IMHA - Looking for Answers

The Basenji, West Highland White terrier, English Springer Spaniel, Alaskan Malamute, Poodle and Beagle breeds can be congenitally predisposed to thiscondition due to defectsin enzymes (such as pyruvate kinase) or in the red blood cells.

Heartgard (Rx) and Interceptor (Rx) both come under a lot of scrutinyas potential causesof immune mediated hemolytic anemia (IMHA) and immune mediated thrombocytopenia(ITP)because they are often the only medications that a pet is on whenthese occur. There is noevidence at this time of an increase in the cases of IMHA or ITPin dogs on these preventatives.

IMHA after Vaccination and "Transfer Factors"

Q: I am a new subscriber to your service. My 11 1/2 year old Brittany came down with IMHA ten days after her DHLPC+ Parvo vaccination. It has been going on for 14 days now. In bebeginning her PCV levels were 20,9 and went down to 10. She was givenOxyglobin 3 times, and she is on 60mg of Prednisone, 1.8ml of Cyclosporum, 25 mg of Carafate twice a day. She was also on Azathioprine 25 mg, but we have now taken her off that. Her PCV has raisen to 22 and been steady, but we do not seem to get any higher. I was told to try Transfer Factors on her. Do you know anything about them?Anything else we could do?I really would appreciate some info ASAP.Many thanks, Tia

A: Tia-

The February 15, 2001 issue of the AVMA Journal, which I received today,has an article reviewing the use of medications for immune mediatedhemolytic anemia (IMHA). The authors are Sophie Grundy and ClaudiaBarton.

I read this and the medications that are mentioned are prednisone, dexamethasone, azathioprine (Imuran Rx), danazol, cyclosporine (Sandimune Rx), cyclophosphamide, bovine hemoglobin (Oxyglobin Rx) and humanimmunoglobulin (currently unavailable, I think).

Of these medications, only cyclophosphamide and bovine hemoglobin appeared to cause an increase in mortality. I was very surprised by the inclusion of Oxyglobin in this short list, because I would have guessed it would be beneficial.

To the best of my ability to interpret the results of this study, there did not appear to be any major impact on survival using multiple medicationsover using prednisone alone.

Among veterinarians who commonly treat IMHA, I am pretty sure that the preference of most vets would be 1) dexamethasone or prednisone inthe very early treatment, almost always switching to prednisone alone quickly 2)azathioprine as the most commonly used secondary medication. There wasn't astatistical benefit in using this medication in survival times but it mayhelp to reduce side effects from steroids 3) cyclosporin is the newest medication being used for IMHA and some vets like it a lot. It works betterand is safer if the dosage is adjusted based on serum levels, with 500ng/ml being the lowest dosage thought to be effective and 1000ng/ml about the level at which immunosuppression becomes severe enough to be a problem. Ithink a lot of vets would use the human immunoglobulin if it were availableand/or less expensive.

I could not find any information on "transfer factors", so I am not sure what this references. It is possible that this could be a reference tousing fresh frozen plasma or cryoprecipitate to get blood clotting factors but that is usually an emergency recommendation for use when the hemocrit(PCV) is very low or when platelets are also low or not functioning properly.

It is extremely important to continue to look for an underlying cause for IMHA, especially in older patients, since it can be associated with certain forms of cancer (hemangiosarcoma and other malignant cancers) and can occur due to drug and toxin exposure. It is more common in the month aftervaccination, too.

I usually stick to prednisone and I wouldn't be too upset by the progress you have seen so far -- but I would still want to keep looking for an underlying problem. Some dogs take longer to recover than others. We have had to treat with prednisone for several months on a daily basis in some dogs. We do use azathioprine occasionally, especially if dogs seem to behaving trouble with daily prednisone.

I wish that I did have a really good suggestion for a medication that would be reliably better than the others.

Mike Richards, DVM 2/15/2001

Known Causes of Immune Mediated Hemolytic Anemia (IMHA)

Q: Dear Dr. Richards, I am a subscriber to your service. I havea question about immunemediated hemolytic anemia, IMHA. On November 8, 2000, my six year old femaleschnauzer, Indy Anna, died from IMHA. Three days prior, she was healthy and we walked our normal 2 1/2miles. She was my closest buddy, and I am grieved by her loss. I read quite a bit of exchange on this server about this disease. I realize that there is not a clear cause and effect relationship in regard to it. Yet, I would like to know all the possible causes of this horrible disease. I have talked to my local vet and to the vets at Purdue University,who tried valiantly to save my dog.

My question is: what caused Indy to get IMHA? Is there some predilection to this disease in Schnauzers? Is there something I did that brought on this disease? Could I have saved her?Did my local vet act wisely?

Here is some information to assist your answer. Over the summer, Indy showed a high level of Alkaline Phosphate in her complete blood test. We dida low-dose DEX test, an ACTH test, a liver x-ray, and a liver sonagram to determine cause, possibly Cushings Disease. Nothing was found. Results were sent to Purdue University for consultation. Advice: liver is a bit discolored, retest in 4 months (December). Indy had pancreatitis for two years. It was under control with Canine ID food. According to blood tests at the time of her illness, she was not suffering from either Pancreatitis or Cushings. Indy took Sentinel monthly. We used Frontline Advantage for 3 months over the summer. She took a glyco-nutrient daily. She had not had Sentinelfor a month prior to onset of IMHA. She had not had vaccinations for almost a year. She was slightly overweight, 19 pounds. We fought weight her entire life. She was very athletic, having walked long distances daily. Indy became ill during the night on Sunday, Nov.5th. She vomited twice. On Monday morning, she collapsed, breathing hard. I took her to the vet immediately. On the table, Indy's head hung way down. The vet gave her IV fluids (under her skin), an antibiotic shot, and took blood (the blood work was not done STAT). She sent her home. By 6:00 pm, Indy was weaker. I took her back to the vet. She was hospitalized locally overnight.The vet thought she was in shock and started treatment, I think with steroids. At 7:00 am. I received a call that she was doing well. At 8:00 am,the blood tests were back and showed IMHA. The vet did steroid treatment . I arrived at 8:30 to check on Indy. I was told we might lose her. Imagine my shock and dismay! My husband rushed to Bloomington, IN from Indianapolis(where he works) and we took Indy to Purdue's small animal hospital, emergency care. Her hemoglobin was at 8. Indy rejected three transfusions. We then gave her oxyglobin and plasma. She had massive steroids. She stablized a bit. I went home to get a car and pack a bag for an extended stay. Then, in the very early morning,she went down, probably from a blood clot to her lungs. The vets knew I was on the highway and 1 1/2 hours away from the clinic, and they worked to save her. They put her on a respirator and massaged her heart externally.They brought her back five times. I arrived and was able to talk to Indy,whenher heart stopped a sixth time, I let her go. Thank you for your response to this note. You can publish it if you like. Sincerely, Lynne

A: Lynne-

These are the known causes of immune mediated hemolytic anemia (IMHA) that I know of:

• Genetic predisposition to this condition is known to occur in the following breeds:American cocker spaniels (most common breed to develop IMHA), English Springer Spaniel, Old English sheepdog, Irish Setter, Poodle, Dachshund(list from "Textbook of Internal Medicine, 5th Ed., Ettinger and Feldman)
• Drugs that might induce IMHA:sulfonamidescephalosporinspenicillinsmethimazoleprocainamide
• A higher incidence of IMHA is seen in dogs within a month of vaccinations so it is presumed at the present time that some dogs react to vaccination by developing IMHA.
• Metastatic cancer, especially hemangiosarcoma, is a common cause of IMHA in older dogs.
• Tick borne illnesses, usually ehrlichiosis but possibly Rocky Mountain spotted fever and Lyme disease can lead to IMHA.
• Severe bacterial infections (sepsis, for example) and some viral illnesses(more common in cats) can lead to IMHA.

Most cases of immune mediated hemolytic anemia are still unexplained (idiopathic) at this time. Hopefully, it will be possible to identify more and more causes of this condition as time goes on and perhaps some day to beable to definitively identify a cause in individual patients for which an obvious cause, such as metastatic cancer, is not present.

We have seen two cases of IMHA in schnauzers secondary to hemangiosarcoma.In both of these cases, the IMHA was recognized prior to recognition of the cancer, despite the fact that one of the dogs was examined by a good practice in the owner's home town, a good emergency veterinary clinic and by our practice. In fact, in that particular patient, we had to do a post-mortem examination to find the cancer. I am not sure if this is a common occurrence in other practices, but it doesn't seem to be reported in the literature, if it is.

I can't imagine what more you could have done to save Indy Anna. You did all the right things, seeking veterinary care early, making the decision to go to a veterinary school, using oxyglobin when transfusion was not helping and the care as things went along seems very appropriate. I often wish that making the right decisions would guarantee the right outcome, but that just isn't something that happens all the time in veterinary medicine. You did well for Indy Anna and you should not worry that you did not do enough.It is extraordinarily hard to lose a friend when there is no clear explanation of what happened.

Mike Richards, DVM 11/26/2000

Other Medications for IMHA

Q: Dear Doctor Mike, My 7 year-old yellow lab is very sick and my family has pretty much accepted the fact that she is going to die very soon. I on the other hand, am having a very difficult time with this and need to make sure we have explored all of our options. We have taken bone marrow samples and determined she does not have cancer. They think she has Autoimmune Hemolytic Anemia and her red blood cell count has dropped to a fraction of normal levels. We have tried chemotherapy but she started having severe side effects so we decided to stop treatment.She is currently taking cortisone shots which seem to help her appetite but she is not getting any better. I have read that cyclophosphamide and prednisone have been effective in other cases and I wanted to know if you had any other suggestions. I'm very concerned that she could die at anytime so if you could respond quickly it would mean a lot to me. Thanksin advance for your help. Sincerely, Geoffrey

A: Geoffrey-

Immune mediated hemolytic anemia (IMHA) can be very difficult to treat successfully. It is hard to distinguish from problems caused by hemangiosarcoma (a form of cancer) in dogs and our experience has been that Labs are more prone to this than most breeds. While seven years of age would be young for this cancer to occur we have seen it in Labradors and golden retrievers in this age range.

When standard therapy using corticosteroids and other immunosuppressive agents doesn't work it may be worthwhile to consider trying Danazole (Rx).This medication has been reported to be beneficial in some cases of IMHA.The June issue of the AVMA journal had an article on using human immunoglobulins for this but it was only helpful in some dogs. I have no idea how one acquires this product, though. I have not seen references to using cyclophosphamide for IMHA but have seen references to using this for immune mediated thrombocytopenia(loss of platelets). These are markedly different disease processes. We see ITP most commonly as a drug reaction and withdrawal of the offending drug, along with corticosteroids, works very well to stop the clinical signs in most dogs.

I hope that improvement did occur since you wrote.

Mike Richards, DVM

IMHA Caused by Heartworm Medicine?

Q: Dr. Mike, I have a 10 year old Cocker Spaniel who has just fallen ill with Autoimmune Hemolytic Anemia. I found my dog wavering and eventually collapsing.I took him to my vet who checked his PCV. It registered 21 and eventually fell to 13. At that point the vet gave him a blood transfusion along with steroids and Cytoxin. He has responded quite well. Hiscurrent PCV is 34 (two days after the transfusion. I am concerned however because the doctor can find no underlying cause for this disease in my dog. Also,because my dog responded so quickly, I almost feel that the doctors are uncertain now that this is actually AIHA. My only suspicion if it is indeed AIHA is that I gave my doga 30 day chewable Heartguard two days prior to his collapse. Could this be a factor?Also, I am quite concerned about his future. If a dog is diagnosed with this disease, but no cause for the disease is found,what is his chance of recovery without coming down with the disease again? I'm worried,because he stays home by himself all day while I work and I can't monitor his condition.Do you have any advice? Thanks! Brian

A: Brian- I am almost afraid to answer your questionas I have been in a long email discussion over this issue recently. I believe that in any individual dog, almost any medication can have almost any side effect. Therefore, I have to say that I think Heartgard(Rx) could potentially cause immune mediated hemolytic anemia (IMHA). BUT -- I think it is not very likely. I get this exact question relating to all of the medications used on a consistent basis -- Heartgard(Rx), Interceptor (Rx), Frontline (Rx), Advantage (Rx), Program (Rx)and probably others I can't remember offhand. All of these are recently developed medicationsand we saw IMHA in our practice many times prior to their development.

To judge if these medications are having an effect, in general, it is necessary to compare the expected rate of IMHA in the population to the rate of IMHA in the population when one of these products is being used. All of the companies currently claim that the rate of IMHA is no greater when their products are used than when they are not. I hav eno way of being sure of this but these are reputable pharmaceutical companies and I have no reason to doubt their word at the present time.

To judge if one of these products is causing IMHA in an individual maybe impossible and is atleast very difficult if the product is not used again. Many clients opt not to try further use of a product they think might have caused IMHA since there are alternative medications for each of the products most frequently suspected. In some instances death of the pet precludes this sort of decision and leaves pet owners very confused and sometimes angry.This is especially frustrating since there is no way I know of to prove or disprove the theory that the IMHA was induced bya product after the death of the pet. If you want to, you can administer Heartgard in the futureand if there is no recurrence of the IHMA it would be less likely tohave induced this problem.I think I would be comfortable doing that in the case of Heartgard but if you are not, justc hange medications for heartworm prevention since others are available.

IMHA can recur but often it does not. I hope it will not for your dog.

I hope this helps and does not just muddy the water more for you.

Mike Richards, DVM

IMHA in Poodles

Q: Dr. Mike, Today i learned that my poodle, pierre,who is six may have this disorder. he is epileptic and has taken phenobarb since he was 4 months old,could this have brought it on. my vet will consult with me again in a few hours but thought i would get another opinion on this. my family is devastated! three days ago pierre was fine. whatt o do now? what are his chances? any comments would be greatly appreciated.D'Ann

A : D'Ann-

Several medications can lead to problems with immune mediated hemolyticanemia (IMHA)and phenobarbital is one of them. This is not a very common effect,though. Poodles are predisposed to IMHA and it is harder in them to sort through possible causes, since the condition occurs for no apparent reason in poodles more frequently than in most dog breeds.The success rate in treating this condition varies widely. It is usually not a good idea to abruptly stop giving phenobarbital, especially in an epileptic patient.This can make therapya little more difficult if it is part of the problem but usually drug induced IMHA is easier to treat than "naturally occurring" IMHA, so that helps. I am hoping Pierre is doing much better now.

Mike Richards, DVM

IMHA, Heartgard And Liver Shunts

Q: My toy poodle Buttons was fine until recentlywhen we started her on herheartworm medication, the one month chewable variety. The next day she became very lethargic and weak almost to the point of not being able to stand.I rushed he rto the vet early this morning and they diagnosed her with a very lowred blood cell count something like 14 instead of the normal 35. Her temperature was normal at102, according to the vet. She was put on a large dose of steroids at 10:30 AMand this evening the vet called and said she had gained her red bloodcell count very slightly. He seems to think she may be out of danger, but I'm still very concerned.I also came across something on the web referring to "shunts" in pets, namely small dogs such as toy poodles. The vet has no idea what may have caused it. The medication is Heartgard Plus by Merck which contains ivermectin/pyrantel.Could you please give me your opinion on this and any further recommended treatment?Also, does this sound curable? Thanks, Tom

A: Tom- Liver shunts are a congenital problem insome dogs. During gestation the placenta delivers blood with food and oxygen from the mother through the umbilical vein. This means that in the fetus, circulation is the reverse of circulation after birth, because the fetus' veins have the oxygenated blood and arteries return unoxygentated blood to the heart. In order to makethis work, there is a shunt from the liver venous circulation to the arterial circulation. At birth,the pressure within the circulatory system changes as respiration occursand this shuts the shunt,which eventually disappears. If this reverse in circulation doesn't happen for some reason, the liver is deprived of a blood supply and doesn't develop properly after birth. Many puppies can live with the small functioning portion of the liver for some time but eventually have problems and usually die if the situation is uncorrected. It is possible to surgically close the shunt and the surgery works well. I can remember hearing of one sheltie that was 6 yearsof age (or possibly older)before a congenital liver shunt was recognized, so some dogs can live a long time with this problem.It is very unlikely that your poodle is experiencing problems from a liver shunt.

Note: Heartgard (Rx) and Interceptor (Rx) both come under a lot of scrutinyas potential causes of immune medicated hemolytic anemia (IMHA) and immune mediatedthrombocytopenia (ITP) because they are often the only medicationsthat a pet is on when these occur. There is no evidence at this time of an increase in the cases of IMHA or ITP in dogs on these preventatives.

Recently,the once monthly flea treatments have also been subjected to some suspicion since theyare the newest medications many dogs are on when these problems occur. There is also no evidence that they cause either of these conditions, presently. That doesn't mean new information won'tcome to light at some future time but I honestly do not suspect these medications as culprits in these diseases.

Mike Richards, DVM

Heartgard, Immune Mediated Hemolytic Anemia and Petitions Q: Dr. Mike, I am writing you to let you know that all evidence now points to Heartgard with Ivermectin as being the drug that triggered Immune mediated hemolyticanemia in my toy poodle, which eventually died. Ivermectin is a potential killer,period. I would appreciate you and others like you getting the word out that the big drug manufacturers are poisoning our pets with chemicals like these. If I have to call and email every vet in the US, I will. I will also go to every chat room and site where people go to get info about pets on the internet, to let them know the dangers of Ivermectin,because I know that Merck and the others will simply sweep it under the rug. Tom

A: Tom- If you were able to convince pet owners not to use ivermectin you would be doing a grave disservice to a great number of pet owners. Heartworms kill many more dogs than immune mediated hemolytic anemia ever will, even if ivermectin does trigger this response in some dogs. There are analogous situations in many areas of life. Once in a while, wearing a seatbelt will kill a motorist in an accident instead of saving their life.Overall, though, seatbelts save lives. The family of a person who dies because of the seatbelt feels cheated and wishes that their loved one was not wearing it. Their sentiments are real and they can legitimately say that the seatbelt killed their relative. But it would still be wrong to campaign against seatbelts.

I know you hurt. I wish that I could encourage you in your actions.Please let me know what information (evidence) you have that leads you to be so sure that ivermectinwas the underlying cause of the IMHA. I really do not know of a way to confirm this suspicion-- or to disprove it.

Mike Richards, DVM

IMHA and Heartgard -Not Necessarily Cause and Effect

Q: Dr Mike, Thanks for posting my original questionon your site. Here is what happened over the past several days with my toy poodle which has been in perfect health for all her life, except for an occasional pinched nerve in her back that acts up. I had her blood tested for heartworms and got the ok to start her on heartgard which I did a little over a week ago. Two days later she started to lose her appetite. By the third day she was very lethargic and beginning to sway as if about to falldown. I rushed her to the vet and noticed her gums were almost gray. Thevet immediately put her on steroids to stabilize her. Her red blood cellcount was down to 14 from a normal 35 or so. She has been under 24 ICUfor the last 3 days and is finally coming around after several transfusions,intravenous medications and whatever else you can think of. She was tested for everything under the sun and was found to have immune mediated hemalyticanemia which you mentioned in your first reply to me. All of the doctors involved asked is she had received any medication at all recently in the way of shots or whatever, which she hadn't...except for the Heartgard Plus30 day chewable. My suspicions lie with this medication, but just about every one of the drs. are unwilling to point the finger at it. I found the test results of the drug when Merck first came out with it and someof the possible adverse side effects fit the pattern of what was happening to my dog. It almost seems as if nobody dares to pin possible dangerous side effects on this drug. I definitely am and intend to pursue it as far as possible, maybe even seeing if Merck will pay my nearly $2000 vet bills.I visited the dog tonight and it looks as though she's on the road backand with any luck I'll have her home in the next few days. Just wantedto give you an update because you're the only doctor out of the many I'veconferred with in the last week (I even called Merck) who dares to place a possible connection here. Would like your further input on this if possibleand what you think I could do further. Thanks again, Tom

A: Tom- It is always difficult for clients to understand immune mediated hemolytic anemia (IMHA) and immune mediated thrombocytopenia (ITP). People seem to naturally look for "cause and effect" relationships whenever problems occur. While there often is an underlying cause for theseand other problems there often is not. The medications that are used ona frequent or fairly frequent basis often get blamed for lots of problems that are not due to them because of this need to find a cause for every effect. This is especially confusing in the case of IMHA and ITP because there are definite known inciting medications and therefore there is astrong tendency to look for a inciting cause among medications the pet is on.

The monthly heartworm preventatives have been very beneficial for our patients. They have drastically reduced the number of dogs we treat for heartworms each year. I can understand the reluctance of veterinarians to consider them as a possible cause of conditions such as this. Despite this, it is necessary to be realistic and accept that any medication can cause problems in a few individuals. Since these are extremely beneficial medications, that risk would be acceptable even if it were known to exist.

As I think I pointed out in the first letter, I am not aware of a relationship between ivermectin (Heartgard Rx) and immune mediated hemolytic anemia.Despite that, I think it has to be considered as a possible cause. I thinkit is important to notify Merck that this happened so that it is documented- in case the number of reported cases does start to exceed the number expected in the general population of dogs on Heartgard. The currentlyavailable information suggests that the expected number of cases of IMHA in the population of dogs taking monthly heartworm preventatives has not been exceeded -- making it unlikely that there is a cause and effect relationship between the IMHA and the ivermectin.

If you live in a heartworm endemic area, you need to use a heartworm preventative. Switching to milbemycin (Interceptor Rx) may relieve thew orry of continued use of ivermectin (Heartgard Rx). It was good to reportthis to Merck. If there is a problem, eventually it will surface if people continue to do this. Until it is proven, though, I can see no reason toget angry with Merck. Continue to work with your vet to ensure that yourdog keeps on improving. I know it is hard to accept that some things jus thappen -- but it seems to be the case.

Mike Richards, DVM

IMHA and Ivermectin - continued - more cases Reply from previous email: Dear Dr. Richards, In response to your email regarding my toy poodle, ivermectin, and IMHA, I just want to say, that,you are right...I hurt, more than you can imagine. That little bundle of joy was such an important part of my life for 9 years, it would take me 9 years just to describe how much. The pain of losing her in such a way is truly horrible. It has been 4 weeks now and I still wake in the middle of the night thinking of what she went through. I have come across a number of breeders who will not even administer ivermectin to their dogs. In calling around to local vets, I have also have even found some who will not recommend it for certain breeds, because of their seeming susceptibility to adverse reactions. Cockers, collies, and poodles being among them. To answer youa bout doing an injustice to other dog owners, it sure sounds to me like you've done a bit of a 180 here from your first responses to my concerns about ivermectin, where you "believed" there could be a connection. Nowyou seem to be saying that there are SO many dogs on this drug, that a few adverse reactions should somehow be accepted! Boy, it sure sounds like the response I've been getting when I talk to the people at Merck. For the good of the cause...well, tell that to my precious little girl who,in my mind, should still be here with me as I write this. I know that drugs like Heartgard/ivermectin are HUGE money makers for Merck AND a the vets who carry the line. I certainly hope that it wouldn't cloud this whole issue of investigating this whole thing. And, besides, aren't there alternative heartworm medications such as Interceptor (recommended over Heartgard by many of the breeders I spoke to, by the way) and the daily dosage medications?I just don't understand your concern here. MY main contention is this: Apparently there are a number of breeds of dogs that are susceptible to things like IMHA, whether because of genetic predisposition's or whatever. Merck knows this as well as the veterinary community. I want to know whythis is not in the information that comes with the drug? If I had even known there was a possibility of an adverse reaction in my dog, do youthink I would have given it to her? I blame Merck for this first and my vet second. I have come across several people who have posted to a site on the internet referring to IMHA. Keep in mind, these are just a few who have access to the internet. I'd be willing to bet there are MANY moreout there experiencing the same thing, but have no way to make it known,or don't even think to make the connection between ivermectin and IMHA.

Yet another Cocker Spaniel... "I have a 10 year old Cocker Spaniel named Casey. He is in amazingly good health for a 10 year old dog. However on June 19th, I noticed that he was swaying back and forth and ultimately collapsed. He did a similar thing on the 19th and I took him to the vet on the 20th. He was immediately diagnosed with AIHA and admitted to an Emergency Veterinary Hospital. His PCV was at 21 when admitted and dropped to 13. He was given a transfusion, cytoxin, and steroids and now three days later his PCV is up to 34 and stable. I can only hope that his healthcontinues to improve. I feel pretty helpless. The doctors are unable todeduce what could have caused the onset of this, because there are no otherexisting factors that normally are seen with this disease (cancer, hemorrhaging,etc) but from reading your comments I am suspicious of a possible factor.The ONLY medication given to Casey was Heartgard 30 Day Chewables on June17th. I have to think there is some correlation, especially since so manyothers have had the same experience. My thoughts and prayers are with therest of you going through this horrible ordeal." Brian

"My sympathies to all of you who lost your dogs. I nearly lost mine,and am still dealing with her recovery. First, I think the possible connectionof heartworm medication and AIHA is worth looking into. But don't lookto mainstream vets for much support. Merck has a clever legal staff whosemain line of defense would probably be that the autoimmune disorder exacerbatedthe effects of the medication. Look into it anyway."

"I'm just stunned. My dog, a precious springer spaniel, 4 1/2 year oldfemale, was diagnosed with IMHA 2 days ago. She is hospitalized and beingtreated in a similar manner as I've read here. The thought of losing heris devastating, but as a nurse, I understand. The amazing thing is thatHeartguard also crossed my mind as the vets were quizzing me about her,habits, drugs. She has taken it in 3 previous years without problem, shehas had 2 doses of the 6 for this year. I will share these notes with myvet, also please keep me informed about more info discovered and othercases. In the other cases involving Heartguard, had the dog had the drugin previous years, did the hemolytic anemia develop after the first dose.As I'm hoping and praying for my dog's recovery, I wish others the bestand my condolences to those of you who have lost your friends." Kathy

"Two years ago, my perfectly healthy black lab got violently ill 2 daysafter giving it Heartgard. It was the only medication I had given the dogin the previous weeks. It had severe vomiting and diarrahea. After a fewdays, it couldn't even walk...it died within a week. My suspicions wentimmediately to the Heartgard, but upon asking my husband his opinion, hebasically said there was no way, so I forgot about the whole thing andnever thought anything else about it." (Isn't one of the most common adversereactions to ivermectin is vomiting and diarrhea?) Grace

Tom, So very sorry that you lost your precious toy poodle, and I amsorry to be so slow in replying...I have been out of town for 2 1/2 weeksand had no access to internet. Ivermectin IS controversial. There is somesuggestion, as noted by Dr. Jean Dodds in a seminar recently, that thelarge molecules in ivermectin and some of the other drugs given to dogsmay initiate an autoimmune disease in those animals predisposed by hormonalstates, heredity, or other environmental exposures. It has not yet beenwell established that ivermectin can cause hemolytic anemia, but it maypossibly be a contributing factor. I hope that you are able to find anotherpuppy ASAP to fill the large cavity left in your life by the departureof your little toy poodle. My sincere sympathy! Grace

In closing, Dr. Richards, I will not and can not let this drop. I KNOWin my heart that ivermectin triggered IMHA in my little girl. I KNOW sheshould still be here. I KNOW that Merck doesn't really care, and is willingto write off a few unfortunates like my Buttons, for the sake of the largeprofits. I also BELIEVE there is a lot more of this going on out there,that simply has not surfaced yet, but that in time, it will. Lastly, isn'tit interesting that Merck is now using a photo of a Collie in it's promotionalcampaign for Heartgard. Of course we know that this is the dog MOST adverselyaffected by Ivermectin. What's THAT tell you about Merck? Very distraughtand frustrated, Tom

A: Tom- I do think that there is a possible connectionbetween the use of ivermectin and IMHA in your dog's case. As you continueto research this I think you will find the same connections made to mostmedications that are used on a routine basis, including milbemycin (Interceptor),vaccinations, seizure control medications, monthly flea control productsand antibiotics. This is where the difficulty comes when discussing IMHA-- is the incidence of reactions in dogs on ivermectin higher than thethe incidence of IMHA in the general population? I can not answer thisquestion with much authority because these sorts of figures are very hardto come by in veterinary medicine in general -- we simply have no goodcentral tracking method such as insurance companies or a "Center for VeterinaryDisease Control" I think it is wrong to assume that ivermectin could notbe the cause of the problem, though. I know this is confusing and not entirelysatisfactory to you.

I know of no studies suggesting an increase in sensitivity to ivermectinin poodles or cocker spaniels. There is evidence that collies are moresusceptible to ivermectin toxicity but the dose range necessary for toxicityis at least 16 times higher than the dosage necessary to control heartwormsand because of this Heartgard (Rx), containing ivermectin, is approvedfor use in all dog breeds for the control of heartworms.

Since ivermectin is only present in the body in significant amountsfor about 3 days after administration of a Heartgard tablet I was hopingthat your dog would recover from the IMHA, as withdrawal of the offendingmedication in combination with therapy is often sufficient to stop thehemolytic anemia. Had this been the case I would have advocated using analternative heartworm preventative in the future, in your dog's individualcase. But I would not and can not advocate discontinuing the use of thismedication in the majority of dogs as it has been extremely beneficialfor a great number of dogs.

It took me several years to get over the loss of my high school andcollege buddy, a labrador retriever, who died during an anesthetic procedure.For a very long time I suspected carelessness or fault on the part of thevet who was working on her. After careful review of anesthetic relateddeaths that have occurred in my practice I know that this can happen evenwhen all reasonable precautions have been taken. If I did not have theadvantage of being able to see this situation from "the other side" I maynever have understood or forgiven the vet involved in my dog's death. Afterreviewing the three cases in which I feel some or even strong responsibilityfor the death of pets in my care for anesthetic procedures I have had tostruggle with forgiveness from a whole different aspect. In the end, weare all human and all that we can do is the best we can do at any giventime. The bad thing is that isn't good enough in a profession such as mine.I am very grateful for the two owners who have forgiven me for the lossof their pets -- and let me know. I am still struggling with the ownerof the third pet. When Hank died, I knew that there was going to be a lotof soul searching on both the owner's and the vet's part. You see, he wasmine. I really do understand the pain of losing a pet because of a medicalprocedure. It has happened to me twice. Despite this, I continue to spayand neuter my pets and I continue to do surgery on them when it seems necessary.The overall benefits exceed the risk.

That is the whole point I am trying to make -- you may very well beright that ivermectin was the trigger for IMHA in your poodle but thatdoesn't mean that the medication's benefits do not outweigh its risks,overall. It is just so damned hard to be one of the persons who suffersdue to the risk.

Mike Richards, DVM

Closure Q: Dr Richards, I just want to thank you for your very understanding letterregarding "Buttons", my toy poodle and the IMHA she contracted. I knowhow very busy you must be and I appreciate your taking the time to addressmy situation.

I intend to send a detailed letter to Merck and I want to build as muchof a case as possible. Would you mind if I used any of the responses thatyou've sent to me over the past several weeks? I promise that I would nottake them out of context...I'm not like that. I do want to come to closurewith this though and get on with my life.

Just to let you know that I don't expect Merck to yank Heartgard fromthe market on my behalf, because I do realize how beneficial it is in preventingmore of another problem from occurring. I do, however, expect some sortof disclaimer or warning on the packaging so people like myself can atleast be aware of the POTENTIAL harm of Ivermectin in some dogs. Thanksagain for listening, and responding, Tom

As an aside to my email...the FDA/CVM does monitor and register allthe REPORTS that come in, under their adverse drug reaction category. Dr.Neal Bateller (sp.) told me that, unfortunately, many of these types ofcases don't get reported for whatever reasons. I know that I have reportedmy situation and another fellow has reported his. They both now appearon their web site under a statistical column, for whatever good it does.Dr. Bateller also said that if enough of this kind of report came in, theywould approach Merck about it. Again, for whatever good that would do.Tom

A: Tom-

I do not have any objection to your use of correspondence from me indiscussions with Merck. I am pretty sure that they are aware of the website,anyway. Michal pointed out to me that I had not sent you one piece of informationfound in previous posts on IMHA. Poodles are one of the breeds consideredto be susceptible to this problem as a naturally occurring phenomenon.This does not change any of the previous information, it just is one morething to consider.

Mike Richards, DVM