Canine Autoimmune Hemolytic Anemia (AIHA & IMHA) - 'one DVMs AIHA protocol'

The following is a protocol sent to me by a supposed authority on AIHA. I have not tried most of this, so cannot comment on how good it is. I would appreciate any comments or contradictions someone may see here. I don't know off top of my head how to convert pound to kilograms, but here is a version of Pred dosing I will check out. At this point in my crisis, I am going with what you guys have been telling me today and up my Pred dose on Pop.-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Here is my protocol for treating IMHA:
Immune-Mediated Hemolytic Anemia

History:

1.. Any History exposure to ticks, travel to tick infested areas?
Test
to rule out Babesia, Ehrlichia, Bartonella, & Rocky Mtn Spotted Fever
as
causes.

2.. On any current meds that could cause anemia, thrombocytopenia?
For
example Sulfatrimethoprim?
3 Has there been any exposure to rat posion? Zinc?

4. Were there any recent vaccines (w/in last one month)?

3.. Any concurrent health problems?
Neoplasia : Hemagiosarcoma, Sertoli cell tumor, lymphoma

Diagnostics: Minimum data base

1.. CBC including platelet count
2.. Check Purple Top Tuibe for autoagglutination, check slide for
autoagglutination, look for sphereocytes, or stomatocytes on the
peripheral
blood smear
3.. Manual differential, cell morphology (regenerative anemia? (30%
of
IMHA are not regenaretive)
4.. Spherocytes (near the feather edge don't count)
5.. Platelet estimate consistent with low count or due to clumping?
6.. Chemistry panel ( Low albumin indicates hemorrhage)
7.. Chest rads & abdominal rads to rule out cancer, pneumonia
8.. Abdominal rads to r/o zinc toxicity (metal FB), cancer, pyometra,
etc.
9.. Abdominal Ultra Sound to check for neoplasia(i.e. dog >7yrs)
10.. Babesia titer if greyhound or travel history, Ehrlichia titer if
also
thrombocytopenic
11.. UA - look for hemoglobinuria
12.. Coag panel and/or ACT if evidence exposure to rodentacides
Treatment: (D/C any current meds!)

1.. Prednisone 2mg/kg PO BID divided; start at same time as Dex SP is

given
2.. +/- Azathioprine 2mg/kg PO SID if not responding to the
prednisolone
3.. Pepsid to prevent gastric ulcers form the Prednisolone
4.. Doxycycline 5 mg/lb bid just in case it is Ehrlichia
*Do not use Cyclosporine, Cytoxin, Oxyglobin - studies show a decreased

survival rate with these drugs

Transfusions:

a.. Better to transfuse sooner than later
b.. Transfuse if PCV<15%
c.. Use Fresh Whole Blood
d.. True universal donor (DEA 1.1, 1.2, 3.5, 5.7 negative) is best as
you
usually can't type or cross-match due to agglut.
Monitoring:

1.. CBC q12hrs
2.. monitor electrolytes q24hrs if on IV fluids
3.. Monitor slide for agglutination q12 - 24hrs
4.. Blood smear daily to look for regeneration, platelets
Sending home:

1.. Prednisone 2mg/kg PO divided BID for at least one month; until
platelet count is above 150,000 or Hct is above 21 and stable. Then
decrease
dose, whenever the blood tests remain stable for two weeks.
2.. Dogs usually require low dose pred for a year.
3.. Azathioprine 2mg/kg PO SID
4.. Pepsid PO while on high dose pred
5.. recheck CBC weekly to start; CBC at 1 week, 3 weeks, and then q2
- 3
months while on Azathioprine
Allison TX


PS - under his #4 on treatment is where I was a bit scared off of the Cyclo... But once again, it's another "opinion"
Thanks to all
Allison TX


Allison,

Don't go by my word alone but.... that all sounds a bit extreme to me and we have now been through this twice. The first time around (5 years ago) it took about 15 minutes for the vet to diagnose April. One look at her gums, inside of her ears, and the whites of her eyes and one blood draw showing a red cell count less than 15 and you have your diagnosis. First time around April was not jaundiced but this time the jaundice was VERY obvious and her urine was even a dark amber to dark brown color. (the accumulated bilirubin) The only treatment that was different this time around was that my vet had me bring her in every morning (I happen to own a business in the same shopping plaza) at which time they would start an IV and run in a liter of fluid throughout the day. The increase in fluids served to flush the accumulation of bilirubin in the liver as well as keeping her hydrated. She did undergo 2 transfusions this time around (only one 5 years ago)but since the relapse on Nov 12th she has had a quick recovery and her PCV is up to 38 as of this past Wednesday. But of the two different vets that have treated her IMHA now neither ever suggested all of the diagnostic tests that you mention. And oh by the way, to convert Kg to pounds multiply by 2.2. But you are correct the proper doage would be 1mg per pound of body weight.

Good luck to you, and I only wish that it wasn't the weekend and you could find a vet who would give you the respect you deserve in this difficult time
Lisa Florida


This is top notch. It has everything on it that I have been studying the last 8 months. It is the ultimate diagnostic panel for rule out. The only thing missing I see is taking a dietary history for items like onions that could cause Heinz Body anemia. Most of this is what I have read in Schalm's Veterinary Hematology textbook. Tick disease are a very important cause of unexplained severe illness, which can include serious anemia. Nice to see this first on the list of rule outs.

Don't be confused by the cyclosporine mention, I believe that is in reference to dogs that have contracted the very serious tick borne disease Ehrlichia. It looks to be part of the same paragraph. In any case Dr. Dodds does recommend it for severe cases, so perhaps this author believes it is not appropriate for moderate cases?

There is some literature to suggest that Oxyglobin has it's own particular problems when used for transfusion in AIHA . Schalm's does recommend the FWB tranfusions whenever possible but they do recommend a cross match. Some of the notes from this text I carried with me *everywhere* for several months:
"Transfuse IMHA: Assume canine pt. is DEA 1.1 neg & administer DEA 1.1 neg RBC. RBC transfusion excellent, bioavailable, source of iron. Cross match.. store segments of donor bag 7 day to investigate reactions."

I also have seen that specialists tend to like their own particular cocktail of drugs, probably from their clinical success with them. Thus Dr. Dodd's protocol is slightly different than this one. An experienced vet will certainly adjust treatments to the patient's condition.

My notes from Schalm's:
"tx. tapered immunosuppresive doses glucocorticoids
unresponsive > cytotoxic agents > cylcophosphamide 50mg 4 days of each week for 4-5m
azathioprine 2mg/kg daily
cyclosporine 15mg/kg daily"

It's really nice to be able to put those notes back in the box of stuff I have collected. I am going to add this too, very nice.
Patrice
Patrice New York State


> how to convert pound to kilograms
My general and unscientific rule of thumb is to just about double the dose when going from kg per body weight to pounds per body weight. 45 kg is about equivalent to 100 lb. The official google version is: 1 kilogram = 2.20462262 pounds
Patrice n


LISA and PATRICE......

Thanks for your input.

LISA-The vet I used for my dogs initial did not go to the above extremes. Like your case, he just looked at the bloodwork and gums, asked if we'd had any ticks, then diagnosed the AIHA. The vet who wrote the above protocol just sent me all that in response to the many answers I was trying to get from him via email. What other meds besides Prednisone did your vet give?

LISA/PATRICE-I am still uncertain on Pred. dose. In the above protocol, the vet says: "Prednisone 2mg/kg PO BID divided; start at same time as Dex SP is given". Using the conversion (thanks Lisa) my approx. 74 lb dog weighs 33.6 kg. Going by what I think above protocol is saying, he should receive a total of about 67.2mg of Pred. (divided into 2 doses) daily. Right?
That would be about 33.6mg 2x a day.

If I dose him as you and most everyone else here are saying is correct, then his 74lbs. would require a 74mg dose, which is not too far from above authors advise...about 36 mg. 2x day.

Sorry this is so long..I'm figuring it out as I type it.... anyway I will conclude that my vet is WAY OFF w/his dose of 40mg total (20mg x2)

Since I have 20mg tabs and 5mg tabs here, I can easily give 30, 35 or even 40mg 2x daily. I will weigh to be sure in am. If he is about that 74lbs, would it be better to go toward the 70mg dose or push towards 80mg per day?

And what is this "Dex SP" he mentions?

PATRICE - So you think cyclo is safe? At this point I will be cautious. I am not certain my vet ever did an actual test to confirm or deny a tick disease. The dogs did have a few ticks, but vet thought our location would rule out some of those diseases. Do you think the reason he gave him that whooping 3000mg daily for 10 days dose of Tetracycline is a hint he may have a suspicion of something like that as a possibility?

I'm going to take everyones advise and take him to another vet on Monday. He's stabilized for now...still eats, is somwhat alert, will hold his headup, get up to urinate, etc.

THANKS AGAIN!
Allison TX


Hi again Allison,

Keep in mind that this last go round was a relapse after a 5 year remission. When I brought April in to the vet on Nov 12th her PCV was 8. She was immediately transfused with whole blood obtained from the greyhound belonging to the vet tech. She had a catheter put into her leg (that alone was a challenge as she had no blood pressure, virtually no blood and was severely dehydrated) and was started on IV fluids. She was given 20mg of Pred per day divided into 2 doses, 12 hours apart, started on Doxycycline because her WBC's were off the charts, and started on Azathioprine as well as Misoprostol (for stomach upset). She spent about 6 hours per day at the vets office for the next week and half each day receiving IV fluids to fludh her system. After the first transfusion her PCV went up to 20 but she remained weak and on the 20th her PCV had dropped again. Bu this time the vet had discontinued the Doxycycline thinking that it was best to allow her body to battle one thing at a time and he was concerned about over medicating her. She received a type specific transfusion on the night of the 20th and was the only night she was away from us. After that transfusion her PCV came up to 30 and only dropped 2 points over the next two days. She ate for the first time in 2 weeks on Thanksgiving night, but only a few bites. 6 Days following the second transfusion her PCV came up to 33 and I knew we were on the road to recovery. On Wednesday when her PCV was at 38 her Pred was reduced, and the Azathioprine was discontinued. She continues to recover albeit slowly but each day has a little more energy, eats a little more food than the day before, etc...

I agree with you regarding the Pred dosing and would lean toward the 30mg 2x a day. You should be careful not to overdo it as Pred can be toxic. And just so you know April did recover fully 5 years ago just as quickly and was on nothing more than Prednisone after one synthetic transfusion. It takes time and patience and a lot of sleepness nights but I believe you can get through this as Popeye still has an appetite and still gets up to go pee. April literally could not walk on Nov 12th and now she is back to barking at the neighbors and going out on her own (instead of me carrying her) but she does get very tired very quickly so I just let her rest most of the time.
Lisa Florida


Thanks guys! Goodnight.
Allison TX


Schalms Veterinary Hematology states in chapter 118 Immune Mediated Hemolytic Anemia:
"The first line approach to therapy for canine AIHA involves the use of tapered immunosuppressive doses of glucocorticoids (eg prednisolone commencing at 2 to 4 mg/kg daily) In dogs that have severe, acute onset intravascular hemolysis, or with acquired PRCA (pure red cell anemia), or with anemia that is unresponsive to glucocorticoid, the addition of cytoxic agents (eg cyclophosphamide 50mg/m2 orally for the first 4 days of each week for 4 to 5 months only; azathioprine commencing at 2mg/kg daily) to the regime is indicated. A recent study has questioned the efficacy of cyclophosphamide in therapy for AIHA."

In the next paragraph:
"....Cyclosporine (15mg/kg orally per day) is efficacious in the therapy of AIHA but is costly.

74 lb dog weighs 33.6 kg:
2mg/kg daily would be 33.6 x 2 = 67.2/2 = 33.6mg pred twice/day
4mg/kg daily would be 33.6 x 4 = 134.4 = 67.2mg pred twice/day

So your vet recommended 40mg per day? I am not a vet so I can't advise you directly, but it looks the range in this textbook is higher, by 27 mg on the low end and by 94 mg on the high end. Can you connect with another specialist? Or would you feel comfortable contacting Dr. Dodds? Search our archives for her contact information. We started Chance (100 lb) at 40mg per day but in one week (unresponsive) we were asked to bump up to 80mg per day. We remained at 80mg for over a month. That would be at the very low end of this recommendation.

po = by mouth orally
BID = twice a day

DEX SP = "Dexamethasone is a synthetic corticosteroid with approximately 25 times the anti-inflammatory potency of naturally occurring cortisol. Corticosteroids such as dexamethasone are important in normal protein, carbohydrate, and fat metabolism and for their role in controlling inflammation. These drugs have both strong beneficial effects and a definite potential to cause negative side effects. Dexamethasone is commonly used in both small and large animal veterinary medicine. It may be given by injection, inhalation, orally or topically. Preparations for topical use may include other active ingredients such as antibiotics, antifungals, or miticides."

Honestly, this is the first time I have seen this drug mentioned in reference to canines. Schalm's briefly mentions it as a very successful treatment for AIHA for equine and cattle.

Allison, cyclosporine saved Chance's life so I have a very positive reaction to it. On the other hand it made Josh's Sway so sick that she hardly survived it. This is where it comes down to the clinical experience of the vet you are working with. I can't advise you what to do. If your treatment protocol begins to show that it isn't working, then you have to find something else to add to the prednisone. There are a variety of drugs mentioned on this list. I have seen pluses and minuses mentioned with them. It's the skill of the attending vet that makes the difference.

If it were me, yes I would see another vet. I would ask for a IDEXX Snap4dx test for tick and heartworm. If there is any chance there might have been a tick bite, it needs to be ruled out. This is a good in house test that is fast and inexpensive. It doesn't cover all tick diseases, but it is a good start and is highly regarded.
Good luck
patrice
Patrice New York State


Allison-
My vet has done essentially what you've outlined in your post. He never scripted the cyclosporine, but has scripted what I've listed below...

Bella went in for weekly blood work on Friday. Her PCV dropped from 30 to 28. Her retics were 4.5.

We are in week 9 and it seems like she's not making much progress. Our vet is getting worried that if she doesn't hit her turn around quick, things could go from bad to worse, and quickly.

He began a scrip for Doxycycline Friday and indicated that it would likely take two weeks to notice any effects, if any were to be noted.

I'm lost now. He mentioned the possibility of a teaching school, which our nearest would be NC State in Raleigh, NC. He also noted that he was aware fo experimental testing, which I will not allow, so that was quickly ruled out.

I know that many of you here have been waiting longer than our nine weeks, but knowing that she's on such a high dose of pred also makes me worry a little. She's blown up like a tick right now.. Gained a few pounds, maybe two, but looks really swollen. At times, she seems energetic, but it only lasts for a few minutes at best, then it's back to normal and she's resting.

I don't understand how she can look like she's doing so much better on the outside, when the inside is really not that much better off than it was 7-8 weeks ago.

Bella is currently on Pred - 15mg, azathioprine (unsure of dosage) and famitodine (Pepcid AC), and now Doxycyline (again, unsure of the dosage as I had to leave town for work and the wife is administering it)

She's a Peke who is five years old and weighs 20lbs now. She was at 17 or so prior.

I don't know how the rest of you battle this ride. My heart is saying one thing, logic is telling me otherwise. I can't imagine coming home and not seeing Bella at the door, buut I hate seeing her in the shape she's in now, knowing what she was like prior of this damned disease....
Jason Myrtle Beach


Jason,

I did not have a vet who would follow the protocol advice that I've posted above. My dog had his first AIHA about 12 days after his boosters in Oct. He seemed to recover, but has since relapsed. The only "from experience" thing I can say that seemed to help him in the initial crisis was a drug my vet added at a very low point for the dog. He basically had just told me the dog was going to die, because his organs were shutting down. He gave him a drug called Denosyl. About 36 hours after that, he made remarkable inprovements. Don't know if that is what did it or it was a coincidence.... If you google the name of med, their ad comes up.
Allison TX


Denosyl is in essence just Sam-e, a popular over the counter supplement that many people use as a mood enhancer, to ease pain in joints and support the liver. I used a veterinary product called Denamarin which is a combination of Sam-e and the essense of milk thistle called silybin.

Now that the crisis is over in our household and Chance's liver enzymes are closer to normal I am just buying Sam-e and Liver Support Factors (Country Life) (which contains milk thistle) and giving them to Chance instead. They provide excellent liver support for a lot less money. The Denamarin was very expensive. I can get Sam-e And Liver Support Factors at Vitacost for a very reasonable price. This is one way that owners can save a lot of money on supportive care for their dogs.
Patrice
Patrice New York State


Patrice, Thank you for your information on Sam-e and Liver Support Factors. We have been giving Denamarin to our Lhasa Apso mix for the past 2 months. He is medium sized, and the vet charges $47.00 per month for the Denamarin.

I plan to check the products that you mentioned - hopefully, we will be able to use them and save some money.

Sue
Sue PA


Sue,
Look on the back of your Denamarin package and match the exact dosage listed for the Sam-e. I am using 400mg. You can get a smaller dosages of 200mg if you need. http://www.vitacost.com/NSI-SAM-e

The Liver Support Factors by Country Life only comes in one size and two of them is equivalent to the milk thistle dose that Chance had been getting in the Denamarin (2 tabs has silymarin equal to 98 mg). You could probably cut it in half if you needed to. This product was recommended by the tick-l discussion group I am on. It has literally saved many dog's livers. http://www.vitacost.com/Country-Life-Liver-Support-Factors

I do not benefit from this mention of these products.
Patrice
Patrice New York State


Patrice,
Do you find the Sam-e helps with joint pain? I am using plain milk thistle, does the liver support factor do a better job? Thanks!
Wendy Florida


Allison,

I just found this site today, and read most of your threads. After reading about your experiences, I feel extra grateful for my vet. What you've posted here seems to be similar to what he did for Lola. Here's the Reader's Digest version of my experience--

• I brought my 2-year old Aussie Lola to the Vet on Labor Day, and they diagnosed her in about two seconds, but they did a bunch of tests anyway. (Grateful to Banfield for being open on a holiday so I didn't have to refinance my house!)

• We started her on 30mg of Prednisone and Doxycycline in case it was a tick.

• She was on 30mg of Prednisone for 4 weeks (she weighed 34 pounds at the time (I can't remember when we stopped the Doxycyline).

• Weeks 5 and 6 we tappered off the Pred., but her numbers slipped, so we added Azathoriprine.

• Her numbers jumped big at first with Azathoriprine (weeks 7 and 8), but declined slightly after reducing dosage from 1/2 pill to 1/4 pill (weeks, 9, 10, 11).

• Currently (weeks 12-15) we're on 10mg of Pred and 1/4 pill of Azathoriprine and we'll see where we are at in a week and a half.

Best to you and your pooch, Pop!

Connie
Connie St. Paul


Allison,
Just found this site today. I am taking my boy Jack to the vet tomorrow with pale gums and loss of appetite. He acts like he doesn't feel good at all. He started this about a week ago. I don't know why, but I checked his gums today and saw how pale they were. He had his shots on Nov. 7th.
I can't get to the vet fast enough.

How is Pop?
Lisa Austin


Wendy wrote: Do you find the Sam-e helps with joint pain? I am using plain milk thistle, does the liver support factor do a better job? Thanks!

Hi Wendy,
Wait.. let me ask Chance how his joints feel. :-) I don't really know if it does or not. The problem, as always, with over the counter stuff is that most of the information is anecdotal. The FDA doesn't get involved with studies on otc supplements. However, some of the anecdotal stuff I have read and the few small studies about Sam-e I have seen really show a benefit to the liver. Dr. Dodd recommended it to me early on, so I found that helpful. I did find a couple of papers on line in reference to canine liver support and they were positive.

Now, for milk thistle vs Liver Support Factors, same deal, it's mostly anecdotal information. I found it while reading the tick-l discussion group I am on. It was mentioned over and over as the one thing that was helping drop the liver enzymes while dogs were being treated with extremely high doses of doxycycline. As a matter of fact, one of our great researchers on the list, Gil Ash, has developed a whole web site devoted to tick diseases, diagnosis and treatments. She has a whole page devoted to Liver Support Factors! So go here and read about how successful LSF has been for so many people.
Patrice

http://dogsandtickdisease.googlepages.com/liversupport
Patrice New York State


Wendy,
Now that I look at Gil's page, I see that she has the ingredient listing on there. There are a few things that stick out to me that are very beneficial. Taurine and alpha-lipoic acid are good for the heart. Licorice extract has been reported as a good support for the thyroid which is important in body regulations including blood manufacture. The two enzymes listed are helpful with digestion. You could do a google search on the rest. Patrice
Patrice New York State


Thanks Patrice for your answer; I have ordered the Liver Support, it is very reasonable and seems to have helped many dogs.

TC has arthritis and as we decreased the pred he really had a problem getting up and down, I have to help lift him in & out of my SUV when we go for a blood check.

I started him on Cetyl-M and he is doing much better, but nowhere near where he was before he became ill. My Vet mentioned putting him on a med for the arthritis when he is off the pred, but I am not sure I want to compromise his liver more than it already is.

Thanks for the info,it is really appreciated!
Wendy Florida


Wendy.
You are welcome. It is reasonablely priced!

I am doing a small experiment at home with Chance and I. We have both been taking a Country Life glucosamine and chondroiton product called Arthro-Joint & Muscle Relief Factors to see if it relieves joint and muscle pain. Since I KNOW I am taking it, it kind of throws off the whole thing, but Chance certainly has no idea what he is taking. So far he is bouncing around like a puppy, going on two hour walks with Daddy twice a week and taking 45 min walks 2 times a day. Now it could be because he is just plain getting better, who knows?

However, I have worked with the Arthritis Foundation part time for over 20 years teaching water exercise therapy classes to seniors. I have asked them periodically about glucosamine use. Many have responded that they use it regularly, their doctors told them to use it and some claim it works really well to relieve pain. I attended a seminar about 1 year ago for medical professionals on arthritis and the physician presenting did a component on over the counter meds and supplements. Glucosamine was included and they recommended a dosage for pain relief.

So it is commonly used by Americans. Even Consumer Reports did an article on it. They recommended using quality formulations, avoiding places like the dollar store etc. I can't remember all the details. But worth looking up.
Patrice
Patrice New York State


This thread was discussed between 02/12/2007 and 06/12/2007

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