Canine Autoimmune Hemolytic Anemia (AIHA & IMHA) - PRCA and Reticulocytes

Hi

I'm out of my depth with this illness and all I seemingly encounter is negativity from vets - as if I don't already know this situation is life-threating.

Yesterday Shaunna's reticulocyte count was 0.4 and today it was the same so she is still classed as non-regenerative. However, prior to this it was 0.0.

Does it mean anything that this reticulocyte count has increased to 0.4. Yesterday the vet said it was encouraging, but because the figure has stayed the same today, it doesn't seem to be classed as positive. I think the ret. count should be between 0.5 - 15 so Shaunna isn't classed as regenerating - but does this small climb mean nothing then?

Claire

Claire Cumbria

Claire,
In a normal human or dog, the number of reticulocytes in circulation is about about 60,000 and between 1-1.5%.

In a dog with anemia, non regenerative is classified as being >60,000 (less than) or below 1%. For example, when Chance was first tested his reticulocyte count was 36,000 and his PCV was at 30%. So thus, his PCV did not fall within the normal range of 38-45 (to 55 in some breeds) and would be considered anemia.

To be considered regenerative, the absolute number needs to be higher than 60,000 and it needs to be much higher than that in a dog that has a very low PCV (say below 20) to be considered even moderately regenerative. So if a dog had a PCV of 15% and was regenerative, the absolute number of reticulocytes could be very high, as high as 500,000 and 4-5%. Do you understand this? The lower the PCV, the more reticulocytes there must be to be considered regenerative. There is a specific mathematical formula that is used to determine this scale.

Make no mistake, a non regenerative state is very ominous. This indicates a failure of the bone marrow for some reason. What is that reason? Dr. Dodds explained this to me carefully. There can be a number of causes, like bone marrow cancer, but in some unlucky dogs, the damage by the immune system happens to the precursor cells in the bone marrow. These cells are like blanks and they are made into red blood cells, white blood cells and platelets. (Think about all the hullabaloo about stem cell research, these cells are similar). So they start to form new red blood cells but fail to finish. Chance also had no white blood cells either, so his case was doubly ominous. If a dog also fails to make platelets, it is indeed an extremely dangerous scenario. This is called pancytopenia and means complete loss (pan around 360 degrees) of cells (cyto) (penia = little)

If there is no more hemolysis (destruction of red blood cells) then the number of red blood cells in circulation should gradually rise as these reticulocytes drop their RNA and mature into red blood cells. As reticulocytes they are very poor at carry O2 and are a bit larger than a RBC. This process can take about 2 days to a week.

If there is hemolysis still occurring, then there is still destruction of red blood cells, the body could remain in a highly regenerative state, pushing out reticulocytes, but losing them to lysis. You would see high absolute numbers of reticulocytes, but the number of red blood cells would not rise. This would be an ominous sign.

So at some point, the number of reticulocytes should diminish in the blood stream and hover around 60,000 and 1-1.5%. The number of RBC should at this point have risen to somewhere around 5.5 million. This would indicate stability. The PCV would ideally read around 45%.

I like to use this explanation to help people understand. Imagine you have a glass and you want to fill it with water. You walk to the tap, turn in on and begin to fill it with water. If fills, you slowly turn off the tap and the glass sits there, full to the top. With evaporation, you may have to add a teaspoon or so of water to keep it full, but not much. This is similar to the normal replacement of old worn out red blood cells (at around 120 days) they don't all age at the same time.

Now imagine that glass has a hole in the bottom. You fill it up but for some reason, as you fill the level keeps dropping. You turn the tap higher, but it just won't keep the level up to the top. This is similar to hemolysis or loss of red blood cells. Eventually you can't keep up and the glass will be empty and the water will just flow from the tap through the hole.

If you repair the hole in the bottom, the glass should refill and eventually be full again. You can now turn the tap off. So once hemolysis has stopped, the body should eventually reach a steady state or homeostasis and that would be indicated by around 60,000 reticulocytes and 1-1.5% in circulation. In dogs that have recently gone through hemolysis, these numbers might fluctuate up and down a bit, but it is not worrisome.

If the number your vet said went from .0 to .4, that really means it went from 0,000 to 4,000. That means you still are below 60,000. Is this a sign that there is regeneration occurring? Chance started out very slowly also, and it took probably around 2-4 weeks for there to be any significant rise. But the vet and I still did a happy dance when we saw that first change. Eventually he was up around 450,000 reticulocytes.

Is this as clear as mud? Please ask me any questions you have about my explanation.
my best
patrice

Patrice NYS

Note to self, proof read copy.
">60,000 (less than)" NO, this is <60,000 (less than).

Also, check with your vet for their particular automated analyzer scale. .4 could indicate 40,000 not 4,000. And ask if this is absolute numbers.
patrice

Patrice NYS

Patrice

I was told yesterday Nollaig's retic count was 0.12 x 10^6 which is 120,000 and her pcv 21.9% and they classed her as mildly regenerative. Before she was classed as poorly regenerative so they saw this as a slight positive change yesterday.Nollaig has been on treatment for pure red cell aplasia now for 6 months.

However I don't understand how her regeneration is better than before if she's still dropping pcv at the same rate as before if not slightly higher rate? Nollaig's specialist internal medicine vet believes her precursor cells are being attacked, but there is no attack going on in the circulation so no hemolysis.So why when she goes from poorly to mildly regenerative is her pcv dropping at just same rate or higher than when she was poorly regenerative? I don't get it!!!

Please enlighten me.

Kathleen and Nollaig

Kathleen North Ayrshire

Patrice

Many, many thanks for the explanation - after reading through it twice, it made sense and i think I've now grasped it.

So in essence then, Shaunna still isn't classed as regenerative...

SO, after being on treatment for 2 weeks should I see this reticulocyte increase to .4 as positive?

Should I expect the count continue to rise or could it fall again or stay the same? I guess this is a stupid question.

Claire

Claire Cumbria

Claire,

One very good piece of advice I got in connection with this disease was: It is not a sprint, it is a marathon. I am certainly not an expert, but all the increases seem to happen very slowly. I have learned to be very patient. Sometimes the wording vets use sounds so very negative even if it is not intended to be. I am not suggesting Shaunna's disease is not very serious. The retics not increasing is clearly very serious. However the numbers are not going down but a tiny bit up, so that is positive! don't be discouraged, it will improve.

Best wishes,

Brigitte & Kahlu

Brigitte BC Canada

Hi Claire,

Good to hear from you but sorry to hear you feeling so down and bewildered.

I personally have not been bamboozled with the figures etc for reticulytes but after the bone marrow aspirate I was told that Mitch had ITP and was killing the platelets early in the development in the bone marrow. At this point which is 8 days ago they said he was producing red blood cells because there was evidence of reticulcytes. The biopsy results from this bone marrow took longer to get back and on Tuesday evening I was told he was also AIHA and was non-regenerative. If you read the 'Kath and Mitch' post you will see my despair at this point. 24hrs after that I get a phone call to say his PCV and platelets are increasing and that he may even come home this weekend. What I am trying to say is that it may take time and more so with PRCA because she will have to start right from the very beginning of making RBC and getting them into the blood stream. It's not just about stopping killing them in the circulating blood itself.

I know how infuriating it is - I believed I would see an improvement in Mitch after 4 days on prednisolone and yet after 8 days absolutely nothing. At this point Cyclosporine was also given and after another 5 days at last a response is seen. It has been two weeks of medication before any improvement shown.

This is a rocky road and I know how low you must be feeling and every day I asked the vets - shouldn't we have seen an improvement yet- and the answer was it takes time. Please hang on in there and be positive for Shaunna, I am thinking of you and Shaunna and know exactly where you are at right now. Just because you can't see anything yet great things may be happening underneath the surface.

Please stay positive, sending you big virtual hugs.

Kath Fife

My good buddy Chance was on high dose (80mg daily) prednisone treatment for nearly 2 months with no change before cyclosporine was added at 225mg daily for 8 more weeks. So it was 4 months of non regenerative anemia before he responded well on the the Atopica. He survived on transfusions.

He also was not making white blood cells that whole time. So he was on constant antibiotics. I had to monitor his body temperature multiple times a day in case he developed a severe infection. He was diagnosed at a PCV of 30 and eventually dropped to 18. I let it go no lower than that before transfusions because clinically he was a mess.

No, Shauna must get over 60,000 and, depending on her PCV, rise to numbers like 400,000 to be classified as highly regenerative. If there are some reticulocytes being produced, there are several reasons why there are not more. 1. they are being destroyed by the immune system in situ as they are manufactured. 2. the body is having a hard time making them because of some condition like low thyroid or nutritional deficiencies 3. there is smoldering kidney disease and there is not enough erythropoietin being manufactured to jump start the process 4. there is a maturation problem, they mature but are not healthy, but stay small and are unable to carry significant hemoglobin (because of low iron). I know *now* very well that this can indicate A SEVERE LIVER SHUNT. It can also indicate a severe nutritional disease of the gastrointestinal system. 5. there is aplastic anemia caused exposure to toxins (like Benzene), certain drugs, radiation or viral hepatitis (liver disease). 6. There could be leukemia of the bone marrow.

Needless to say, this is a huge laundry list of diagnosis. And any vet would feel somewhat overwhelmed by this. But talking with Dr. Dodds calmed me down some. I was able to get past worrying about all those other crazy causes and focus on the fact that, in her experience, there are more dogs being diagnosed with autoimmune non regenerative anemia (at the cell precursor level) than ever before. In other words, a simple matter of suppressing the correct rogue elements in the immune system strongly enough to be effective. That's the killer t-cell lymphocytes. And knowing Chance's history of severe allergies, it made complete sense to me that this was what was really happening.
patrice

Patrice NYS

This thread was discussed between 13/08/2009 and 14/08/2009

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