bone marrow. To stop this process there must be targeted and intense bursts of immunosuppressive drugs at this deep level in the bone marrow. We have seen cyclosporine be extremely effective if used at a HIGH LOADING DOSE in a pulse dosed treatment (M-F on S-S off)

When Chance was diagnosed he had been on predisone for months. His body was failing due to the high dose side effects. I began to have very little hope that we would save him. A friend told me to contact Dr. Dodds, a vet in California. I had my doubts about this, it didn’t seem right, but I was getting very anxious. I called her and she picked up breathlessly, asking me many questions. She told me this information about the bone marrow precursor cells and sent me her protocol to treat this. My vets knew of her and were delighted to take instructions to administer the treatment. We started it and within 4 weeks Chance began making RBC and WBC. The short of the story is he recovered and within the end of the year he was back to good health.

So what is happening in this disease? Let’s call it by the official title normochromic, normocytic anemia.

We make RBC every day of our lives. Our bodies destroy old worn out RBC every day also, at about 120 old. But we don’t destroy them all at once, just a small number each day so the destruction occurs spaced out over time. So this is what has been happening, the red blood cells were slowly being destroyed when their time came, as part of a normal process. The cells in the blood were all normal, thus the terms normchromic, normocytic. The cells contained the right amount of hemoglobin (the chromo part) and they were the correct size and shape (the cytic part). So all the cells in circulation are doing a normal job, but there are fewer and fewer of them. Dogs that loose their RBC population this way are not at great risk of having an emergency, they are slowly losing the RBC and their PCV HCT drops very slowly. That was what we found with Chance. He was diagnosed first at 32% and then it slowly dropped to 18%. Dogs are all different in how low they can drop without observable symptoms. His low number was 18%, but he also had terrible side effects from prednisone. On that day, he couldn’t squat to do his business and I called my vet right there on the sidewalk to ask her to do a transfusion. Some dogs can be walking around fine at 12%, others are genuinely miserable at 32%. So we call this a transfusion trigger. There is no one single HCT where we MUST transfuse, it’s a judgement by the staff that is dependent on behavior, symptoms and data. If a dog is weak and losing appetite etc then a transfusion is probably needed. The down side in non regenerative anemias is that transfusions can lead the body to not really try hard enough to begin regenerating, so we don’t always urge owners give a transfusion unless the dog is really having problems like difficulty breathing, heart murmur etc.

So here is the link you are going to look at first. This is where you will contact Dr. Dodds for a second opinion.
https://labordatenbank.com/cake/hemopet/onlineorders/hemopet_add

This is Dr. Dodds consultation test form, She will want to see the most recent CBC and chem screen. Vally’s suggestion is to scan all these items together in one file and send just the one, not multiple forms, which will not send properly. With this consultation she will evaluate your tests and recommend any alteration in the treatment. She will be available to you at future dates for more questions. I can tell you that the treatment on this protocol is what saved Chance. She recommended cyclosporine (Atopica) at a high loading dose, pulse dosed (M-F on, S-S off) and cycled like this up to 4 weeks. He was responding by the fourth week.

She’s been treating this condition in dogs this way well before she helped me save Chance’s life. Her complete protocol to treat this conditions is exactly what I used to save Chance. We have recommended consultations with Dr. Dodds many times. Just a few days ago Coco’s owner posted her success story with Dr. Dodds consultation, see her topic Coco Is Improving, just below yours. This is a typical multi approach to treatment.

She will look over the treatment protocol you are on and make some recommendations.

One of the drugs you are using is Mycophenolate. This is a human drug used to prevent organ transplantation rejections. Some of the dogs we have seen put on this developed digestive problems, including bloody colitis. I am not a fan of its use, it hasn’t been fully tested for veterinary use. Let’s see what Dr. Dodds thinks.

Another drug that is usually very important in treatment is the addition of thyroid supplementation. “Endocrine disorders, such as hypothyroidism and hypoadrenocorticism, can produce a mild to moderate normocytic normochromic anemia. ”

Do you have more questions for me?
My best Patrice

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Allison H

Guest

Thanks for all the info Patrice!

I am in the LA area so my vets are very familiar with Dr. Dodds. Her Hemopet clinic is nearby in Irvine. I have not consulted with her yet. I am also a NICU RN so I am competent with medical terminology. I do take care of newborns with hemolytic anemia, but most of them have ABO incompatibility and easily treatable if caught early enough (phototherapy, IV fluids, exchange transfusion, IVIG). I never knew that dogs and cats could have a similar disease (but MUCH harder to treat).

Since my first post I mentioned Pickles got transfused again with 2 units of pRBCs on 11/29. Its been 2 weeks and his HCT/PCV is holding up at about 30, which is the highest average he’s been since he was diagnosed 1 month ago. His reticulocytes were at 101k before the transfusion (his PCV was 12) and now its down to 36k. I’m not sure if this is because he got loaded with blood and his body thinks a PCV of 30 is high enough since he had been used to being so low? I see this similar response happen to human babies after a transfusion. We also did a set of total body function labs on 12/10 and his liver enzymes were quite elevated (AST 38, ALT 313, GGT 144). I did switch him to denamarin on 12/1, so I’m hoping it will help slow down the liver damage.

We got referred to another internist here in LA and she’s dealt with many IMHA and ITP cases throughout her 30+ year career. She wasn’t surprised with the ALT being a little high, but she was a bit baffled at the GGT being WAY high. She said its usually a sign of cholestasis, except his bilirubin is normal (0.3) so cholestasis doesn’t seem likely. I may consult with Dr. Dodds about this if his liver enzymes keep trending up. His internist also doesn’t recommend weaning or changing any of his meds right now (pred, myco, cyclo) until his PCV is stable for a month.

I also asked if we could do vitamin B12 shots, and my vet agreed. So I will be giving them weekly (started on 12/10). Because of his elevated liver enzymes, I did switch him to the low fat liver support diet from Dr. Dodd’s website. But the cod gave him diarrhea (he’s never had fish diet before) so I am still mixing it with half lamb/rice (Just Food For Dogs). He’s lost about 7lbs since we started all the meds, so I am feeding him 4x/day…

Otherwise Pickles is happy and has quite a bit of energy now. This is the longest he has gone without a transfusion, so I am praying that the meds are starting to work and we can wean soon.

I think thats all the updates I have for now….we have another appt with the vet on 12/18.

Thanks again for your support!

Pickles and Allison.

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