Page 5 – Second Chance AIHA Dogs

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Keymaster

I am sorry to read about Shadow.

Evans Syndrome is a complex autoimmune condition that may lead to autoimmune hemolytic anemia, immune-mediated thrombocytopenia (ITP) and neutropenia. Each of these conditions are serious and combined together can be challenging to treat.

Hearing loss, at least as much I can research, is not directly related to these conditions normally. But that does not rule them out as an indirect cause.

Since I’ve never talked with an owner reporting this I can draw some conclusions from some of the effects that these diseases can contribute to.

Anemia is a reduced level of oxygen being delivered to body cells. In this case it is due to an extreme loss of red blood cells. Many dogs with extremely low hematocrit/PCV can develop heart symptoms due to low levels of oxygen. Vets do report, esp in small dogs, a noticeable heart murmur. If they recover from IMHA, they may or may not continue to have small murmurs. So from this knowledge I can imagine that loss of oxygen to the delicate inner ear structures might also lead to some tissue death. I’m guessing this is the most likely cause.

But also, looking at the ITP, which is an extreme loss of platelets, I can also see a possible connection. These cells are responsible for important clotting inside the blood vessels. We have tiny damage to our vessels normally all the time. Platelets are very active in protecting and repairing that damage. With low platelets the body gets confused and attempts to provide clotting but ends up doing in many of the wrong places. This can lead to small clots in inappropriate places. If this occurs rapidly all at once, there is a risk of death. But in your case there may have been small abnormal clots in the small delicate vessels of the inner ear. Kind of like a little stroke.

Finally, neutropenia is a low or lack of production of white blood cells in the body. This leaves a dog susceptible to all kinds if opportunistic infections. This is a very serious risk. Perhaps Shadow developed an inner ear infection that partially damaged tissue.

Some antibiotics can lead to allergic reactions so I also see a possible connection to an inflammatory reaction in the inner ear.

These are my best guess suggestions. Please take what I say as guesswork, not a diagnosis.

Regardless, I think that there is partial damage to the delicate inner ear structures.

You might try adding antioxidant supplements to reduce free radicals in the body. Aim to provide a highly nutritious diet. There is some truth that the body can heal itself. Provide extras like small amounts of liver, eggs, yogurt, blueberries, canned plain pumpkin. I give my dogs those foods on a regular basis. Be sure that the rest of the diet contains high quality protein, moderate to low fat and leave out things like grains, rice and other similar foods that dogs can have allergies to. I do not recommend grain free designer dog kibbles. There has been scrutiny recently about their possible connection to heart problems. I am not sure this is true, but in your case just avoid them. If you are up to it the best diet you can feed is homemade. There are several excellent Facebook groups that help you with that.

None of us who have gone through these terrible autoimmune diseases gets exactly the same dog back that we went into these diseases with. They are a bit more fragile and we tend to be more cautious. That you beat this particularly complex condition is a testament to your great dedication to Shadow and his strong will to live. You’ve done a super job. The hearing difficulty is a badge of honor to a warrior that survived a terrible disease. Enjoy the extra time you have earned.
My best Patrice

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Patrice

Keymaster

Francesca,
I am sorry to read this about Zhenya, it can be frightening when this happens so suddenly.

In the past, many vets believed that AIHA (as it was called for years) was a primary condition, or there was no cause. They felt that the body just began “attacking self” without cause.

Now we know much more about this condition and it is referred to as IMHA, immune mediated hemolytic anemia. It means that there have been contributing triggers that “mediate” or cause something to happen to the immune sysrem. Hemolytic means destruction of a red blood cell. Anemia specifically means a condition of low hemoglobin and therefore there is less oxygen going to body cells.

Now we understand that there can be many triggers to cause IMHA. There are usually several triggers that interact and lead to a cascade of events. The main triggers that are generally recognized are genetic predisposition. This is usually breed dependant, there are breeds that have more cases of IMHA than otheres. These breeds may in general have more autoimmune conditions like allergies, gastro-intestinal conditions like frequent diarrhea, colitis, SIBO. The genetics of breeds in general can show DNA defects due to short lifespans and a faster metabolism.

So it is doubtful that this happened in just a few days. There were single triggers that went unnoticed until there was a combined tipping point. It wasn’t something you did wrong, it can be hard to see the signs.

What are some other triggers along with breed predisposition? Other big contributors are recent vaccines, tick bites, sex hormones, stress (this can be environmental such as allergies), or it can be infections, viruses. Another complex cause can be tumors. Even something like a bee sting or snake bite can lead to a tipping of the autoimmune system. Any vet facing this condition really needs to do a complete history looking for every trigger, and especially those that can be treated. For instance tick disease can be tested for and if positive, treatment is high dose Doxycycline. In this way the IMHA cause is treated.

So we need to make sure all the detective work has been done so your vet can treat anything contibuting.

So I looked over the CBC and I see he was first diagnosed with a HCT of about 17%. He was also highly regenerative (making plenty of new baby blood cells) at this time. This is a positive sign. The new baby cells are called reticulocytes. In about 3-4 days after they show up in the blood they mature and become RBC.

I see that this week he has a HCT of about 31%. This is an excellent recovery. The goal to reach that is considered the low normal value is around 36-38%. But I also see that the reticulocytes are slowing down. It would be better if this regenerative state continued until he reached normal values.

So I also see that he has had very high white blood cell counts in several lines. The monocytes are in the greatest number but there are other WBC that are abnormally high. This inflammatory state can definitely cause a condition called anemia of chronic disease. The body attempts to shut down or restrict the body’s resources that supply bacteria or viruses with nutrition and blood supply. But that also can reduce the body’s ability to make blood cells.

We see that the values of monocytes have dropped considerably from over 51 K/ul to about 33K/ul this week. So if there is an infection we would want to know what it is. But the decrease is in direct relationship to the increase in hematocrit (greater number of RBC.)

Sometimes allergic conditions can lead to an inflammatory reaction. So perhaps parasites like worms, or atopic allergies (inhaled allergens ).

You are giving 2 immuno-suppressant drugs, prednisone and the Italian version of our azathioprine in the USA. The prednisone suppresses the whole immune system. In the acute stage this is absolutely a life saver. But long-term use affects just about every body organ an system. You’ve been seeing this sad change in his body. The muscle wasting is expected, the constant drinking and peeing, the weakness, shifting fat makes his belly look dumpy. Some dogs get a wasted head, the bones become prominent.

I suspect that despite the use of antacids he may have developed a stomach ulcer, thus the poor appetite. There might even be some degree of pancreatitis, another common side effect from prednisone. So let’s put him on a drug that will heal any possible ulcers. Sucralfate is a mucous like bandaid for the esophagus and stomach. Your vet must provide you with this or a prescription. But it’s commonly used in humans and is very safe. Be sure to give it away from food or medication as it will cause them to be poorly absorbed. I like to use it on an overnight fast.

Next, ask your vet to do a specific IDEXX test for pancreatitis called cPLI, canine Pancreatic Lipase. This is extremely accurate. If the value is positive then you will need to provide a very low fat diet, and smaller more frequent meals. Attempt to feed just enough calories to get to the next meal. This will help the inflamed pancreas to rest and heal. Dogs can recover from singular episodes of pancreatitis but do much poorly when it becomes chronic. So best to treat it correctly and quickly.

I know how hard all this sounds to you right now. We truly believe here on Second Chance that excellent home care by Mom the nurse is critical to successfully treat this condition.

Keep a positive relationship with your vet, ask questions and expect to be treated as an equal part of the team that provides care.

Any of the hard stuff you don’t understand, lean on us. It’s hard to make complex decisions when you don’t know all the details. We want you to make decisions based on facts not emotions. That way you will know, at each step, that you have done the best you can.

We both have been through this and we know how sad and frightening it can be. But we have also seen hundreds of dogs survive. We know it is possible.

What other questions do you have?
My best Patrice

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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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Patrice

Keymaster

Amy,
Yes it has to do with proper absorption. Cyclosporin is a derivative of a fungus. To manufacture it properly it has to be carefully stabilized and purified then enhanced with “helpers” to ensure it is completely absorbed. Food and other medications can disrupt the biochemical reaction.

Cyclosporin (brand Atopica) went through stringent testing on dogs to determine the best effective doses, the action and the results. Then they evaluated the drug for negative side effects, including extreme doses.

The results showed that dogs tolerate this drug very well. It is very effective in targeting the t-cell lymphocytes that are the main activator of the immune system against red blood cells while leaving other elements of the immune system unaffected. This is unlike prednisone which overwhelmingly affects the entire immune system.

In terms of side effects they are limited at normal doses and are usually only gastrointestinal: diarrhea, stomach upset and vomiting. After a few days dogs generally adjust and have no problems. Lowering the dose or giving it with food in the early days helps to improve adjustment.

If side effects are more serious the drug can be stopped and side effects will go away quickly.

I contacted the manufacturer about the common practice of freezing the capsules to make it less bothersome to dogs. In fact it destroys the drug inside the carefully manufactured capsules. No wonder it doesn’t cause side effects, the capsules are ruined and the drug has lost its potency. Each capsule can be $2-3 so I am not sure why vets recommend this practice.

I prefer to see a dog take it with a little snack or at a reduced dose for a few days so they can adjust. This drug is extremely effective in treating dogs with autoimmune conditions, and is also used inhuman medicine.

In fact it was originally developed many years ago for use in patients with heart transplants. It was extremely successful and now is a standard drug.

I’m sorry about the upset gi tract. It can be the cyclo but the cellcept is a much worse bad actor when it comes to GI tract side effects.

So try a little snack about 2 hours before meals, no calcium or fats. A soft dog cookie might be enough.

At high doses some dogs (and humans) can have a side effect of feeling “spacey” but it doesn’t seem to be harmful. Chance would lie very still and stare off in the distance. After an hour or so he would be ok.
My best Patrice

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