Canine Autoimmune Hemolytic Anemia (AIHA & IMHA) - Hi -- My pup Bentley just diagnosed

Hi, everyone,

I am so happy to have found this group. Our 7 yr old Pomeranian recently had double knee surgery for patellar fluxation. Two weeks after surgery, he began having what appeared to be "fainting spells", which I now know were episodes of syncope. Blood work showed anemia, with PCV of 19. This happened quite suddenly, as his pre-surgery numbers were all within normal range.

Bentley received a blood transfusion and had lots of tests (including check of bone marrow). The vets believe this is IMHA....he has been prescribed Doxycycline (in case of a tick disease), Prednisone, and Cyclosporine.

Two days after the transfusion, his PCV was 24....today (one week later) it was 23 :( I was hoping for better, but am beginning to understand just what a complicated illness we are facing. Bentley does seem to be feeling better....his appetite is much better (steroids, I'm sure) and the syncope has stopped. I do see the heavy breathing still...will keep a close eye on that. We go back next week for blood recheck and maybe meds adjustment.

I'll be reading, reading, reading, and learning from you all....I'm so glad to have folks I can ask questions of!

Nice to meet everyone :)
Sally Louisiana


Hi Sally,

Like I said to Kelly, I am happy you were able to find us here, but sorry that you had to. I certainly wish you the best in your fight and will try to help where I can.

Heavy breathing is necessary as prednisone stimuates metabolic activity and generates heat. Of course there can be anemia, or other issues that create panting so you are right to keep an eye on it.

I know you probably red this on Kelly's thread, but:

Stomach protectant is a must. Prednisone, Cyclosporine and aspirin are hard on the stomach. Pepcic AC (famotidine) at the least and many recommend sucralfate (brand?) or similar stomach protectant to bind to ulcers if they occur. And long term use of these drugs makes that likely at some point.

Everyone will agree, enlist Dr. Dodd's experitse. She really cares about all dogs and always helps.

Pet Tinic is a supplement of Iron and Vitamin B for building red blood cells and hemoglobin. I bought mine online, but some vets cary this. There is also the liver that can have issues processing the drugs, destroyed red blood cells and higher intake of food thanks the prednisone. Most recommend Milk Thistle, or denmarin (sp?) - I am sure someone else can speak to these.

It will help if we also know more about your dog - weight, overall health, any health issues, weight, skin, behavior etc.

Knowing your exact doses and frequency of the drugs taken. More info will help those here provide better advice.

Blood work results. Get the results from your vet and post them. There are people here who can help you interpret them. This can help for both short term and long term care.

Fingers crossed, praying :-)

Richard and Dylan
Richard Burnaby


Richard,

Thanks so much for the reply! I should have mentioned, Bentley is already on Pepcid A/C to help prevent GI issues....He takes 1/4 tablet twice a day currently.

Mr. B has been a very healthy pup, 7 yrs old, happy disposition, with two other pups and two cats as housemates. He just had his knee surgery last month, and came through that just fine. He weighs 11 pounds.....current meds, in addition to Pepcid, are:

Prednisone 10 mg twice daily (started 6/30/11)
Doxycycline 1 mL twice daily for 14 days (in case of tick borne disease) (started 6/30/11)
Cycolsporine 25 mg once a day....this med was just added today..... (started 7/7/11)

His bone marrow tests did show the marrow was producing new cells....I'm going to get all his lab results as quickly as I can (hopefully tomorrow) and post them....Then I can also begin the process of contacting Dr. Dodd.

Again, thank you so much for your response. I'm just realizing what a road ahead we have here. Good to know I can get some directions. (I suffer from fibromyalgia, and try to help newbies on my fibro board....another long road!)

Thanks for the prayers!

Sally

Sally Louisiana


Sally,
Sorry that Bentley has been diagnosed with this awful disease. You have found a wonderful place for support and answers. It is indeed a roller coaster ride but everyone here knows and understands what you are going through. I dont't know if you found Joanne's site but here is a link just in case. It will answers a lot of your questions.
http://www.cloudnet.com/~jdickson/
Penny
Penny Lytle Creek Calif


Sally, get a copy of the pre-surgery bloodwork as well. This sounds to me like it's surgery related...drugs, stress, etc. Tell us all you can about the surgery...drugs taken...etc. Often times they'll say bloodwork is all normal when in fact it may not be. I'd look at them just to be certain....if i were you.
How's Bentley doing today? Responding to meds?

Lots of thoughts, prayers and healing vibes for Bentley.
Johnny & Tessy

Johnny


Hey, guys.....Sorry I haven't checked in sooner. It has been a busy few days with Bentley.

Unfortunately, the news has not been good. His numbers have not improved, and it has become apparent that his platelets are decreasing too....so we are facing Evans Syndrome. He is classified as non-regenerative now....

Here's a summary of bloodwork:

(Pre-surg) At LSU At LSU At LSU our vet our vet/LSU our vet
5-26-11 6-29-11 7-1-11 7-7-11 7-9-11 7-11-11 7-13-11
RBC / Erythrocyte 6.74 2.17 2.99 3.18 3.14 3.05 2.59
Hemoglobin 11.1 4.9 6.7 7.6 7.0 6.9 7.0
Hematocrit 39.27 15.9 21.7 22.9 22.45 21.69 18.71
Platelets 438 199 197 589 477 385 274
Absolute Retics Not Avail 45.9 52.0 87.9 75
Advia Retic % Not Avail 2.1 1.7 2.8
Total WBC’s Not Avail 9.1 16.8 30.3 26.72 39.36 35.42

His blood transfusion was on 6-29-11. He started Pred 10 mg 2x/day on 6-30 and Cyclo 25 mg 1x/day on 7-7. Today (7-13) vets upped the cyclo to 25 mg 2x/day in hopes of stopping this downward spiral....He will also go for a B12 shot tomorrow, and recheck blood Friday....We also started Milk Thistle/SamE and Pet Tinic....

Today's news was sombering....hope we turn a corner soon....

Any thoughts or advice would be welcomed.

Thanks,
Sally
Sally Louisiana


Hi Sally,

Don't give up hope. It's good that they increased the cyclosporine to 2x a day. Make sure it's the name brand and not a generic one....the docs seem to think the generic wasn't working as well. Daphne has been through 3 transfusions. I really didn't know what to expect, but things seem to be going in the right direction. It's taken almost 7 weeks to get there with some major bumps in the road. What I learned most from this whole forum is to stay positive. Especially when you are with your baby. They can pick up on us so much. I talk to Daphne all the time, telling her how healthy she is and how proud of her, etc. I keep telling her to fight and that I will fight with her. Sounds crazy, but not only do I feel better, she is as well. She knows I'm pushing for her.
The meds seem somewhat the same. Only difference is that Daphne is on prednisone 5mg 2x a day. They also have her on 2ml of liquid aspirin in case of clots.
Not sure what else I can add, but I am here for you. I am learning as I go along, but it helps to have others who are going through the same thing.

Stay Strong

Hugs,
Kelly
Kelly Mass


Thanks so much Kelly! I had those numbers all typed in a nice chart....hate that they came out all jumbled up :(

Basically, he had a little upswing just after his transfusion, and since 7-7, numbers have gone down. I'm hoping med increase will bump him up. We may be looking at another transfusion too....

I hope Daphne's improving as well....And please know I am here for you too! You're right, it does help to have others to talk with who are going through this and understand.

HUGS from down south :)
Sally

Sally Louisiana


Sally,
I am so sorry your Pom is going through this. My dog had syncopes later in life and I sympathize with you about how awful they are to watch.

A quick look at your numbers shows the first set done pre-surgery are all within normal limits. Can you tell me if they performed a blood transfusion during the surgery? And if so can you tell me the source of the blood they used? I would also like to know if they have carefully listened to the heart post surgical.

Anemia is actually defined by most human blood authorities (like the Red Cross) as a deficiency in hemoglobin and that is the measure they use when determining whether a donor can donate or not. You can see that there was a very fast decline in one month from 11.1 to 4.9. However there is somewhat of a recovery a few days later to 6.7. But then it just hovers, nearly stationary. Why?

Some of the other values bear out the same trend. Normal numbers followed by a speedy decline and then a slight increase that plateaus over several of the values.

There is a mild response by the bone marrow as indicated by the Absolute Reticulocytes. These numbers are read as 45,900 to current 75,000. (There was no pre-surgical value.) These cells are baby blood cells that are made in the marrow every day as our old red blood cells age and are replaced. So in a normal human or dog without anemia, the number in the blood should be around 60,000 or 1%.

In response to a condition of low amounts of oxygen being carried by red blood cells to body cells, the marrow will begin to produce more reticulocytes and put them into circulation early in hopes of providing that needed oxygen. They normally mature in the marrow so when they are seen in the blood they still contain their RNA, which makes them larger than normal RBC and thus easy to identify.

With a hematocrit of 18.71, there should be a much larger response than 75,000 reticulocytes even though the bone marrow test indicated there was a response. This number should be upwards of 150,000-300,000 for a short period of time until they mature into red blood cells. We are not seeing that happen, in fact these numbers look sluggish. This may classify this as non regenerative anemia regardless of the bone marrow biopsy. At least it classifies it as a very mild regenerative response.

There is also a rapid increase in the total number of white blood cells. This isn't broken down into types so its hard to say what is going on here. But I feel that this may be the key to what is happening. Did they discuss giving any antibiotics at this point? Have they tested for infections like urinary tract infection? Are the surgical sites well healed?

They are correct to treat for a possible tick disease. Doxycycline is the antibiotic for this and it can be very hard on a dog's stomach. You may see some inappetance because of that. However, this drug isn't the best for general infections.

The B12 shots are an effort to provide a needed vitamin to the bone marrow in hopes that this sluggish reticulocyte production will be stimulated. It is completely harmless and you can easily learn to give these shots at home. Have them show you how to do this.

I also feel that you should talk to Dr. Dodds about supplementation with the thyroid medication Soloxine. She is the expert here on this and does often recommend this to stimulate the bone marrow in cases like this. It does not necessarily mean there is anything wrong with the thyroid at this time, but testing would show that one way or the other.

I hope that you can find out the answers to some of these questions from your vet and Dr. Dodds. Please post them when you are able
my best
patrice

Patrice NYS


Hi Sally,

Hang in there. I don't know much yet about the dfferences between non-regenerative and regenerative (other than the body is making reticulocytes/rbc's in regenerative). I am sure some more experienced people will offer some info when they can. Sometimes the response to the drugs takes longer. Each dog is different.

Dr. Dodds is a good choice for advice when there are difficult choices, or things don't seem to be working.

One thing that I find important is to try and see any other signs of behavior that indicate sensitivity to prednisone or the other drugs (look for side effects for oversensitivity), or whether you are seeing any effect. I could see Dylan's cycle of anemia stop and turn positive after she went somewhere below 10. She was so weak, I was afraid to move her, but after thinking for sure I was losing her, she started to show positive signs and started slowly getting stronger every day. It was easy to see her stand up and walk and go for a pee etc, which she could not do when at her worst.

There are a lot of side effects and over-reactivity can mean prednisone is inhibiting recovery along with inhibiting the immune sysem. On the other hand, low sensitivity would mean more prednisone, might be necessary. 2 mg/pund/day (Split in 2) was a lot for Dylan. I could see serious aggression and immediate demand for food. I also began to see muscle loss quickly.

Check out this link on Iatrogenic Hyperadrenocorticism, which is a form of Cushings Disease caused by coriticosteroids like prednisone. Depending one what you see for water consumption, aggression etc., you might be able to determine if you see predniosone working and how reactive your dog is to it. In Dylan's case, she was more reactive and despite seeing a good initial recovery (39 10 days after being at 10 and no transfusion), we saw a steady decline in pcv after that due to prednisone. Her pcv is now 42 (celebrating today), 1 week off prednisone and I am convinced it will continue to climb as even low dose prednisone can inhibit rbc production.

http://www.kateconnick.com/library/cushingsdisease.html

But as I said, I used behavioral signs to tell she was very reactive and I reduced her prednisone after 4 days and then 10 days later because I could see that her reaction to prednisone was strong. I was worried right away that it would impact her recovery negatively and as a result. We never did add any other drugs as we could see prednisone wworking in her body after 4 days.

If I did not see the behavioral signs, maybe increased drinking, but not excessive (Dylan was constantly drinking, except whe so anemic I had to use a syringe), maybe a little panting, but no muscle loss (the head is the most obvious place) and no, or very little aggression. Then I might think Bentley is not very reactive, so I would not likely consider dropping the dose and might consider an increase (although I prefer not to give too much, prednisone is very hard on the body too). I would never have considered increasing prednisone in Dylan and in fact dropped it while her pcv was about 10-15 due to the behavior I saw.

Dylan's photo diary shows what prednisone looks like after 4 weeks in her. The speed of this surprised my vet a bit and she is pretty experienced with the disease. The video of her anemia shows some muscle loss already after only 7 days.

I really hope you begin to see positive signs of recovery soon, Good Luck!

Richard and Dylan
Richard Burnaby


Patrice and Richard,

Thanks so much for responding! I'll try to answer all your questions as best I can....

@Patrice....Pre-surgery, Bentley was fine, numbers looked good...he didn't receive blood during surgery. He had a regular checkup the week of 6-22, and seemed fine.... when our regular vets listened to his heart beginning 6-29, they heard a very low grade murmur due to the anemia. Bentley had a blood transfusion on the evening of 6-29, which is the reason for the increase in his numbers....the last few days, he has begun the downward trend.

Your comments on the Reticulocytes mirror the vets' exactly....Our LSU consultant does in fact consider him now (at 75000) to be nonregenerative, even though his bone marrow test showed new cells being formed....he is soooo sluggish, and his low numbers do not match up to the typical IMHA pattern. Yet the bone marrow test showed no sign of bone cancer or other issue....

His white count has gone up and down....the LSU vet feels this is from inflammation due to the IMHA....his surgical sites are well healed, and he shows no signs of any other infection, but I will ask tomorrow about UTIs, and possibly adding another antibiotic.
Here's a quick summary of the breakdown over time:
LY 2.57, 2.5, 2.9, 1.8, 3.01, 3.83
MON 0.45, 0.6, 1.8, 1.7, 1.13, 1.16
NEU 8.62, 5.5, 11.9, 26.8, 22.32, 33.97

So neutrophils are going up, monocytes are going up, lymphocytes also still going up a bit....others (EOS, BAS, Bands) minor changes.

I am emailing Dr. Dodds today....have just finished putting Mr. B's results in a spreadsheet so they are easier to read, so I can send them to her.

@Richard, I'm not seeing the signs from Bentley that he is overly sensitive to the pred....he is drinking a bit more than usual, but not too much. Appetite is good, but not unreasonable. He has shown no signs of aggression to me or his housemates. I don't see any muscle loss on his head....a bit on his legs, maybe, but then he just had double knee surgery too, so hard to tell there. So for now, I think we keep the pred as is....but it is good to know the signs to look for!!

Thank you both soooo much for your help....I can't tell you how much it means to me and Mr. B. We go back in the morning for another CBC, and to see if we have to head back to LSU....

Sally

Sally Louisiana


Sally,
Thank you for filling in the blanks for some of my questions. I appreciate the time it takes to organize it all into something readable.

I was concerned about any blood transfusion that might have been done during surgery. I am on a list that discusses ticks and apparently there has been an increase in blood transfusions passing on tick diseases in dogs.

I felt that there might be a murmur. It is possible, at 7 yrs old, that a Pom can have a slight murmur from a leaky valve. In layman's terms this generally means that the heart has a bit harder time pushing all the freshly oxygenated blood out of the heart into circulation. Some of it doesn't make it out of the left ventricle because the mitral valve is leaky and it backwashes up into the left atrium. The anesthesia used during surgery can slightly worsen this condition even if great care is taken. It is one reason surgery is not risk free for dogs or humans. Dogs cannot have their mitral valve repaired like humans can. So it is a one-way street. I know this because my dog had a mitral valve murmur and he had syncopes which worsened over time in frequency.

I am not relieved that I was correct about the reticulocytes. This is the same condition my dog had, non-regenerative anemia, and these test values bring back a painful memory of Chance's tests. With Dr. Dodds help I was able to save Chance's life though it was a complex treatment protocol. So I do advise you to contact her, ask for her help and trust what she says. Whether your vet will agree to follow her advice is questionable. Some academics don't have a positive view of her research and treatment protocols. My vet was surprised and delighted to consult with her, feeling she is a very well known veterinary doctor with expertise in the thyroid, vaccinations and blood diseases. With my local vet's help we were able to do most treatments in their office and I did the nursing care at home.

Thank you for showing the results of the generalized white blood cell increase. A slight increase in eosinophils may be of some importance. These white blood cells are very rarely seen in blood samples so any number at all is significant. They are associated with two things. Parasitic infections and generalized inflammation from allergic reactions. We see eosinophils increase in some, but not all, dogs with serious tick diseases. Have they done a full tick panel that matches the types of tick diseases prominent in your area? (And have you traveled at all to other locations in the past 6 months?) There are some tick diseases that can cause these specific signs and symptoms that you are seeing.

There is a condition called Anemia of Chronic Disease or Anemia of Inflammatory Response. The theory behind this is that the body, when faced with some inflammatory, autoimmune or malignant condition will down-regulates iron manufacture and this can impact blood manufacture and lead to a moderate anemia. This can eventually lead to a non-regenerative anemia.

New research is showing that the body will reduce the metabolism of iron in an effort to inhibit the growth of something like a bacteria (that need iron to grow and reproduce). It will then greatly increase the numbers of white blood cells to fight the infection. This is the inflammatory response. The downside of this is that the thyroid will also reduce its output and hypothyroidism will follow. In addition, this inhibition of iron production has a direct negative impact to the making of red blood cells in the bone marrow.

Blood production in impaired by low available iron and little stimulation to the organs involved in this process (such as the kidneys). Attempting to supplement with iron nutritionally may not be entirely successful because of the mechanism of how iron is inhibited.

If you have been able to follow what I am writing, there is a possibility that this is what is happening to Mr. B. What is the solution? Obviously, resolving the underlying condition is the answer, if you know what that is. But Dr. Dodds will sometimes suggest treating with Soloxine in an effort to stimulate the bone marrow.

You are reaching a point now where the prednisone has been administered for a relatively long time (nearly one month, correct?) The side effects will become more pronounced. Please read about Iatrogenic Cushings Disease so you know the range of things that are happening. Look for the section titled Iatrogenic Cushings Disease.
http://www.kateconnick.com/library/cushingsdisease.html
The side effects can seem as bad or even worse than the condition of anemia. Chance was in very poor shape after nearly 2 months of prednisone. Thankfully, Dr. Dodds intervened at that time and told me I needed to get that dosage down immediately and start using a new drug, cyclosporine.

One more thing, will you ask your vet if they have seen spherocytes in the blood smear? This would help indicate if there is any autoimmune destruction of RBC still occurring. These are damaged red blood cells that have a particular shape. I am guessing that they are not seeing these now.
my best
patrice
Patrice NYS


Patrice,

Thank YOU for all the time and effort you are giving to me and Mr. B....I cannot tell you how much it means to me!!

About two months ago, I found two dead ticks on Bentley...we use topical flea and tick prevention, and do go camping in nearby parks....I told all the vets involved about this. They so far have not done the tests, but have put him on Doxycycline since 6-30-11 to cover any tick infection. Do you think I should insist on this panel at this point? (He is still taking this antibiotic.)

I think I am following (somewhat) the Anemia of Inflammatory Response, and that does seem to follow his path. I did email Dr. Dodds earlier today, and she has already answered...WOW!....unfortunately, she was unable to open my attached file of Bentley's numbers (I have no idea why it wouldn't work), but I replied to her and typed his counts out in the new email. She liked the meds he was on now, and suggested putting him on Thyroxine to help stimulate the bone marrow.

UPDATE: She thinks it was likely the vaccines, especially given so close to the possible stressor of the surgery, that caused Mr. B's problems. ***SIGH*** I thought I was doing the right thing, making sure he had all his vaccinations........

He has been on Prednisone for 2 weeks (started 6-30-11) and Cyclosporine 1 week (7-7-11)...but numbers have not responded to either. I will definitely look at the info on Iatrongenic Cushings Disease to learn about the side effects. We just upped his dosage of Cyclo, so we are hoping against hope that it will "kick in" in a few days.

I expect us to be at LSU tomorrow for blood work...I'll definitely ask about the spherocytes. While I was giving him his meds tonight, Bentley had another episode of syncope with voiding....maybe even a bit of paddling of legs. It only lasted a few seconds, and I called our vet. We decided to talk more in the morning, and then I'll take him to LSU for blood work.

I'll update when I know more.....Thank you again SO MUCH!!

Sally and Bentley

Sally Louisiana


Hi Sally,

Sorry you still have not seen improvement, but hang in there. I am not surprised either when it comes to vaccines, they do cause AIHA and other problems, but the propaganda is so strong and some vets swear they are 100% safe. I would leave any vet who does not know and warn me about the risks and I know many dogs who have had seizures and other issues as a result of vaccines. I vaccinate very carefullly now. Dr. Dodds has written a fair bit on vaccinations and has developed a new protocol she suggests we follow with our dogs. Search her name with vaccinations and you should find it.

Don't punish yourself over any choices you have made. Dylan and many others get this disease without a vaccination. But believe me, the drug companies promote them as safe although they have plenty of risk we should be warned about prior to haviung them given. They are not tested like other drugs either and the companies that produce them are protected from being sued; no sick dogs, no dogs tested while taking anaesteics or other drugs for interactions.

You cannot have known this and you obviously are always trying to do your best for Bentley. That is all you can do. If anything, it is the experts who promote vaccines(vets)and "push" them without concern for what they can realy do that are the problem. Again that won't hep Bentley and neither will punishing yourself.

You are doing the best you can, keep it up, you are doing a great job. Bentley needs your continued strength and I and the others here will support you all the way!!!

Go Sally! Go Bentley, big big hugs to you both,

Richard and Dylan

Richard Burnab


Richard,

Thank you so much for your kind words of support. I'm trying not to "beat myself up" over this....I didn't know vaccines could possibly be linked to a reaction of this sort. In all my years of having dogs, I've never had one react poorly to annual boosters, or develop IMHA. Guess I'm just doing the "coulda, woulda, shoulda" thing....just wish we had waited a bit on his vaccinations. But it is done, and now I just try to help Mr. B.

This has definitely been a learning experience, and I hope some good can come of that. It puts me in a position to help someone down the road like you guys have helped me, should anyone I know find their pet diagnosed with this horrific illness.

I'll post more about Mr. B later today....he had a quiet, sleepy night, and is very lethargic this morning. I fully expect numbers to be down again. We see our vet at 9:30.

Thanks so much,
Sally
Sally Louisiana


Update on Mr. B:

Well, he was down just a bit this morning....HCT was 17, and very listless. With the syncope beginning again, our vet sent us back to LSU. They will do another transfusion tonight, and will probably tweak his meds. Latest CBC does show his Absol Retic to be 115,000, up from 87,500, so that is a plus!!

Hoping he can come home in the morning, if all goes well tonight. Saying our prayers!

Will update as I hear more.

Sally
Sally Louisiana


UPDATE: Just got a call from LSU....Mr. B is doing fine mid-way through the transfusion. He is sitting up in the cage, and even "fussing" at the techs tonight! Hopefully getting a bit of his spirit back :)
Sally Louisiana


Great news Sally! The key is -- baby steps! And hopefully these baby steps turn into leaps and bounds soon!

Hang in there!

Sharon
Sharon PA


UPDATE: Mr. B was able to come home this morning! The only hiccup was one episode of vomiting with a tiny bit of blood....the internist feels sure it is due to GI upset, so put him on Sucralfate in addition to his Pepcid to help the belly.

He only needed partial transfusion, and his PCV is up to 35! Hopefully that will buy him time to give the tweaked meds a chance to kick in. His Absol Retic are up to 115,700, so he is regenerating, a definite improvement for us. Doc is adding Mycophenolate mofetil, another drug to suppress immune system, that she has had great success with, starting Monday or Tuesday.

@Sharon, you are so right....baby steps! And I'm hoping they continue, and turn into big leaps!

Mr. B is resting now, happy to be home. Thanks again for all your support!

Sally and Bentley
Sally Louisiana


way tooooo goooo Bentley, keep up the good work:)

Welcome home!!!!
Cheryl & Ginger
Cheryl & Ginger Pinevile PA


Yeeeaahh Bentley! Go Bentley Go!

Good news Sally, one step at a time.

Richard and Dylan
Richard Burnaby


Yay! What do think helped bentley regenerate the reticulocytes??

So happy for you!!
Christina New jersey


Christina,

Not really sure....it could have been that the Prednisone finally kicked in. Or maybe upping the dose of Cyclosporine to 25 mg 2x/day (done 4 days ago) did the trick. He was down to 75000, so almost making nothing. So a tiny step in the right direction....still a long way to go.

Any more news on Lola....thinking of you and saying prayers!

Sally and Bentley
Sally Louisiana


@Patrice,

I'm hoping you can shed a bit more light on the hypothyroidism theory....if this does occur, will it show in Thyroid tests, and if so, which ones?

Mr. B's latest CBC results are as follows (as of 7-15-11, pre-transfusion)
PCV 17
RBC 2.26
HGB 5.2
HCT 17.1
RDW 23.1
MCV 75.5
Platelets 224
Abs. Retic. 115.4
WBCs 29.1
NEU 23.0 (79.0%)
Bands 0.7 (2.5%)
LYM 1.6 (5.5%)
MON 3.8 (13.0%)

There were a few clumps in platelets, so a bit of a lower number, but still within normal range. Also were few spherocytes, so still some destruction going on. After transfusion last night, tho, his PCV went up to 35 and he is now regenerative. White count is going down, especially LYM, so I'm hoping these are positive signs.

Thanks again for all your help!

Sally and Mr. B
Sally Louisiana


Sally I am so happy you have your boy home. Hopefully you will see more and more positive signs.
Penny
Penny Lytle Creek Calif


Hi Sally,

I have Dr. Dodd's book "The Canine Hypothyroid Epidemic" written for dog guardians and veterinarians and they need to do a full thyroid panel. Tests included are for T4, free T4, T3, Free T3, TgAA (Thyroglobulin Autoantibodies), T4AA, T3AA (circulating thyroid antibodies), and TSH (Thyroid Stimulating Hormone). I don't know if all labs do it, but I know Dr. Dodds' lab does.

Also, the usual test is for T4 alone, but the Autoimmune form pf Hypothyroidism keeps levels of T4 normal so hypothyroidism is misdiagnosed in most dogs. The autoantibodies prevent the conversion of T4 to T3 the active form.

This is not well known yet, but it is well supported work and I have no doubt it is accurate.

Hope that helps,

Richard
Richard Burnaby


Thanks so much, RIchard!! That's what I needed to know!

Mr. B has eaten a great supper, had his meds, and is resting comfortably tonight :)

Sally and Bentley
Sally Louisiana


Guys, Help Please!

I have messed up again!! We came home from LSU yesterday with a few days worth Sucralfate for tummy, to give 3x day.....Somehow, I missed the part about not giving it with his Prednisone!! He's had two doses of these drugs at the same time....How much damage have I done????

OMGosh, this illness is a nightmare...I'm trying so hard to keep this pup alive, but I'm having such a hard time keeping this all straight....

Sally
Sally Louisiana


Sally:

No need to panic - trying to keep dosages and times straight at first is extremely difficult. You haven't done any damage. I can't remember why you need to give those two separately (it's been a while) but I think it has something to do with protecting the stomach/absorption. Also, the cyclosporine should be given on an empty stomach (that part I do remember). Many people here find it helpful to make a chart so they remember what drug to give when and whether it's with or without food. Hang in there - it does get easier as you get used to the routine.

Rita, Mike and (angel) Sheba
Rita IA


Hi Sally,

I think it prevents absorption of the antibiotics and maybe thyroid hormones (although I cannot find any specifics to support this statement). Likely all you can do is correct the problem in the future. I don't know about the cylcosporine or prednisone, but I don't see them listed as contraindications for sucralfate/carafate. I am sure Patrice will be here soon to let you know exactly what to do.

Yes, things are complicated, but you will get the hang of things. My experience was that there were several times where requirements changed drastically and they were tough and very stressful times. After a little practice they became easier and I also worked to make sure I had a system in my mind for feeding drugs. Something I could repeat and know where I was and what I was doing at any moment.

Exactly how and where the prednisone went and anything else was completely systemmatic. The pill bottles had the pills on top and until they were all gone and fed to Dylan, none of the pill bottles went away. They were in order and I had the same ritual each meal. Once I was done, I put everything away. Same thing every meal.

Again, it is difficult and it is hard, so try not to add stress to yourself if you can. Forgive yourself for being human and not a robot. I am sure from what you have written here that you will do fine and are doing fine. I am faily certain all you can do is give the sucralfate ahead of the others next time.

You ar edoing fine, I ams sure you can find a system that works for you. Maybe a menu, or list of instuctions to check off as you go.

Take care and try to take a moment to relax,

Richard
Richard Burnaby


Thanks guys....Just when I think I have it down, things change....I'm taking your advice and making a nice chart. I can handle the ones at mealtime fine, its the ones in between that have been giving me fits. The vet tech told me how to slurry the Sucralfate, but not to avoid mixing it with other meds (it can affect their absorption)....and I just failed to see it on the discharge papers....I HAVE to be sure to read EVERYTHING more than once, I've now learned!!!

On the plus side, Mr B looks happier than he has since his diagnosis...PCV yesterday was 35 thanks to the transfusion, so at least he feels better for now :)

You all are the best!

Sally and Bentley
Sally Louisiana


I think Bentley will be just fine and I think most of us have made a mistake on the dosage or timing of the pills at least once. I once gave Ginger's pill to one of my other Golden's and then the best one was a few weeks ago I opened Ginger's 25mg of cylcosprine and walked over to the fridge and grabbed a cup of water and took it myself...crazy but I was just not thinking and I was just fine and don't worry Ginger got her pill too.

Glad to hear Bently is doing better:)

Cheryl & Ginger
Cheryl & Ginger Pinevile PA


My big fear was always giving the prednisone to the wrong dog, espcially the real high doses in tghe beginning. My other dogs are all smaller than Dylan, so he dose would be immense (they would have been fine with a single dose, I know now). More than once I had the bowls in the wrong spot and filled the wrong bowl, but was fortunate I never did actually did mix them up (not that I know at least;-)

@Cheryl, I am looking for the "like" button on taking it yourself. I cannot count the times I have found myself stairing into space wondering what I was doing. In the wrong cupboard, or about to do something like feed myself the pill.

I think that is one big reason a system is necessary. Exhaustion and stress will understandably lead to mistakes, "accidents" in the true sense of the word.

So glad to hear you are continuing to see good things with Bentley. I know the high pcv is from the transfusion, but that is still a great thing.

Richard
Richard Burnaby


Hi,

In Dr. Dodds' book on The canine hypothyroid epidemic, she also suggests a journal to record anything necessary. Drugs, doses, behavior changes, symptoms severity and when they appear etc. These things may be of benefit later when you are trying to figure out what is going on then.

I have a pretty good memory for behavior, but dates are bad so I have tried to keep a few sources of record in order to associate what is going on in Dylan with when it happened. My videos and photos, this site, facebook and my own documents all record what has been going on in detail so I can look back if and when necessary. Even if it is just to remember; to me this is important too.

Go Bentley, Go Sally!

Richard
Richard Burnaby


Sally,

What had worked well for us was the pill dispenser that you get from the pharmacy that has a compartment for each day of the week - both AM and PM - and then the other "special" pill bottles on a tray next to it, like the sucralfate (to be given separately) and soloxine (on empty stomach). Most of the pills end up in the dispenser and you therefore only have to fill that once a week, preferably in a sane moment!

And then hopefully real soon you, like us, can celebrate not having to use the dispenser anymore! And then your only worry is what gets administered every other day and every third day. That's when the calendar on the refrigerator comes in!

So glad to hear all is going well!!!

Sharon
Sharon PA


Sally,
Nice to hear he is perking up, very good!

Test results:
PCV 17 moderately low
RBC 2.26 moderately low
HGB 5.2 moderately low
HCT 17.1 moderately low
RDW 23.1 Red blood cell distribution width: this is a measurement of red blood cells volume. It is used, along with other values like MCV to determine the cause of anemia. This value is relatively high indicating a wide range of red blood cell sizes. This means that some cells may be damaged, some normal, some very large (baby blood cells). It indicates a state of anemia. This is best combined with a visual inspection of a blood smear under a microscope.

MCV 75.5 Mean corpuscle volume: measures the size and volume each red blood cell and must be used in conjunction with other "M" values and the RDW to determine the type and possible cause of anemia. This number is on the high side of normal and may be considered normocytic (normal RBC) but could possibly be seen as mildly macrocytic (large RBC). Often it indicates the presence of a high number of reticulocytes. A high value could also indicate vitamin deficiencies like B12, a low value could indicate iron deficiency.

A dog with non-regenerative anemia will show normocytic (normal RBC) red blood cells. That is because the dog's body is not destroying red blood cells in circulation (and not making new ones). The cells in circulation were made prior to the beginning of the non-regenerative state. When a dog begins to make new red blood cells (reticulocytes)(regnerative anemia), they are larger because they contain RNA. A increased response by the bone marrow to create reticulocytes will cause the MCV to rise and this can be called macrocytic (large RBC) anemia. For comparison, microcytic (little RBC) anemia has several identified causes. The most common is iron deficiency and less common is a liver shunt.

Platelets 224 reduced numbers, but not in the dangerous zone

Abs. Retic. absolute reticylocytes. 115.4 (115,400) moderate regeneration (as combined with the PCV of 17), is dependent on the degree of anemia. This value is arrived at by using a mathematical formula that takes into account the severity of anemia. The lower the PCV/HCT, the greater this number must be to be considered regenerative. For instance if the PCV was 8 this might be need to be as high as 400,00-500,000 to be considered regenerative! This is all figured out either by hand with a mathematical formula or the current automated laser analyzers figure this out with sophisticated computer formulas. But the math is not that difficult so any vet should be able to figure this out. I did my own math with each test result.

WBCs 29.1 still high, but has dropped from 35.42, good
NEU 23.0 (79.0%) the most common white blood cells, value high, infections and stress
Bands 0.7 (2.5%) moderately high. this is large response by the immune system to produce new neutrophils (Called a left shift). Bands must be watched carefully from test to test
LYM 1.6 (5.5%) normal value
MON 3.8 (13.0%) high values possible causes: stress, autoimmune disease, infection and a response to prednisone

Platelets clump at the feather edge of a blood smear and is a common laboratory problem. However, techs are very used to this and can make accurate measure of the numbers visually. If they say they are in a normal range then that is accurate.

A rise to a PCV of 35 is good. It indicates that the blood volume (water plus the blood elements) has been brought back to a normal range. This is important to make the dog feel better. They may have administered electrolytes via a drip.

Keep the sucralfate away from meds and food, it interferes with absorption! I used it during the overnight fast for Chance. Think of this stuff as a "bandage" on the surfaces of the inside of the stomach. Don't worry you missed a few doses. Just start fresh at the next scheduled time.

Thyroid test. Call or email Hemopet for their recommended test.
http://www.hemopet.org/services.html

Here is the test submission form that the vet can enter information on line:
http://www.hemopet.org/files/TEST_REQUEST_FORMandTESTING_DETAILS.pdf

I suspect they will recommend Thyroid Panel 4 (T4, free T4, T3, free T3)
my best
patrcie
Patrice NYS


Thanks again, guys, for coming to the rescue! I have made a chart for Mr. B's meds, and set appropriate alarms on the IPhone, complete with the dog bark as the signal! LOL I'm going to go over it with the vets to be sure I have the best possible timing for all the meds involved. Cheryl, I was ROFL at you taking Ginger's meds....I can SO see myself doing that too!!!

And thank you too sooooo much for all the explanations....they help immensely. I'll say it again, this is quite the learning curve!

Mr. B had a great day yesterday....he was back to his old self! He turns circles when he wants a treat, or needs to go outside, and boy was he turning circles!! And his little tail was wagging like crazy! I'm just praying the meds start working and the numbers stay up....

We go back tomorrow for a recheck...I'll let ya know what we hear! Mr. B sends his love :)

Sally
Sally Louisiana


UPDATE:

Well, we just got back from our local vet (WOAH)....PCV was 33. I know those numbers aren't always exact, but it's a tiny drop from the 35 right after the transfusion last Friday. BOO!! Bentley's still acting better, and LSU internist has started him on Mycophenolate Mofetil (75 mg/mL), 1 mL 2x day.

We go for another full CBC at LSU Friday. Here's my question: How long do I give these meds to kick in?? One of the vets said we should see some response to a med within a week or so....If that's true, then he's not responding to either Prednisone or Cyclosporine....Have you guys found it to take longer than that?? I just don't know at what point I can be sure he isn't ever going to go into remission.

Thanks to everyone for their support!

Sally and Bentley

Sally Louisiana


Sally,

I think I heard that the drugs can take up to two to three weeks, but I'm not quite sure of that and I'm sure someone more knowledgeable can respond to that one.

BUT... want to reassure you that a PCV of 33 at this stage of the game is wonderful! Also, please keep in mind -- your main barometer for how Bentley is doing should be how Bentley is acting versus what the "magic number" is. Beau was at a PCV of 22 for quite a long time, but you'd never know it! His body acclimated to the lower oxygen level and he was just as playful and active as when he was "normal." So please try to focus so much on the number itself but on the behavior.

Sounds like great news to me though! Keep it up Bentley!

Sharon
Sharon PA


33 wow that is an awesome number, it took Ginger 6 weeks before she got out of the upper 20's. So I think you need to give the meds a little more time.

Tell Bently keep up the good work!!!
Cheryl & Ginger Pinvelle PA


I guess I'm worried less about the number itself, and more that it went down again. Although a friend on FB with an IMHA dog said she had two PCVs done in one day, and they were four points apart. I'm just so hoping for an upward swing, rather than this constant downward slide. How long before the numbers go up on their own, without a transfusion? Right now, we are at Day 18 after diagnosis.

We ARE enjoying him being much happier :) And holding out hope!

Sally
Sally Louisiana


Sally,

Remember those baby steps I told you about?!?!?

Right after the initial onset of IMHA and two transfusions (late-October), Beau's PCV steadily climbed to about 38. In late-December it began to drop. And then drop. And then drop. To the lower-20's. But he did great the entire time despite increasing liver failure from the prednisone. And a bladder infection.

When I started to see the internal med specialist at the end of January, he began to taper off on the prednisone and azathioprine (and add antiobiotics for the infection). Scared me beyond belief! But as the dosages decreased, the PCV steadily climbed. But it took until about April for the ascent to really begin. In May he reached a PCV of 29. I cried. In June it went into the high-thirties, and then 40. Cried again. Last week it was a 42. I was too shocked to cry because I didn't think I would ever see that day.

And now I only look at his gums about every 48-60 hours instead of every 45 minutes!

Moral of the story... patience! I know -- much easier said than done. But Bentley will get there!!!

Relax! And continue to enjoy him being much happier!

Sharon
Sharon PA


Hi Sally,

That is a great number and I would not read anything into the decrease at all just yet. Way too early for that.

One thing you have to try to remember, is that the numbers following a transfusion are complicated. They are not generated from the body, but if all is well, maybe they are a combination of the doner's and Bentley's. They are mostly received from the doner initially, then they begin to balance with the body, which in your case is a balancing a normal dog with an anemic dog so they will always go down initially. It just means Bentley has a more to do before he can be considered "normal." Sounds just fine given what he is fighting and where he is in that fight.

What I also know is; is that in some cases, several transfusions have been required before recovery is observed. Unfortunately, what you need to see is somthing that takes time for the body to do, that is first the immune system must be shut down and then also they need to make mature red blood cells (and the others too). You will see a decrease to some degree I think no matter what for now, as Bentley will still likely not be contributing enough to keep it at the initial, post transfusion level. Where it settles will matter and what they see in the blood ongoing will matter (reticulocytes, spherocytes etc).

The eveidence for the drugs working might be taken from other signs, maybe decereased breakdown if you saw spherocytes earlier. Or behavioral signs like water consumption, panting, peeing a lot when it comes to prednisone effect. Tell me what is going on in detail with his behavior. More energetic obviously, but what do you see around food, like your food (kibble does not count) - I saw a "snatch and grab" for any food I had that Dylan normally knew she had to resist and serious aggression as she reacted very strongly to prednisone. Do you see aggressive behavior at all?

Drugs can take longer to kick in too. Being sure may require more time and more tests. I have seen drugs inhibit recovery too, but I feel that that is NOT the case with Bentley. In those cases we saw a rise in the numbers without transfusions, then a fall.

Bentley needs more time for sure, and what else? Maybe Patrice, or Dr. Dodds might know. I really think he is doing very well for the current stage he is in. He is at the beginnning of building cells, hopefully. This only started recently, even if the drugs kicked in earlier this week.

Hugs,

Richard and Dylan
Richard Burnaby


Thanks, Sharon.....trying to remember the baby steps :) And really trying to relax, and enjoy Mr. B!
Sally Louisiana


It's normal for the crit to stabilize like this Xnumber of days after a transfusion. In most cases the crit will fall after a transfusion before stabilizing so in your case this little of a drop is very very good!!!

This drop is very small and shouldn't overly worry you. Is this just a PCV or did you get a full CBC? I always got full CBC's for Tessy that way i could follow the rbc, hgb, mcv, plt, etc. These are the numbers that'll tell the tale! Important to follow so one can fully understand how the body is responding to the meds.

Often times people will rely solely on the numbers but you really should use these combined with clincal response. You say Mr. B is much happier and feeling better so that alone says LOTS!!! Follow your heart and your gut.

If you wanna chat shoot me a message on FB. I'm not around much lately ...lots of life stuff on the go and any extra time is devoted to Tessy. LOL

Lots of thoughts, prayers and vibes for Mr. B ...and hugs for you!
Johnny & Tessy
Johnny


Sally,
I think a PCV of 33% is fine, it is really a measure of the whole blood minus the plasma (just the "red" stuff.) So it can be dependent on how well hydrated he is. A dog or human can live quite well, with moderation, at this PCV for life if need be, (if the underlying condition is not resolvable, such as kidney disease). I have a neighbor who routinely has a lower PCV. They give him Epogen shots occasionally (stimulate the kidneys) to get his value back up a little. I am not saying this is what is happening to Mr. B, just using it as an example.

At this point with Chance I was more interested in watching his reticulocyte values to make sure that he did not slip back into a non-regenerative state. At a PCV of 33 there should be a mild regenerative state. You won't see whopping large numbers of reticulocytes, but there should be more than 60,000 absolute (more than 1%) which is the value associated with absence of anemia. Chance eventually settled in at 38 and I knew he was at "his" number because the reticulocytes settled at that 60,000 value.

Dogs with bone marrow failure have a different recovery window. The damage is occurring in the marrow not to the circulating blood. Dr. Dodds uses the best word, intractable, or less responsive to the treatment. She has varying increased steps in her treatment protocol if this occurs so there is continued suppression of the cytotoxic killer t-cells.

With Chance I saw some small movements in reticulocyte values at 3 weeks and then a very gradual rise over the next month or so. In total it was probably about 2 months before I was completely sure he was truly out of the woods. Each dog is different. But certainly our goal from the very beginning was to get the prednisone decreased as soon as possible to relieve the very serious side effects. If you can do that now, then that is a very important step in giving the medicines time to work without making him overly ill from side effects.

Check out the first three photos of Chance to see how long the recovery to good health was. He looked awful at the end of summer, but his marrow was beginning to recover.
http://www.flickr.com/photos/patricel/2857651904/in/set-72157602714279765/
my best
patrice
Patrice NYS


Thanks guys, for the replies....

Bentley's numbers before the transfusion were PCV 17 and Absol. Retic. 115.7 After the transfusion last Friday, his PCV was up to 35...today it was 33.

So we'll see Friday what the full CBC shows. He is regenerating now, and that was a big improvement from the previous CBC on July 11....then, his Absol Retic was 75.0.

Patrice, is this what you mean? Seeing this improvement in the Absol Retic? Are we nearing the point where the vets may consider reducing Pred? Would the other meds be left in place? I guess first Bentley would have to hold this PCV, correct? So far he has not done that...after the first transfusion, he slid right back down to 17.

Yikes, this is a hard, long road! Thank goodness you guys are all here :)

Sally and Mr. B
Sally Louisiana


Patrice,

I looked at those pictures... I see what you mean about the road to recovery being long. Your Chance is certainly a handsome boy!!! And your little girl is a cutie too :)

Sally
Sally Louisiana


Sally,
You may have not seen the selective parts of Dr. Dodds protocol for bone marrow failure that I posted for Lola. This is pretty much what I used. You can see the drugs that she recommends, the dosages and durations. We never had to use aza, Chance responded to the cyclosporine (when he did not respond to prednisone) If a non-regenerative dog doesn't respond to cyclosporine, then the aza is added. This is what I am talking about. Watch the reticulocytes now. It is very desirable to begin reducing prednisone if at all possible. This is a decision to be made by the attending vet.
my best
patrice

IMMUNE-MEDIATED HEMATOLOGIC DISEASE AND BONE MARROW FAILURE
W. Jean Dodds, DVM HEMOPET

Immune-mediated hematologic disease is being reported with increasing frequency in animals and humans. In the dog this syndrome is often associated with bone marrow failure. .....nonregenerative or poorly regenerative erythroid response; severe thrombocytopenia; profound leukopenia; other autoimmune diseases especially thyroiditis; active erythrogenesis, granulocytopoiesis or megakaryocytopoiesis with maturation arrest at the early stem cell level; and poor response to standard treatment protocols with corticosteroids and other immunosuppressive drugs.

Our experiences with these cases indicate that:

1) Autoimmune thyroiditis/hypothyroidism is frequently present

2) Aggressive and more sustained treatment with corticosteroids is needed. Suggested doses are: Prednisone or prednisolone given at 2-3 mg/lb/day divided BID for 5-7 days, or dexamethasone equivalents at 0.25-0.35 mg/l b/day divided BID.

3) For severe cases, other immunosuppressive therapy is given. We prefer cyclosporine (Atopica, or Neoral, or Sandimmune, 100 mg/ml oral syrup) instead of cyclophosphamide (Cytoxan) and give it at 10 mg/kg for 5 days rest 2 days, then at 5mg/kg for another 5 days. The lower dose is repeated after a 2 day rest on a 5 days on, 2 days off cycle as long as is needed (usually 2-3 courses of 5 days). This drug induces rapid T-cell suppression within about 48 hours and has been safe, effective, and well-tolerated at these doses. In cases where sustained more potent immunosuppression is required for clinical stabilization, azathioprine (Imuran) should be instituted along with cyclosporine. Dose is 1 mg/lb/day for 7-10 days initially followed by a downward tapering over several weeks. Azathioprine may be needed every other day or less often, on a longterm basis. As azathioprine takes about 10 days to effectively suppress T-cells, clinical responsiveness will not occur immediately. Cyclosporine is therefore given concurrently in the early stages of the disease to provide rapid immunosuppression until the azathioprine takes hold.
The goal of this immunosuppressive therapy is to stabilize the ongoing immune destructive process. The dosage guideline we use is adjusted to maintain the absolute lymphocyte count as about 1/3 of the normal range (750-1500/ul).

6) Hematinics containing iron, vitamin B12 and folic acid [e.g. Pet-Tinic] are helpful to provide the nutrients needed for hematopoiesis.

7) In poorly responsive immune thrombocytopenias (ITP), an initial dose of vincristine (Oncovin, 0.01 mg/lb IV) may be helpful to release remaining platelet stores, and danazol (Danacrine, 2.5-5 mg/lb BID initially and then tapered to SID) has been effective along with steroids and thyroid for longterm maintenance.

9) Cases with the best overall prognosis tend to be younger animals in which the underlying primary "trigger" of the immune-mediated disease was hypothyroidism, a drug which is withdrawn, or a recent vaccination/toxic exposure. Correction of the thyroid disease with serial monitoring of thyroid function to establish the appropriate maintenance dose of hormonal supplement is important.
Patrice NYS


It seems a little too early to be considering a prednisone reduction IMO. Several factors will help them in considering this move.... current suppression counts, spherocytes seen?, chemistry results (hepatic and renal function), adverse effects, etc. The general rule of thumb is to wait for a stable count of two weeks or more.
One med at a time with reductions when the time comes.

Johnny & Tessy
Johnny


This is a decision to be made by the attending vet.
Patrice NYS


man i wish i could add some helpful input like everyone else, but all we can do at this point is send our thoughts and love! i've been singing and dancing for lola. my friends think i'm crazy, and lola seems to as well..but i feel like its more positive then the usual crying that i do!! lola loves her legs scratched too!! its calms her and makes her sleep! best of luck sally. i think our pups are going to get better. <3
christina new jersey


Hi Sally!
I'm afraid I don't have any other advice to give. There is so much good stuff here and so much to ponder as you move forward with Bentley. I too think 33 is a "good" number. William held at 28-29 for a loooooong time and was active, happy and alert. We just got to a new average for him.

So, here's my 2 cents; hug up Bentley, try not to fixate on numbers and what you are or aren't doing at every second and, did I mention hug up that pooch?

Give Bentley a big lovey squeeze for me too!! (but not too hard since he's a little guy)

Liz

Liz Ohio


Sally,

When you're done hugging up on Bentley as Liz suggested, here's a suggestion from me...

Start a new thread called "My Pup Bentley is Getting Better!" For two reasons: (1) this one is getting rather long! and (2) it will keep you looking ahead!

Sharon
Sharon PA


This thread was discussed between 08/07/2011 and 20/07/2011

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