Canine Autoimmune Hemolytic Anemia (AIHA & IMHA) - Abnormal Clotting In Dogs with AIHA/IMHA

It saddens me that several of our members have recently lost their dogs possibly because of a blood clot. I just wanted some of you to know about the research that goes on under the radar and that there are many people who really care about finding a solution to this. Morris Animal Foundation provides funding for studies on many aspects of animal disease. You can view their website here: http://www.morrisanimalfoundation.org/ I have taken the liberty of searching and posting several of the studies that are directly related to abnormal and dangerous blood clotting in dogs with AIHA/IMHA. Joanne Dickson is our host here and has an accompanying website where she integrates information from Morris Animal Foundation into her extensive faq pages. You can see her pages here: http://www.cloudnet.com/~jdickson/index.html Below are three studies that the foundation has recently funded on blood clotting in dogs with AIHA/IMHA. my best patrice http://www.morrisanimalfoundation.org/our-research/results.html?animalspecies=dogs&study_area=blood-disorders&active=active&completed=completed&vssstudy= Examining Blood Clotting In Dogs With Immune-mediated Hemolytic Anemia Results: Student Work Indicates that Elevated Enzyme Levels May Increase Likelihood of Blood Clots Immune-mediated hemolytic anemia (IMHA) is the most common type of anemia in dogs. This deadly blood disorder occurs when something triggers a dog’s body to attack its own red blood cells. Despite aggressive immunosuppressive therapy, this disease has a very high mortality rate: most dogs die shortly after diagnosis. Many dogs with IMHA do not die of anemia, but instead, death is caused by blood clots that become lodged throughout the body and interfere with vital organ functions. No one has yet determined why dogs with IMHA are so prone to forming blood clots. The student aimed to understand the composition of hemoglobin, blood and plasma levels that cause these blood-clotting complications in dogs infected with IMHA. She hypothesized that hemoglobin and arginase release resulting from red blood cell destruction deplete nitric oxide and predispose dogs with IMHA to form blood clots. Results from this project showed that dogs with IMHA have elevated levels of arginase enzyme. Additional work will be necessary to determine how these elevated levels affect the role of nitric oxide in stopping bleeding. Changes in hemoglobin or nitric oxide were not detected, but there is reason to believe that this was because of the study parameters. The student hopes next to address the possible role of nitric oxide in IMHA. Future results could help prevent clots and improve survival. Principal Investigator: Erin McQuinn, Colorado State University Study ID: D09CA-601 Comparison of Aspirin and Heparin in Treating Dogs With IMHA Immune-mediated hemolytic anemia (IMHA), a common form of severe anemia in dogs, is associated with high mortality rates. Many dogs die due to related blood clots. Investigators will expand their previous research on heparin therapy, which showed that individually adjusted heparin dosing was significantly better than standard-dose heparin therapy in reducing mortality. A recent retrospective study reported improved survival in dogs with IMHA that received low-dose aspirin therapy, which resulted in aspirin becoming standard therapy for dogs with IMHA. However, multiple studies comparing aspirin to heparin in humans have shown marginal to no benefit with aspirin as opposed to significant reduction in blood clots with heparin. Researchers will establish whether aspirin or individually adjusted heparin therapy is more effective in enhancing survival in dogs with IMHA. Principal Investigator: Dr. David J. Polzin, University of Minnesota Co-sponsors: Meisha's Hope AIHA/IMHA Fund #338; Arlene & Ron Klein, in memory of Buttons; Evidence-based Veterinary Medicine Association (EBMA) Study ID: D10CA-026 Determing Causes of Abnormal Clotting Immune-mediated hemolytic anemia (IMHA) is a severe blood disorder that affects all breeds of dogs. Although dogs usually receive transfusion therapy to control their anemia, a frequent and often fatal complication of this disease is blood clot formation (thrombosis). Dogs with IMHA are often given anti-thrombotic drugs in the hopes of preventing these fatal blood clots. Determining what causes the clots would significantly improve veterinarians' ability to prevent them. This project aims to define the cause of abnormal clotting in dogs with IMHA, with the ultimate goal of developing an effective treatment strategy to improve patient survival. Principal Investigator: Dr. Tracy Stokol, Cornell University Co-sponsors: Meisha's Hope AIHA/IMHA Fund #338; Hill's Pet Nutrition, Inc., Mark L. Morris, Sr. Lifetime Achievement Award, honoring Dr. John Harvey; Heather and Paul Haaga; The Flat-Coated Retriever Foundation; Heather and Paul Haaga Study ID: D07CA-047

Patrice NYS

Patrice, Thank you for mentioning this. I have been meaning to so but the days keep getting away from me. Dr. Polzin's study at U of MN is a very important study that is going on now. We are in year two of this 3 year study and I get quarterly reports on this study which are very promising. The Meisha's Hope Fund just applied a huge chuunk of money to this study for the second year in a row: "Study ID: D09CA-601 Comparison of Aspirin and Heparin in Treating Dogs With IMHA Immune-mediated hemolytic anemia (IMHA), a common form of severe anemia in dogs, is associated with high mortality rates. Many dogs die due to related blood clots. Investigators will expand their previous research on heparin therapy, which showed that individually adjusted heparin dosing was significantly better than standard-dose heparin therapy in reducing mortality. A recent retrospective study reported improved survival in dogs with IMHA that received low-dose aspirin therapy, which resulted in aspirin becoming standard therapy for dogs with IMHA. However, multiple studies comparing aspirin to heparin in humans have shown marginal to no benefit with aspirin as opposed to significant reduction in blood clots with heparin. Researchers will establish whether aspirin or individually adjusted heparin therapy is more effective in enhancing survival in dogs with IMHA. Principal Investigator: Dr. David J. Polzin, University of Minnesota" We plan to to cosponsor the third year of this most important study as well but to do so we need lots of contibutions from people whose lives have been effected by AIHA/IMHA. You can contribute to the Meisha's Hope AIHA/IMHA Fund #338 at Morris Animal Foundation here: http://www.morrisanimalfoundation.org/meisha

Joanne MN

You can learn even more about the Meisha's Hope AIHA/IMHA Fund #338 at MAF at this page: http://www.cloudnet.com/~jdickson/newhope.htm

Joanne MN

I posted the wrong number of the study in my earlier post. The Study ID for Dr. Polzin is: Study ID: D10CA-026

Joanne MN

Patrice, I know I have to quite wondering what if about Dufy, but I think he probably did die from a blood clot. After I had read a little I started to give Dufy a baby aspirin a few days the last week he was alive but when I saw the Doctor the Saturday before he passed I asked her if it was O.K. to give him aspirin and she said I shouldn't do that because of his slight anemia. And he had a lot of trouble with his stomach for years so she advised me not to. Now I'm wondering if it would have made a difference. I just miss him so much. I wish everyone on here luck with there dogs for a quick recovery. Connie

Connie Washington

We are so torn up with our loss. We are going through all of the,"What If's" and wondering if we did everything that we could for Our Little Lucky? She was a Major part of our lives and now we feel such a big void. We heard from both the Specialist that was helping with Luckys Case and her vet. The Specialist said that Lucky had BLEW(?)a blood clot in her lungs. She had been on Aspirin since she was diagnosed with this Horrid Disease. We also got her blood Panel tests back from her Vet. They all came back Good. :( What did we do wrong? Where did we fail her? Sorry, We are having a bad time.....

Kathy Crestline

Patrice~ I have a question...Tori is now being treated for Evans Symdrone. I believe it is opposite of what you are talking about because the vet says she is not making enough platelets to clot the blood. What do I need to be aware of as we treat this with incresed Prednisone of 5mg every other day??? Her first blood test showed 48 platelets and yesterdays was 87. We had increased the pred from 5mg every 5 days to every 3 days. Now it is every other day. The vet wantsd the blood tested next week and see if we can get it to 127 or higher. She hasn't shown any sign of being sick, except the expected more frequent urinating at this time. Appetite is slightly up and slightly more water intake. Another question...her crit is holding at 40 - 43, so will I see weakness and panting and if so will this be because of the pred rather than lack of oxygen? This is such a confusing condition. Thank you for being there for us. Blessings, Cindi & Tori (IMHA/Evans Syndrome)

Cindi PCB

Cindi, This is somewhat tricky to explain but let me try. We are really talking here on this forum about 2 (or 3 or 4) different versions of canine blood disorders. If you look simply at the signs and symptoms of these conditions, you notice some big differences. Then once a vet has nailed a diagnosis, there are multiple causes for each particular disorder. Autoimmune is sort of a generic term and in fact has some variable terminologies that define more carefully the difference. AIHA Autoimmune hemolytic anemia is specifically a condition where the signs and symptoms are that red blood cells are being destroyed in circulation and the result is anemia, as defined by signs like the test CBC complete blood count, blood in urine and yellow mucous membranes etc. And symptoms like weakness, labored breathing or even collapse. AIHA is usually finally defined as an "intolerance of self." It is sometimes thought of as idiopathic, or without an identifiable cause. IMHA Immune Mediated Hemolytic Anemia. Okay, same signs and symptoms. So what is different here? Well, we are still talking about the immune system, but note that AUTO is missing from the word. We added a new word, MEDIATED. Medically this means that the condition is accomplished by means of an intervening medium or simply, there is an initial cause other than self. The immune system may still go awry but it is trying to fight against something it perceives as an outside invader. And often tests can identify an outside invader like a tick disease inside of the red blood cells etc. Treat the outside invader or cause and you may resolve the disease. Now, what my dog had and some very unlucky dogs have is a condition that does not involve destruction of red blood cells in circulation. So there is no hemolytic terminology. Hemo means blood and lytic means lyse and that is a medical term for a cell that destructs or ruptures. So what is happening if the cells are not self imploding in circulation? The process of making the red blood cells is somehow hampered in the bone marrow and this results in non-regenerative anemia. Maybe there is a form of cancer or there was ingestion of heavy metals or dangerous drugs. But, as Dr. Dodds encouraged me to understand, many dogs simply have an autoimmune destruction of the red blood cell precursor cells inside the bone marrow. Bone marrow failure. She has found that treating with very aggressive immunosuppressive drugs seems to resolve this very desperate situation. In addition, some dogs also stop making white blood cells. They are made from the same precursor cells in the bone marrow. This is an especially dangerous outcome because the dog loses the ability to fight off many kinds of opportunistic infections in the body. How can the immune system be so active in the bone marrow but be so ineffective in the rest of the body? It's puzzling, isn't it? Well, there are different elements of the immune system and some become more active (and destructive) by mistake. This condition is called neutropenia. Neutrophils are white blood cells and are in the largest numbers in our body. Penia means little or none. So it is an absence of neutrophils in the body. If you combine neutropenia and non-regenerative anemia (not making red blood cells) you can call this bicytopenia or the loss of two lines of cells that are made in the bone marrow. So Chance had bicytopenia. It's a very serious illness. A third, and even more dangerous, loss of cells made in the bone marrow is thrombocytopenia. Thrombocytes are platelets. They are also made from the same precursor cells in the bone marrow that the red and white blood cells come from. Why is this so dangerous? Inside our body, all day long and every day, our body has tiny little internal "wounds" that it needs to heal. Platelets with their cousins the clotting factors get together to fix these spots. They may be a small tear in the intestinal tract or a cut on the skin. If you don't have this constant healing process and rebuilding of tissues you can develop bleeding throughout your body. You have heard of people who are hemophiliacs. They do not have the proper clotting factors to help the platelets get together. If instead you have loss of platelets that means that the material that goes to help fix these wounds is missing. If you add all three of these losses of cell lines in the marrow together you have Evan's syndrome. There is a loss of red and white blood cells and platelets. This is an extremely aggressive condition. This is called pancytopenia or pan, which means all around or everything and cyto, cell, and penia, little or none. When you treat this condition you are really treating three different things. You have been successful treating Tori's red blood cell lines and now it looks like the platelets are beginning to respond as well. That is good. It means the aggressive treatments you gave have worked. Excellent! Now to answer your question about clotting or inappropriate clotting. Let's go back to the hemolytic anemia. Imagine, if you can, swimming around in a blood vessel. The body likes to package everything in there very carefully so when you look around you see all these types of cells floating in the plasma. You will see a lot of red blood cells that are concave, pliable cells that are full of hemoglobin. When oxygen attaches to the hemoglobin the cell will look red. What would the inside of that artery look like if those cells suddenly spilled all of that stuff into the plasma? All that stuff is floating around and needs to be removed ASAP. The body starts sending this to the kidneys and the liver saying "hey look at all this stuff, we've got to process this and get it out of here, it is blocking traffic!!! Hurry up!" The kidneys and liver become overloaded. They are used to handling a small amount of this stuff everyday when red blood cells get old and are destroyed by the spleen, but this situation is different. So you begin to see signs of this like yellow mucous membranes and red urine or feces. Researchers are still studying exactly why dogs with AIHA, who are in crisis like this, tend to begin to collect this stuff as clots in many places in the body. Inflammation of the vessels can contribute to this, as it does in humans, but dogs don't generally get atherosclerosis like humans do. So it may come down to a time element. The body is trying to get all this stuff out quickly, the kidneys and liver can't keep up and the body starts developing hot spots of inflammation and inappropriate clotting. It is clear that these dogs need some help recovering from this situation immediately. Research had shown that low dose aspirin has helped relieve this in the early days of hemolytic crisis. But now I have read new research that individually dosed/targeted heparin may be a better treatment for these dogs. It has been successful in human medicine. We may see this being used in the future for dogs. If the clots begin to form and they lose their attachment to the wall of the blood vessel, they can travel to the lungs and heart. This is very dangerous and can lead to sudden death. A dog that doesn't have enough platelets is at very serious risk for uncontrolled internal bleeding but there is no clotting happening. Yes, the side effects of the higher dose of prednisone is upsetting many body systems and that results in higher heart and breathing rate, increased appetite, drinking and peeing. There are many other side effects as well. If there isn't an increase in the platelets soon they will need to increase the pred dose. I know that Dr. Dodds has information on her website about using her blood products for platelet transfusions in these very serious emergency situations. They don't last long in circulation but they can buy some extra time. However, I do believe that thrombocytopenia is considered to be very responsive to high dose immunosuppressive treatment. You may see some positive upwards movement soon. You need keep Tori quiet. If there is a further decrease in platelets, you may need to have her in 24 hour care. my best patrice

Patrice NYS

Patrice, This post should be on the Meisha's Hope website! It is so understandable for lay people and informative to everybody intersected in the subject. Thank you so much for taking the time to explain. I will certainly keep this one! Cindy, Don't give up! Tori has come a long way and you have done an amazing job. o back to the success stories on the Meisha's Hope web site, there are a few dogs that suffered from Evans syndrome and recovered. best wishes, Brigitte

Brigitte BC

Brigette, Thank you! It's not explained exactly the way it should be and it's not so complete in my eyes. I missed mentioning a very important condition that can occur. DIC Disseminated Intravascular Coagulation (or consumptive coagulopathy or defibrination syndrome How do the platelets and the clotting factors work together to heal a wound? It is a complex process that involves many steps. And at each step of the way, there must be strict controls about how a wound is prepared and filled. The body will prepare a structure across the wound with fibrin, a strand like material, that provides a net-like foundation. The clotting factors activate the process of placing the platelets into the foundation. At some point in this process, there must be a signal that the job is done and stop forming the clot. Cells begin to migrate across this structure to lay down new tissue. There are *many* disease conditions where DIC can be a risk. AIHA/IMHA are just two of these conditions. So in a dog that has this condition, the normal vascular homeostasis is disrupted. This simply means that it's not business as usual. Red blood cells are being destroyed and as far as the circulatory system is concerned, this is a crisis. It wants to get back to normal and it has a variety of ways to attempt to accomplish that. Meanwhile the clotting processes continue, attempting to perform their regular function despite this crisis. At some tipping point, this process can become very disrupted. It can happen gradually or it can be very rapid. Clots begin to form abnormally. The mechanisms that tell it when and where to clot and when to stop become confused and there is systemic abnormal and inappropriate clotting. This uses up platelets at a rapid rate. Locations that needed clots are not attended to and sudden uncontrolled bleeding can begin. The body attempts to address this by sending out large quantities of fibrin into the circulatory system to halt the bleeding. Blood flow is disrupted as these thread like fibers crisscross the vessels and organs begin to fail. At this point, it is considered a medical crisis. An alert emergency veterinary team can begin a protocol to attempt to reverse this process. I know of several dog owners whose dogs were saved from DIC, but many more owners dogs do not survive this. The veterinary community may refer to DIC as "death is coming." You can imagine how complicated this is to explain to an owner. I barely understand all the physiology behind it myself, just enough to be able to attempt to explain it to you. So I think owners whose dogs succumb to this are left with an empty feeling. They don't understand what happened and they wonder if they did something wrong or not enough to save their dog. I stood and watched my vets while they did surgery on Chance to remove a large growth on his spleen. I knew the risks of DIC and I remember Dr. M saying quietly "hurry and get those vessels tied off, I am worried about DIC." I knew they were doing all they could but that it might happen suddenly and we might have lost him very quickly. Connie and Kathy are two of these owners. It is likely that Dufy and Lucky succumbed to this horrible condition and the vet just could not explain it in a way that Connie or Kathy would understand. I am so sorry. So the goal of research (not only in veterinary science but in human science as well) is to find out exactly what the process is that starts DIC and then to find the optimum protocol to halt it. Some research shows that heparin may help with this and they are at the point now where they understand that controlling the dosage of this drug carefully may be one factor that significantly helps the patient. my best patrice

Patrice NYS

Here is an article about DIC that was written by a vet for Veterinary Medicine in 1999. It is short but has a lot of medical terminology that you may not understand. Just scan it to get an idea of what the emergency protocol looks like. http://www.vspn.org/vspnsearch/aow/dic.htm my best patrice

Patrice NYS

Patrice~ Thank you for responding to my questions. I do believe I am understanding the condition better. If the WBC and RBC is slipping as I wrote on the Sept 15th post under Tori.... then we are in for another hard time in stablizing her... I'm thankful that she is happy, alert and is such a good little patient with taking her meds. Don't worry, Bridgette and Patrice I WILL NOT (by choice) see this as hopeless. We are grateful for every good day. Can't help wondering though...Is there any pain associated with this Eveans Syndrome? Our vet said that Tori wasn't in pain with the IMHA. We just don't want her to hurt. Thank you, Cindi & Tori (IMHA/Evans Syndrome)

Cindi PCB

No, I doubt there is pain, other than what is caused by the side effects of taking long term, high dose prednisone. With bone marrow failure there is a slow decline of numbers. I remember Chance seemed so normal for so long after he was diagnosed. But his numbers dropped slowly and steadily. Once he reached a PCV of 18, it was different. He did not feel good, but I doubt he was in pain. Never-the-less he was not himself. Dogs will be very different from their normal behavior when they are truly in pain. You may have never seen them behave this way. Evaluate how they feel by how eager they are to continue to be part of the household daily activities. Even when Chance was very sick, he would manage to get down the deck stairs to bark at a squirrel. I had to honor his continued will to live. Have faith in your dog to let you know. my best patrice

Patrice NYS

Hi, For some reason I am blocked on my usual IP address, but I have more than one connection, so I will try posting my question again. Thanks for the references/studies and the excellent and informative explanations once again. I have always been a big believer in individual dosing, although I know it does not matter as much with some drugs as their effects occur over a broad range and individual differences seem to matter less. This was my experience with pharmacology in our lab back in the 90's. Do you think individual dosing is important with prednisone, or the immunosuppressants? I ask, because Dylan seemed much more reactive than any dog I have seen since I found myself frequenting this list and other AIHA/IMHA resources. She was unable to lift her head after 4 weeks and many dogs are on that same hi dose for 8 and 10 weeks and do not see near the impact as on Dylan did after 4. If Dylan does experience a relapse, I don't plan to start her at the same 100 mg/day (2 mg/lb/day split into 2 doses) and plan to reduce that to 1 mg and go from there. I am very interested in any opinions on this, since I would like to be as prepared as possible for a relapse. Dylan is doing great and I am working on building her health and physical strength back so she could withstand another fight. I also want to do what I can to prevent her from suffering unnecessarily from the effects of too much prednisone. I understand the next attack may not be the same acute attack and that her circumstances might be significantly different from the last one, but her reactivity to prednisone was so intense and worked quickly. If you a have a moment, I sure would appreciate our opinion and anyone else' for that matter. Richard and Dog Dylan

Richard Burnaby

Richard, I totally get it that you want to be prepared for a possible relapse, but don't get to obsessed with it. try to relax.... I know that is easier said than done. I would imagine that Dylan would respond to 1mg per lbs. But that would ultimately be your and your vets decision. For Kahlu we treated at 1.5 mg pred per pound and 50 mg azathioprene. at the relapse we did the same pred dose but added co Los Orin instead of aza. but as you know it was not meant to be........ (DIC) Thanks for that link Patrice!All lthough it still hurts, it is so good to get the information. It is all relative. Here I am sitting in a hotel with my 2 healthy poodles. they had a great first day at the agility trial with lots of good qualifying runs. life will never be the same after this disease, I appreciate my healthy boys so much and can't understand how some people can be mad at their dogs for not performing perfectly. Their lives are to short for stuff like that....... best wishes, Brigitte and the super star poodle boys

Brigitte BC

Hi Brigitte, Glad to hear you are always having fun with your dogs. Don't worry about me, I am not obsessing. I have been prepared for a relapse for some time, since they occur and I intend to save Dylan again if I have to, that is all. I have not stopped trying to know more about this so I am better prepared is all. I learn, it is what I do full time whether it is dogs, AIHA, or IT work. And I am certain my vets and I will make the decision together. All decisions in the past were made together and in fact have been left to me on many occasions to make the final decision based on our discussion of options. Even my vets know that there are no solid facts in this disease and I am fairly certain they would agree to start at a lower dose next time anyways due to the excessive reaction last time. I will ask them too when I get a chance. My vets give me a lot of the credit for getting her through it the last time and I really appreciate the fact that we work together to make decisions and not alone. Even with Jagger before that, they respect me and therefore I am heavily involved in discussions and decisions. Since I am fairly well educated and I know my dogs extremely well, even if it were something else, it has always been the same in that it is a team effort to solve problems. I know how I feel about prednisone and I know Patrice has always tried to get people to reduce prednisone in a timely manner if possible (from my observations here) and is very knowledgeable about this, so I value her opinion as well as anyone else' here. I know less about the immunosuppressants and that is really what I am more interested in as far as individual dosing. Again, Patrice and others here have a lot more knowledge than me. It is related to this topic although not 100% so I could start a new thread, or see what happens here first. Richard and Dylan (10 year old rejuvenated puppy)

Richard Burnaby

Patrice, Thank you for your explanation. It is very helpful and I am hoping that I can start to remember Dufy when he was healthy and happy. I still miss him so so much and can't get those last moments out of my mind when he was looking at me and trying to breath. I just hope he was not in to much pain. I cry myself to sleep almost every night. I know that he had a good life and I did everything I could for him. I just miss him. Thank you, Connie

Connie Washington

This thread was discussed between 07/09/2011 and 18/09/2011

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