First, let me qualify this guide. In its current state it is a document in progress and has been written solely from my own experience with Dog Dylan and discussion groups I have been involved in since she was diagnosed. I would like any comments, additions, suggestions etc. There is still a lot to be added in areas that impact others in which my Dog Dylan had no experience. This is important for you to remember when reading, as there may be huge gaps when it comes to other situations. This is a first draft and it is no where near complete, I just chose to get some info out now and write it live. It is a living document. I hope that with comments and suggestions it can become a more well-rounded and informative document.
And most importantly! I am not a Veterinarian!
Please consult your Veterinarian regarding anything written here, prior to doing anything.
Although I am certainly not a vet and I am certainly not qualified to diagnose problems such as IMHA/AIHA, I do have 15 years of post secondary education including a B.Sc. (Honours) in Psychology and 3 years of post graduate study at the University of Calgary in Psychology (M.Sc.) with a focus on behavior , physiology, pharmacology and neuroscience. I also have 6 years of post graduate work as a scientist at the University of British Columbia in Neuroscience also focusing on behavior, physiology, pharmacology and neuroscience.
I am an expert at learning on my own (as must be the case for a scientist) and have spent all of my life learning. I am also a critical thinker and I do not accept either dogma, or propaganda as sufficient for me to believe in something. It is my very strong belief that current practices are at least 20 years behind current knowledge. This is my experience with science, with Crohn’s disease and almost every subject surrounding the best health care for my dogs.
In addition, I have spent most of the last 20+ years dealing closely with Crohn’s disease, which is an autoimmune disorder in people. I am very familiar with prednisone, the immunosuppressants and antibiotics used to treat autoimmune diseases, including some experience with their use in clinical trials for Crohn’s disease.
Currently my expertise includes canine behavior with a crash course in IMHA/AIHA. My education experience along with my experience with Crohn’s disease and my knowledge of Canine behavior was invaluable in assisting Dylan and the choices I made for her survival. I have worked very closely with Dylan’s vets and due to my ability to see what is happening in Dylan, have been given a lot of freedom to determine Dylan’s treatment. Of course with their consultation and support, as it should be. This included the decision to use less prednisone during her second attack and each and every prednisone dose reduction during that attack and also during the initial attack. During both attacks, analysis of Dylan’s behavior was a significant component of removing the prednisone being used to treat the disease.
Also, there is a significant contribution to my knowledge from those others I know who support people and dogs fighting this disease. Knowledge and experience from a variety of support groups ins included within this document and I certainly hope to include a lot more. I also intend to try and provide scientific references as well within this document, but that will likely be following the experience related material.
Since there are different types of anemia, I should probably start by describing how a dog’s become anemic in Autoimmune Hemolytic Anemia (AIHA) and Immune Mediated Hemolytic Anemia (IMHA) which are the primary causes of anemia in dogs. For the purpose of this discussion, AIHA is considered a specific form of IMHA, or it can be considered as separate from IMHA (since we don’t really know). I have also read that IMHA is just a newer and less specific term. However, the exact truth is not as important as maybe a consideration of the different ways AIHA/IMHA is triggered and the actual symptoms and disease progression.
Autoimmune Hemolytic Anemia (AIHA)
AIHA is where the immune attack is on mature red blood cells and the cause is known as idiopathic, that is of unknown, or no determinable cause. Generally AIHA is thought to be a failure of the immune system which results in mistakenly attacking otherwise normal Red Blood Cells. It kills mature RBC’s. Often this is accompanied by loss of appetite, vomiting, pale gums, brown patches in the gums and whites of the eyes, orange/brown/dark red pee, orange stool and possibly blood in the stool.
I have also learned with Dylan’s second attack, that I could see other signs a day or two earlier. Depending on the dog, lethargy may or may not be a good indicator. Dylan is a pretty lazy dog in general and so a little anemia is not always easy to see. But the obvious contradiction in this was that for 2 mornings she got up very early to pee, which was very uncharacteristic of her, as she normally sleeps in until the food comes out.
This was also followed by increased need to drink water. Excess peeing and increased drinking is a bad sign and is indicative of the blood cells being attacked and the kidneys excreting protein and other byproducts of this breakdown. Through osmosis, water is drawn through the kidneys, creating more urine and an increased need to pee and therefore dehydration and a need to drink excessively; something I noted, but was unsure of its significance. I am no longer unsure, as the next sign was the loss of apatite that was my first sign during the first attack.Later that day I did see red pee again.
I am now ready to act based on urination schedule and dehydration/drinking and believe I can stop the attack at least 24 hours sooner by getting prednisone into Dylan 24 – 48 hours sooner. As it was her PCV was 4% higher when the attack was detected during this second attack. I plan to stop it faster if there is a next time.
Immune Mediated Hemolytic Anemia (IMHA)
IMHA on the other hand is thought to be a result of some toxin, which may remain present, or not, but in both cases alters protein structure in the membranes of specific cells. These then modified proteins are seen as foreign by the immune system. My opinion on this is that the above may or may not be true and we have no firm evidence either way, other than the fact that in some cases there is clearly a toxic trigger such as from a tick, chemical ingested, toxic metal, vaccine, etc. which would define the cases as IMHA, not AIHA, but that the lack of a known trigger does not firmly define anything. So a functional definition as is above is fine for me.
Dogs, like all animals, become anemic when either Red Blood Cell numbers fall, or their contents change in such a way as to lower their oxygen carrying capacity, or both. In the case of AIHA/IMHA we are strictly dealing with anemia as a direct result of the number of RBC’s carrying oxygen.
One way to reduce RBC numbers is when RBC’s caring oxygen are destroyed causing their numbers to fall and oxygen carrying capacity to fall according to the rate they are destroyed. Red blood cells do have a limited life span and they die naturally as well, so the body continually builds new RBC’s to replace them dependent on the rate they are needed. During an attack, that need will rise and production of new ones will be seen first as an increase in the number of immature cells, reticulocytes, then increasing numbers of new RBC’s and thus increased oxygen carrying capacity. During anemia, initially the rate of replacement will be low and will need time to catch up. In regenerative anemia, you will see the the increase in blood tests and if the attack is suppressed, the PCV and hematocrit along with RBC numbers, hemoglobin will all rise. You will also see the changes in behavior as their oxygen carrying capacity returns.
Anemia can also be caused by failures to produce new cells. New RBC’s along with other blood cell types are produced in the bone marrow and are release into the blood stream. If there is any failure to produce new cells, dogs will become anemic. This can be slow and minor due maybe to an imbalance in the body, or lack of nutrients, or it can be serious or complete failure as in the case of IMHA. Depending on what stage of development that is attacked in the case of IMHA, you might see just RBC’s impacted, or you might also see platelets reduced, which is somewhat common, and also White Blood Cells (WBC). This is because these cells all have a common initial development and as they differentiate have less in common. The profile of cell loss can indicate where in the development cycle the attack is occurring.
Recovery from Anemia
In non-regenerative anemia, the time it takes to see positive changes as a result of treatment or negative changes as a result of an attack are likely more prolonged. Not only do you have to stop the attack, which might be harder if it is in the bone marrow, the process of building new RBC’s takes longer as they have to start from scratch. The full development cycle may be required. In regenerative anemia, the loss of cells triggers an immediate production, raising the level of immature reticulocytes. If the attack is ongoing, depending on the intensity of the attack, this could result in low RBC related levels only, or in the case of an aggressive acute attack, the RBC values; PCV, hematocrit, RBC’s, hemoglobin, all continue to fall. Once the attack is suppressed, however, the time to recovery can be short as the body has already ramped up reticulocyte production so there is an increased supply chain of new cells, with a shorter development cycle to complete.
Symptoms and Progression
So in AIHA and possibly in IMHA as well, although not necessarily (non-regenerative), you see the destruction of RBC’s and very often other signs in addition to anemia that accompany this. Due to the nature of destroying RBC’s, protein and other contents spill over into the kidneys and other organs. This damage may occur in the blood vessels, as was the case with Dylan, or it may also be occurring in other areas of the body. In addition to the dehydration it causes with increased need to pee (I will always be looking for this in Dylan), orange or dark brown/red pee, buildup of RBC brekdown byproducts that can be seen in the gums and whites of the eyes as dark brown, or yellowish patches; loss of appetite, vomiting and orange or dark areas or spots in their stool. This may also be seen in other forms of regenerative IMHA if whatever toxin is incorporated into mature RBC’s. Other than the fact that a specific toxin was known to be the cause, there is nothing else that would differentiate AIHA from IMHA in this case.
Non-regenerative anemia will not show the other physical signs, or it may display as loss of protein but not necessarily RBC type debris, no spherocytes, no iron or hemoglobin to make the dark color you see with mature RBC destruction. You might still see protein loss and dehydration that results however, but this will require a full CBC blood test to determine. Blood test will also be required to determine at what level the attack is occurring. Often non-regenerative anemia induced by toxin and subsequent immune attack of IMHA is interpreted as bone marrow failure for other reasons that include cancer, leukemia, etc. Often this is not the case and aggressive treatment of the immune system results in bone marrow function returning and production of the various cell types that the IMHA attack had impacted. Because of this, it is important to note that any treatment changes, positive, or negative will have longer timelines before becoming visible in behavior. These are very important differences when treating AIHA/IMHA initially and throughout treatment, especially when removing drugs during recovery.
Treatment of AIHA/IMHA
Treatment varies and includes glucocorticoids like prednisone and prednisolone to suppress the immune system quickly and immunosuppressant drugs like Azathioprine, Cyclosporine, Methotrexate, etc. (of which the most common are cyclosporine (faster effect) and azathioprine usually in combination with prednisone for quicker and/or more certain immune suppression. Often added is an antibiotic and it can be for good reason, since for example tick induced failure can be treated with specific antibiotics. It seems that there is no 100% certain scenario for treatment in AIHA or IMHA as for which drugs work for which dogs and which cases. Generally in North America it will be treated with a cocktail of the above, although this is not always the case, as was so for Dylan.
Slightly off topic, but worth noting, antibiotics and other treatment options are often required for secondary reasons as there are plenty of other problems, most commonly infections and clotting issues. During treatment, stomach protectants like Famotidyne (Pepcid AC) and Sucralfate are used to prevent ulcers caused by medication and Milk Thistle or substances like Denamarin are used to aid the liver though this challenging time as well.
Dogs treated for AIHA/IMHA, due to the immune suppression that is required in the treatment for stopping the attack, all dogs are initially immune compromised during their treatment. The initial levels of prednisone and also the immunosuppressants are fully intended to shutdown the immune system, which is absolutely required to stop the attack. Especially when used in combinations at high levels as is often the case and as is often required, many other complications from side effects of treatment can result. Infections are common, so use of antibiotics is also common. There are complications from all of the drugs used to treat IMHA/AIHA.
It is also important to note, that although dosing standards are given by weight, this is not always the best and only consideration. All drugs have a minimum level required to achieve the desired effect. For example, prednisone at low doses does not stop immune function, but functions in an anti-inflammatory role. At higher levels it functions to suppress immune function. And the fact is there is an upper limit to this function, or efficacy as it is referred to, where it actually begins to suppress the creation of RBC”s and other blood cells as well.
And in the case of prednisone at least, if is very possible for some dogs to be much more reactive to the hormone and thus resulting in serious consequences quickly. Early symptoms of prednisone use include excess drinking, excess peeing, panting, increased appetite, and aggression. More serious symptoms of prednisone induced, iatrogenic Cushings Disease include skin problems of a variety of kinds, infections, hind end paralysis, muscle loss, lesions and ulcers and can get more serious and include bone loss and serious arthritis as a result.
Unlike most dogs who seem to be able to handle the high doses used, 2 mg/ pound/ day to some degree, Dylan could not and I saw serious muscle loss immediately and hind end paralysis within 3 weeks to where Dylan was unable to lift her head to eat or drink within 5 weeks. I think it is important to gauge the effects of prednisone throughout treatment for this excess reactivity. as a result, during her second attack, I used much lower doses of prednisone and it stopped the attack 2 days faster (2 instead of 4). There is an upper limit to effectiveness! More is not always better! Some individuals are more sensitive than others. Individuality matters in my opinion and I believe customization of treatment to the individual is essential.
This also occurs in reverse, however , and some dogs require higher doses. Maybe this is why the average dose suggested has gone fro m 1 mg/ pound/ per day to 2mg/lb/day. I see this trend elsewhere and I think it can be worrying in some dogs. I do know several dogs who have crashed due to high levels and chronic toxicity. There can be kidney and liver infections and other issues and constant monitoring is required, especially when combined with immunosppressants like azathioprin or cyclosporine. The factis, that it can be tough to know. One pattern I am aware of is that in some cases there is a quick recovery of PCV. If this is followed by gradual or sudden decrease in PCV, then I would look at causes that includes drug toxicity, side effects and maybe infection, but I would certainly suspect the drugs as potentially involved.
on the other hand, delayed and slow recovery is also observed and this is more difficult to determine. More often than not, time is required, as delayed recovery is often an issue with bone marrow function, rather than immune function. In most cases I have seen, drug levels are increased. On occasion, I hae seen them decreased to be more effective. we also have seen reactions to drugs like cyclosporine, but sometimes simple tricks help, like taking a little milk with cyclosporine has been known to help tolerate it without vomiting.
In several cases, however, I have also seen dogs suddenly lose the ability to battle the drugs along with the disease. When his occurs, infections and other issues begin to win and the PCV and other factors can suddenly fall. Organs can be in trouble, clotting, ulcers and other things can occur. Tough to say in these case if you can get the drugs out fast enough, because if the disease is still present, it becomes a no win situation. at best it is a very delicate balance.
Also worth noting is that the dog is never really stable. There body is in a constant fight. They fluctuate between better times and worse times. It is tough for the body to find balance as it struggles to deal with the disease and the drugs used to treat it. This is an extremely stressful situation and it is my opinion dogs should get as much rest as possible and as little activity as possible to conserve energy always for their internal fight.
Another very important consideration is their diet. they need a very healthy diet to provide all the resources they need. During the initial breakdown, before the attack is stopped, contents of RBC’s and the drugs used for treatment are putting great stress on the lover and other organs and in the case of liver trouble, a liver sparing diet may be recommended. It is my opinion as well that if the dog is healthy enough, a well balanced diet is required. Cooked human food is often recommended as a better source of nutrient and easier on the lover, provided the diet follows the proper guidelines
More on diet to come!
Anemia and Behavior
In a normal dog that is becoming anemic and not yet on any drugs, the change can occur overnight and result in some very different early morning behavior or even after a long sleep during the day. If it is due to AIHA in particular (maybe regenerative IMHA too), you will likely see other signs as mentioned above, but the anemia can progress over a period of hours, days, weeks and even over months. Fast progression is often easier to diagnose. Slow progression is often misdiagnosed. Sudden AIHA seems to be pretty easy to diagnose and non-regenerative IMHA the hardest. Cause of the problem can certainly determine treatment in the case of the latter.
Although Dylan’s attacks were sudden, they were hard to see the initial signs, since Dylan is older and generally less active. She loves her walks and gets very excited for food, but she can go long periods just sleeping. So other than the other behavioral signs that accompany her anemia, pure tiredness is not my first sign and if it were I might not catch it soon enough. The most obvious sign was her hesitation to eat as she obviously felt ill. Often other signs that come early would be decreased tendency to play, more likely to follow you and stay close to you. They may not be enthusiastic to get up, or go outside. Any change is important. Anemia is often seen as lazy by people, or attitude. This is simply not the case and they are likely just tired and not feeling well. I know my dogs get depressed when they feel ill as they know they are not going to play. And if a dog who normally feels like playing does not, something is wrong.
Always trust changes in behavior, especially for things they enjoy. Hesitation to eat for a dog that devours its meal normally and consistently is cause for concern. Apparently even if my dog Dylan gets up early for a pee and drinks excessively after is a cause for serious concern, s this is the start of an AIHA attack. Something I learned during the second attack. Reasons for changes can be many from injury to illness, but when it comes to things they enjoy, it is never “attitude” or “laziness.” Changes always have a foundation in real underlying cause and you should immediately seek out what the cause might be. Maybe it is minor, but if it is (or even if not), the sooner you see the cause, or know that a problem really does exist, the greater likelihood you have of doing something successful about it.
As anemia increases and gets serious you will see more than just tiredness. Likely you will notice that the position of their head is held lower and likely the ears will be lower, often drooping to the side as well. Their eyes will look tired and their tail won’t wiggle, or if it does, it will be with reduced effort. When they walk, it will not be quickly and in fact will likely appear very deliberate and cautious at some point. They tend to lose the skip the often have in their step. You won’t see them shake their head and body much either as they get weaker.
They will likely pause on occasion when doing something, walking, getting up, etc. and wait for their strength or head to clear. I have seen panic attacks, or syncope, that is fainting and blackouts. These can occur following many things including getting excited for food or a visitor, or even a bowel movement for that matter. In AIHA and IMHA they may be often be dehydrated and losing protein, which also adds to hypotension, producing increased likelihood of blackouts.
At low PCV/RBC levels, following a bowel movement will be the most obvious time you see this. If they did not pee first, they will likely do so when they blackout. I became fully aware of this in Dylan at her low points this time. Somewhere between 5 and 10 seconds following her poop, she would pause, get stiff and freeze in place. She would lose her balance and during the first attack of AIHA, failed to get up as she had already laid down. I would see her muscles tense in fear as she was losing consciousness and found that if I knew to expect it, I could be there to hold her through it so she did not hurt herself and could be reassured and less fearful.
One of the most obvious tests to do is the gum test, although I don’t find I personally learn as much as from watching their behavior and judging their RBC levels that way. Gums will generally be pale, but the gum test is when you press the gums and watch for the blood to return. The more anemic they are the longer it will take the pink to return. If you test their gums often, you can gauge their level of anemia from your experience. This is similar to what I do with behavior. The tongue itself is not a good indicator of mild or moderate anemia, but when anemia is very serious or critical; their tongue tells you a lot.
Behavior shows a progression of loss throughout an attack which causes anemia. As the anemia worsens they will lose stability in standing and walking. Balance will become an issue. They will probably stop going up on chairs and couches even if allowed as they begin to lose balance. They may still try and falter as well. Things that were simple become difficult and are avoided. Trial and failure can be stressful and provoke anxiety.
As it worsens, they will walk as though they are drunk and not walk in a straight line. On uneven surfaces they may falter and catch themselves or fall as it gets worse. This will start to happen on even and normal indoor surfaces too. As anemia increases their tongue does get weaker too and the curl they use for drinking is not so strong. This often means much more effort to drink is required and it takes longer to consume water. It can also be accompanied by choking on water occasionally as they are unable to get water in effectively.
As the get weaker, they do not have the strength to make every step and they may put pressure on their feet without being able to place the pads down. The may be unable to bring their legs far enough forward or have strength to pull their feat up before putting weight on them. This may cause them to fall as well. The movement of their limbs and feat become spaghetti like, clearly lacking strength, often exaggerated movements in an attempt to achieve very basic functions that were once so easy.
During the most severe anemia they will not have the strength to get up or lift their body for water or to even go outside to pee, or for a bowel movement. This may cause them to panic, or experience anxiety and anxiety attacks so calming them and reassuring them is important. Recognizing panic attacks and their fear induced actions, as was so with Dylan, becomes important. It is important that you recognize they may be confused and light headed and to adjust your actions. Maybe they need physical support, or just reassurance. Maybe they need to be held carefully. Patience may be required. At this point there is little choice.
Anemia at Rest
When lying down, sleeping, I watch their breathing. Normal breathing will get shallow and less frequent during deep sleep. During REM sleep they will get active and breathing will be frequent and deeper and often accompanied by physical sounds and actions, including rapid eye movements. If they were running and jumping, you will likely see running and jumping, maybe chirping and barking too. You might see a few short cycles of REM and then back to sleep where they go into deep sleep again. Like us, this cycle is about 2-3 hours depending on age and other factors.
When anemic, they lose much if not all the excited, REM type sleep. They may maintain some, but it will be obviously reduced in intensity, to non-existent. This probably won’t be noticeable for mild anemia, but for higher levels what you will likely still see is periods of very relaxed breathing, with lower respiratory rates and shallower breaths. This can become quite shallow and slow and during severe anemia can result in brain damage as a result of ischemic cell death, that is death due to lack of oxygen.
Respiration can get labored and stressed in other types of breathing problems and low oxygen situations, but this is not usually seen in AIHA/IMHA. They usually lack the energy and muscle output is the same as their input – low – so they become extremely tired rather than stressed! I have not seen gasping for air like I might see if the heart were being compressed by a tumor, or fluid pressure.
The Question of Transfusions
When or if to do a transfusion is up to the individual really and likely varies greatly as to when one would choose to do one. When anemia is very serious they are less likely to be successful. I am not one to want to do transfusions too soon, but I think many vets and emergency clinics will do them at PCV’s close to 20, but during both of Dylan’s attacks we did not do transfusions. During her first attack, after being diagnosed with a PCV of .20, her PCV sank to the minimum possible, maybe as low as .07, or .08 before recovering in 10 days to .39. During her second attack we caught it sooner, PCV .24, and treatment worked faster so she never got below about .17. These values are actually not measured, but estimated based on the behavioral symptoms I saw. In each case though I would never have considered her condition serious enough until it got closer to 15. I think around 14-15 is most common, but again, I would want to wait a little longer. I can’t imagine having done one for Dylan anywhere near 20 as she was still far too strong and had far too much ability to recover on her own as she did. Even at 14, or 15 she was still pretty capable.
Because demonstration of behavioral symptoms does not always correlate to measured PCV values, I am more likely to rely on behavior to determine my dog’s health, whereas most others I know go for PCV tests even as often as daily. I am not sure the constant trips to the vet are a good thing for the emotional state of a dog, so please consider the effects of emotional stress in your decision. Of course the actual symptoms and state will must determine what is done and not what is written here. Some situations are a lot tougher to read , or there may be significant complicating factors; there may be other cell types in a dangerous state, like platelets as well. This of course will impact any decision to do transfusions, as there is a significant danger of a transfusion going badly once platelet levels get too low for clotting to occur.
Also, whether a dog is regenerative, or non-regenerative makes a big difference. Transfusions buy time, especially with non-regenerative anemia, where the issue may be in the bone marrow and stopping the disease and stimulating th bone marrow to produce new blood cells may require more time. Although following transfusions, PCV may rise, this does not mean they are doing better. They must produce RBC’s on their own. I have also seen several cases where the PCV did not rise after transfusions, however, it did not fall either.
For the most part I have also not observed any issues really following transfusions. Although they never solve the problems a dog is facing, I have not seen them contribute to the death of a dog, as I have with the chemicals used to treat the disease. This was something I was concerned about during her first attack, but as I said, for dog’s that have time, or that you know their blood type, this is a valuable option. For Dylan though, her attack was sudden, and when her condition deteriorated unexpectedly and also included a daily cycle, I was unsure of the ability to type her and match her blood in a very weak state and risks increased quickly of further issues.
Whether I Was doing a transfusion or not, I would probably want the blood type matched in order to be prepared for that option later if necessary.
Dylan was treated using high dose prednisone alone in both AIHA attacks. During the first attack she was treated with just over 2 mg/pound/day (split in 2x 50mg doses) and it took close to 4 days for prednisone to completely stop the attack with her anemia bottoming out as she became critical. At that point she could not walk or consume water on her own. During the second attack, due to her serious reactivity to prednisone during her first treatment, she was treated with less than 1mg/pound/day (split in 2x 20mg doses) and in less than 2 days her attack was completely halted, sparing her from severe anemia. I fortunately caught the attack earlier in the progression of the attack (PCV .24 instead of .20) and with a lower dose was able to stop the attack well before she progressed beyond being unstable while walking. She never fell down and never had any serious issues from the anemia.
Prednisone and Behavior
How prednisone treatment impacts your dog’s behavior is also important in judging anemia since it has direct effects on some of the behaviors you might see in an anemic dog. Prednisone stimulates metabolic activity, burning calories and generating heat. To maintain body temperature, they must express heat and as a result must pant. Prednisone, therefore, induces more rapid and deeper breathing and panting. This can be seen during sleeping at any stage and can include panting or not. They appear hot and actually they are trying to get rid of excess heat generated by excess metabolism induced by the prednisone. Although this is similar, it is a very active process and not at all like anemia where everything is slow and calm. When they are anemic it is a bit of a “catch 22” as they are burning calories they need with limited amounts of oxygen. This leaves even less energy available for activity. When on lower doses of prednisone and when experiencing lower reactivity, these effects may be less severe or minimal, but likely still influence day to day activity levels along with the fact that they feel ill.
In fact, even as dogs recover from anemia once immunosuppression has occurred, they will appear tired and not necessarily return to normal as quickly while still on prednisone. While on high dose prednisone, it is equivalent to sprinting while lying in their bed, constantly burning calories while they rest. Depending on their individual reactivity and the dosage given, this will likely leave them far less energy to use than normal and combined with the fact that they are still ill and feeling abnormal, will likely still seem lethargic.
Behavior: Treatment and Recovery
As they recover oxygen carrying capacity and strength, while on prednisone, I monitor their behavior during the activities that make them excited. Behavior lost will likely reappear in the reverse order it was lost as well. Since prednisone increases food drive and can increase aggression, these are signs I look for to make sure prednisone is working and to see how much strength and stamina they have during exciting times like feeding time. As their strength increases they will spend more time out and on their feet. You can see the skip in their step return as they gain strength and stamina and begin to feel better and become more confident again. They will actively follow and steal food from people, even fight for food with other dogs. When they are seriously anemic, before prednisone induced suppression, they will not have energy to follow and be aggressive for food, so this is a sign of recovery.
Blackouts if they were occurring will stop and are an easy thing to look for. I saw them originally during bowel movements and even early in Dylan’s recovery when she would get excited to greet a friend at the door. Earlier when strictly anemic, she would not get excited at all. So the fat that she got excited was as sign of recovery, but the syncope showed she had not recovered much yet. When those episodes disappeared I knew she had recovered further. As recovery occurs, things like stability while drinking and walking improve. I often test this while Dylan is standing. As they continue to improve, getting back on couches, that wonderful wiggling tail, ears and head go up as everything is reversed.
The improvements in behavior are a clear sign oxygen carrying capacity is improving; reticulocytes are being produced and are maturing into RBC’s. There is no other way to improve from anemia, aside from a transfusion. You will see the same improvement from a transfusion, but since the change in RBCs is not created by the dog’s own body, there will likely be a decline following the transfusion, until the dog’s own body begins producing reticulocytes and RBCs. Then recovery will occur.
So at some point during treatment, either like in Dylan right away, or with other dogs after some period of prolonged treatment it will become necessary to remove prednisone and other drugs. With prednisone alone, it is much clearer regarding what you will see since there are no interactions or other substances also inhibiting the immune system. I have already defined what one should expect if anemia is reduced and if any drug is removed that is responsible for suppressing the immune system and the attack is still underway, or the disease is still active, then anemia will increase although one would expect differences between non-regenerative and regenerative types of anemia in what to expect.
Prednisone reductions might be performed just to get to a lower dose even while the attack is underway, or they might be performed after it is thought the attack has ceased, but likely they will be performed without knowing the answer so careful observation is required. There is no way to know if the disease is gone and the attack has ceased until you try. How long this takes varies in every case, but generally there is no systematic attempt to determine if it is gone nor is there any clear indicator that it is. Generally my first reductions are to get my dog to the lowest dose that still provides immune suppression and stabilize her there. She is so reactive to prednisone that the side effects are quick to occur and severe so avoiding them is the only option. It is my opinion that any treatment should seek to first stop the disease, then minimize impact of the drugs used to treat it, then get rid of the drugs used for treatment when and where possible and as soon as possible. I see all of these drugs as having serious and harmful side effects that are worse at higher doses, when maintained for long periods of time and present in combination with other toxic drugs used for treatment.
Watching Prednisone in Action: Side Effects and Efficacy
During prednisone reductions, just like when watching for recovery, I don’t watch their rest state as much for anemia as I do for the influence of prednisone. Seeing how fast they are breathing and whether it increases or decreases will help to determine the impact of the drop in dose on prednisone induced activity. Prednisone increases water consumption and peeing and during reductions in dose I am specifically watching this behavior to see what the impact of lowering prednisone is in regard to their prednisone related behavior. Drinking, peeing, food drive and appetite, food aggression, general aggression, breathing and panting all tell me about whether I have seen the impact of a reduction or not. At very high doses one might not see much change, but as you get lower, there will be more obvious changes in prednisone induced side effects and in fact many will begin to cease and reverse.
So within 2 days and possibly even sooner, you might begin to see changes related to the reduced metabolism, or other changes that are related to the side effects of prednisone. These are important although not necessarily for the anemia, but rather the overall success of treatment. As a result of, or in parallel to, and depending on when the drop in dose is undertaken, anemia should remain either the same, or possibly improve. Since I do reductions early, I expect to see continued improvement relative to recovery from anemia. I might expect to see reduced intensity of the prednisone, but early on while still giving relatively high, immunosuppressive doses, I expect to continue to see high metabolic activity and plenty of side effects from the prednisone.
Prednisone Reductions and Watching for Anemia
Following any reduction I am watching for signs of increased anemia and desperately hoping to see none; that is anything that would indicate reversal or halting of recovery. Whatever behavior I have at the time of the drop in dose is usually the gauge from which you judge the effect of the drop. I do not want to see the head going lower, ears going down, pauses after excitement or instability return. I am certainly watching out or hesitation to eat, loss of appetite, but also for drops from their current activity level. Re-appearance of anemia may be quick, or slow even with the regenerative forms depending on the effect of prednisone at the current dose. It might slow the progression, or do nothing so the speed of reoccurrence of the anemia is not easy to predict.
What is certain is that the regenerative forms will relapse faster. RBC’s will be killed as soon as suppression fails and signs of anemia could begin almost immediately although more likely occur in parallel with the side effect changes of prednisone. Blood tests would show spherocytes and reduced RBC values as anemia increases. In Non-regenerative forms, the attack begins at a lower level leaving mature cells untouched, so monitoring blood for reticulocytes is essential throughout. If other cell types are impacted they need to be monitored too as one would expect drops in all cell types impacted by the relapse, or maybe not. Changes in RBC’s are really the only changes one can monitor closely and accurately with behavior.
Both conditions present their own challenges. Anemia can reappear quickly in the case of regenerative forms where the attack is on mature RBC’s. Although anemia is faster to appear, it is also faster to stop it by just returning to the previous dose. With Non-regenerative anemia, the attack may take longer to stop and RBC’s will need more time to be created once the attack is halted.
Other Issues with Prednisone Reductions
When withdrawing prednisone there are other signs to watch for as the body adjusts to the change in prednisone too that are not related to anemia like changes in stool consistency, infections, hair loss etc. that might need attention, but are not related to specifically AIHA and the return of anemia versus the continued suppression, or absence of the AIHA/IMHA attack.
There are also many other associated conditions that may be necessary to watch for along with anemia when removing prednisone or other immunosuppressive drugs. This article only goes as far as to detail the anemia, but the fact is that in many dogs, clotting, lack of clotting, platelet levels, WBC levels, thyroid output and many other related issues may be present or need to be watched out for in case they occur. The fact that I am not emphasizing them is to keep the focus on anemia, which is the only main problem associated with AIHA and potentially one of the primary problems being treated in cases of IMHA. Clotting and white blood cell changes may not be obvious in behavior, although infections and pain from them and other issues is often observed in behavior.
Aside from the fat that I am always checking my dog for infections and pain during the course of the disease, in fact as I reduce prednisone to a point where the adrenal glands kick in I need to specifically be aware that failure of the adrenal glands to start up and excrete cortisol after prednisone is reduced can result in lethargy and pain, discomfort similar to flu symptoms so again I need to be aware of additional behavior to keep an eye on in order to prevent this problem. This only occurs at doses of prednisone where the adrenal glands will need to work in order to keep the body at the correct level of metabolic activity and work for normal function and not at the initial high doses.
More to come!
More to come!