Good evening everybody and welcome to tonight's webinar. My name is Bruce Stevenson and I have the privilege of chairing tonight's webinar. I think we have quite a few new people on tonight, so just a little bit of housekeeping for those of you that don't know.

If you have got any questions for our presenter, he has very kindly agreed to stay afterwards and answer. So all you need to do is hover your mouse over the screen. The, black control bar will pop up, click on the Q&A box, type your questions in there.

They will come through to me and we will hold them over until the end. And then we will cover as many as we possibly can. So tonight, you're in for a treat.

I've seen Craig's presentation already, and it looks fabulous. Craig Bretney graduated from the Royal Dick School of Veterinary Studies, followed by several years in a busy first opinion practise in the Northeast. Craig returned to complete an internal medicine residency and a dip and he's now a diploma of internal medicine.

He's currently a lecturer in emergency and critical care medicine at Dick Wits with an interest in acute medicine and teaching undergraduate students the approach to emergency cases. Craig, welcome to the webinar vet and it's over to you. Thank you very much, Bruce, and thank you everyone for coming along, giving up your time.

Hope you've all got some kind of gin or wine in hand, and then we can get started. So the plan is really to talk a bit about the approach to anaemia from when a case first arrives at the hospital or clinic wherever you are, and then how we go along to get that diagnosis of being an immune mediated condition and then just a little bit about how we actually go about treating these cases. So the reason I chose to talk about the IMHA cases today is because they're one of the most common cases that we'll see in both first opinion and referral practise.

And despite seeing them fairly often, they still have a high mortality rate, and depending where you read, it can be anywhere of up to 50 to 75%. And a big reason for that tends to be that these cases tend to be very thrombotic, so they can also often form blood clots very easily, meaning they can spread to lungs and the brain. So they can also be these cases that can be doing very well and suddenly deteriorate.

So they can be quite, you know, surprising cases from that point of view. And if we are going to see mortality, it's usually in the first couple of weeks after diagnosis. So that's really when we want to be getting in there, making hopefully an early diagnosis, and then managing them appropriately to try and minimise that risk.

So the first thing really, when we get presented with an anaemic patient, it's trying to work out what the overall kind of broad category that's causing that anaemia is. And for me it really falls into three categories. You've either got the regeneratives, which we'll touch on a bit more later on, non-regenerative anemias, or the pre-regeneratives.

And the pregeneratives, these are these anemias that will present as looking like non-regenerative. Actually, there's just not been that 3 to 5 days of stimulation for them to show that they actually have a regenerative underlying cause. And we'll see that typically the MHA is about 1/3 of those will present as being non-regenerative in the early process of the disease there.

And so when we're looking at splitting it, as I say, the preregeneratives really feed into the regeneratives, which we have further subdivide them into three broad categories. We have blood loss. Hemolysis, be it immune-mediated or non-immune, and another one again we'll touch on later on is a condition called hemohagocytic syndrome, that's pretty rare but still can catch a site occasionally.

And then we've got the nongenitives that we won't really mention much this evening, but looking at more, is a problem with decreased production, be it because we've got bone marrow outcrowding. We're not getting the messengers through, so things like a deficiency in earthroin or thyroid hormones, or is actually more of destruction again, but this time looking more at the bone marrow precursors. And trying to differentiate the regeneratives and non-regeneratives can sometimes be a little bit tricky.

So typically we'll go based upon the onset of clinical signs. So these dogs or cats that are, you know, they've been ill for 24, 48 hours when the owners are first appreciated signs, or are the ones that actually, you know, there's not been right for a couple of months now, and when they present to us, it's just been the straw that's broken the camel's back, and now they're just having that extra difficulty. Again, it's how well they tolerate anaemia.

So I imagine you're probably similar. We've all seen sort of dogs and cats come with PCVs of, you know, 8, 10% and the dog's wagging its tail or the cat's trying to have a go at you. And actually, those are the ones we think, you know, surely they should have a higher PCV to be as bright as they are.

That probably just tells us that although it's probably just been going on longer and so it's been adequate time to compensate. And in dogs, they just usually become more efficient with how they handle the oxygen and how well the haemoglobin binds and releases it. And then it comes to the sort of slightly more objective methods of looking at it, so we can use our haematology analyzers to help us.

And the classic values that we're looking at in this would be in particular are mean cell volume, telling us how big or small the cells are. And our mean cell haemoglobin concentration to tell us how much hemoglobin's actually packed into those red cells. And based upon that, they can help narrow the field about some of the differentials.

So because when the machine's doing it, we're getting an average, if we see a macrocytic and hypochromic anaemia, that tells us that the cells are bigger and paler, meaning it's probably a surrogate that we have more polychromatophys or reticular cytes in their circulation. So that can be suggestive of regenerative process. If we're seeing it as being more of a normaytic normochromic, then it's probably more like we've got non-regenerative and the cells are just dying off at their natural age, they're just not being replaced, or there's not been time for them to be replaced if we've got something like an acute blood loss, it's just not been time for.

And then we have some others that kind of tip us off in a different direction. So if the cells are small, particularly if they're hypochromic, we might look at more, do we have a potential iron deficiency from chronic GI bleeds, something like that, or could it be a dog with a shunt and actually anaemia is maybe less of a concern in these cases. And another thing we often do in hospitals, although we trust our haematology analyzer, it can have errors and different things can interfere with it if there's homolysis or leukaemia, so often we'll have a look at a blood smear ourselves and actually don't need much blood for it and relatively inexpensive.

And we'll come back onto slide later on, but just looking at this sm, you can see that this is really the picture of regeneration. So we've got quite a lot of anisocytosis, a lot of the cells are different sizes here. We've got a polychromasia with different colours, which just tells us that we've probably got a lot of differently aged cells out in the circulation.

And a big part of that's going to be things like the reticulocytes or polychromatophils that are just being thrown out before they're ready to actually become needed in these states of anaemia. And really if we're looking at it in terms of what's our gold standard and what's the one that tells us most definitively whether we've got regeneration or not, we're gonna be looking at the reticular site count. Now, typically the machine analyzers will sometimes give us a percentage of reticular sites, which is a much less useful method actually of having a look at it.

So what we have to do is convert that into something a bit more useful. So what we can do is take our particular site count percentage, we multiply it by our red blood cell count, so it's total and absolute number, and then we multiply that by 10. So if we've got an example here, we're looking at taking our reticulocyte count in this case, which is about 24%.

We multiply that by the 1.27%, which is our absolute red blood cell count and then multiply that by 10. And like kind of ornament, we get our numbers here and so we're left with a value of 307, so that'd be very regenerative.

And what that lets us to do is it tries to help us estimate the degree of regeneration we've got. So some things we'll have a bit of regeneration, but actually it's still inappropriate for the degree of anaemia that's going on. So we tend to say that in using dogs and cats, as long as it's ideally for it to be regenerative, we want to see a number above about 95, mild regeneration will be up to the 150, moderate up to 300, and we're seeing quite marked regeneration when the count reaches above 300, such in the case previously.

And naturally we want to be seen, we want to be seeing the bones actually trying to do something about it in these cases. So to focus on the regenerative anemias, which are gonna be the most important ones. And when we look at it, the three big causes are either we have blood loss, we have hemolysis for one reason or another, or we'll see something such as a hemohagocytic syndrome that we'll talk about it more in the next slide.

So there's one I don't think we see terribly often, but it's just worth mentioning cos it's one of these few ones that if we do see it, it can present a little bit oddly and mean that we don't always catch them as early as we should do. So it's one of these forms of cancer that originates from the histiocytes or looking at our macrophages, and we'll see different types, but what they give rise to is this hemaphhagocytic syndrome, where these cancerous macrophages start to ingest and destroy the red blood cells. And in these cases, they can present very regenerative, typically they look a little bit like a blood loss anaemia, so we will often see a little protein with it without finding an obvious source of the blood loss.

The thing that tips these off is usually we're looking for, well, where are these cancer cells and location. The most common one would be the spleen or the liver. We've got a good number of these, and actually, that's what they would normally do.

They're functioning normally, but this malignant transformation makes them a bit more aggressive. We can see also in in lungs, the bone marrow and the lymph nodes. So just worth bearing in mind.

And typically these cases, you know, we'd usually find them on imaging or have a strong suspicion based on other things, you know, based on what we've ruled out. So we try and get an aspirate, if that's not possible, sometimes a biopsy to give us an answer. And then because we can get different forms of it, you want it to be sort of, you know, very particular and be 100% sure on these cases, we can also have a look at different markers on them to try and work out what type they are.

But it's, you know, quite rare we get that far down the line, usually we get enough to say it looks like a cancerous process and unfortunately don't tend to off. Prognosis, a lot of owners will end up calling time there. But I think if you're seeing one of the classic breeds, which for us would be the Bernese Mountain dog, we'll see in Rottweilers, golden retrievers, or the flat coated retrievers.

They're the big ones that we maybe have this just a bit in the back of our minds, although they're relatively uncommon. So then again, the next thing we want to rule out, and we'll see relatively commonly is blood loss. And one of the easiest ways we can do that in sort of least expensive ways is to have a look at our pack cell volumes, our PCV and our total solids.

So a PCV can just be run on the, you know, centrifuge in the blood, relatively straightforward, have results pretty quickly. The total solids, I'm not sure how many people are doing that in practise. It wasn't something I did in practise before I came back to the uni here.

But actually it's sort of one of these things that's really easy. So we'll take our refractometer, we'll take our spun down hematocrit tube, and all we do is break the tube carefully at the point where the blood meets the plasma on the top, and then we just put our plasma onto the refractometer, flip the lid over and have a look at it. And usually we're looking at the scale that has our grammes per deciliter.

And then for convention, we convert it into grammes per litre. So we typically say a normal PCV for a dog would be anywhere from 30 to 55%, and our total solids, so our surrogate marker for our proteins, which correlate pretty well amongst each other, would be about 60 to 80 grammes per litre, or that would be the equivalent to 68 grammes per deliter, however, whichever unit you want to work from. And the nice thing for this is it's really inexpensive, quite quickly available, but actually we would expect if you're losing blood, then actually quite often your protein level becomes a more reliable marker, particularly acute blood loss, because we lose our whole blood, so we're losing the red cells and the protein at the same rate.

What will intend to happen is adrenaline gets sent off from a sympathetic nervous system with cortisol from your adrenals. And those act to encourage a splenic contraction. So quite often what we'll see tickling things like the RTA patients, our PCV will often be buffered for a period of time, whereas we don't get the same thing with the total solids, they'll continue to drop.

So if we get a dog presenting to us, it's very anaemic, and we check the total solids and they're low, then I'm gonna have either the hemohagocytic probably quite low down on the list, but I'll probably have bleeding higher up on the list. Whereas if we're looking at something like a hemolytic condition. That actually we're saying, well, it should only be the red cells that are being destroyed and the protein should be relatively unaffected.

So in those cases, we should find a total solid should be within normal limits there. So that's quite a useful thing to do. We've then got another thing that's really easy to do is a point of care ultrasound.

So these are really, we're not, you know, the base on the scanner we've got tonight, so it's not the fanciest one, but all we're really trying to look for is, is it a big cavitary bleed there at all. So typically we'll scan the chest cavity, we'll scan the abdominal cavity as well and see if there's any accumulations of fluid there. And if there is, and we think our clotting times and our platelets are looking OK, we might try and sample that just to ensure that it definitely is blood and not a bit of a red herring there.

Typically, you know, we can sometimes, and people we want a bit more about things like occult bleeding and after traumas and things like pelvic fractures and things. I think we just don't see it quite as often in dogs and cats, but we could have them on the radar. Apart from that, we don't really see cavities in the dogs or cats that are big enough that we could have a high volume of bleeding without causing other signs first, you know, if we've got bleeding into the.

Skull or if you've got bleeding into joints, and usually it'll become symptomatic and actually, or in the heart, you know, the pericardium usually tampona before the anaemia becomes the presenting problem. You'll see them for another reason first of all. So typically you know we'd be looking at a case like this where you see that nice triangle round about the GI tract or typically rounded by the liver or the bladders where we'd look in the abdomen for free fluid.

We then often have a look at a urine analysis just to see, you know, it's quite rare to lose enough blood through your kidneys, to become anaemic, but definitely can be done. Some of these idiopathic venal hematuria cases can really lose a good amount of blood. Some become iron deficient because of that, so it can become quite markedly anaemic.

What we really want to know is if we're getting a sample like this one on the right hand side, quite often what we'll do is spin that down to try and evaluate. If we get a nice little plug at the bottom, then we know it's a true hematuria. If it stays much like it is at the moment after spinning down, then it's more likely a pigment, be it haemoglobin or myoglobin.

So again, that might push us down a different route, so something quite cheap and easy to do. And then the other area and probably actually the most common one we'll see blood loss, it's not initially apparent, is from gastrointestinal blood loss. And typically one of the reasons it can be a bit of an issue is we'll get dogs and cats presenting that are maybe hypovolemic or because they are so anaemic.

They're in a state of shock. So in order to preserve blood supply to the brain, the kidneys, the heart, the blood supply to other organs such as the gastrointestinal tracts, pancreas, these areas become diverted, which means they'll often develop avius. So that can really slow down the normal gut transit time.

So it can actually take a bit longer before we'll find this melina that once would have been there, you know, if the guts were ticking along normally. So quite often we'll directly examine these ones when they present, just to see if we've got an obvious melina. Maybe the owners haven't found a pattern.

If it's still not sort of worked its way that far down, the other things we can look at to give us an indicator that we might have GI blood loss. Typically, if you've got it grumbling along chronically, there'll be a bit bone marrow stimulation. And so sometimes what we'll see is our automated platelet count will increase.

So we can usually end up with a thrombocytosis and a high platelet count, can be an indicator. The other one we often look at our biochemistry is our UL levels. So in these cases, what tends to happen is you're losing the protein into the guts, particularly if it's from the stomach or the duodenum.

It moves down the GI tract and gets digested just as it would if it's a high protein meal, meaning all that nitrogen gets converted into ammonia into urea, which then builds up in the bloodstream. So if we get a dog that's got a normal creatinine and a high urea, and we don't think they're terribly dehydrated or got high platelet count, then again, the index of suspicion for a GI blood loss becomes a wee bit higher on our list there. And again, probably relatively rare to see, but in particularly in smaller patients, when you're looking at puppies or kittens with anaemia, you might just want to look for parasitic disease as well.

So particularly what's their worming history like and have they been flea treated? Cause again, or you know, really heavy tick burdens in appropriate areas could also result in this. So typically once we've done those things, we'd say, right, if we're not finding much there, we've got normal total solids on our bloods.

We might then go down the route of looking for hemolytic diseases. And then again, because we're medics, we like to split things to as many categories as possible to make it as confusing to remember as possible. But what we typically get to is a point where we said, right, we've got some form of hemolytic condition.

Is it immune mediated or non-immune mediated? And that's the one we'll just go through a few examples of, just to bear in mind. So, because the red cells, the way they are, they're very reliant upon the phosphate and the serum in order to make sure they can get enough into the cells to form ATP.

If you become hypophosphatemic and there's actually not enough phosphate, then we've got enough ATP and without that, the red cells can't effectively use their pumps and the channels, meaning that they start to accumulate fluid and start to rupture. So we can end up with a hemolysis that's not immune mediated in those cases. And the classic examples would be the ketoacidotic dogs after we started them on treatment.

If we see the hyperparathyroids occasionally can go that low, or if we're using, you know, binders for chronic kidney disease excessively, potentially, or if we get these dogs like the one in the bottom there, it's maybe not eaten or being trapped in a garage, whatever it may be for a good week or so, and we suddenly feed them, that massive insulin release can also push the phosphate intracellularly, which causes us to run into trouble there. And I think it's pretty rare to get it low enough to cause these problems, which is something to bear in mind if you're finding that on your blood work alongside an anaemia. The zinc toxicity is one we do sort of lying on about quite a bit and it's just because it's a case that we treat differently.

So in the states, the big one people talk about is the Linc and Penny shown there after the year 1983, if you're looking at pennies enough, because what they can happen is, I know they've got the outer coating there, then say actually zinc based and they also see it with things like radiator keys. So if the dogs ingest them, they'll sit in the stomach for a bit of time, and the acidity in there can destroy them, starts to leach the zinc, they'll absorb it, and it can cause oxidative damage to the red cells, which means we can get an intravascular hemolysis. So we don't see it very often, but when we do, you know, they can be really severe cases, and we'll come on to how we screen for those later on.

And then a few more of this sort of weird and wonderful ones. So one of the ones that we don't see very often, but I just have on the radar is the phospho fructokinase deficiency. So it's a type of glycogen storage disease caused by a single mutation.

And the interesting thing about this is it just means that our red cells become more fragile in a more alkaline pH. So typically these dogs, the classic example here is one of the vets in the hospital he was treating dogs that wasn't a rehoming centre, and whenever the dog got very excited, we'd be up at the front seeing people wanting a house, jumping up and barking and panting get self excited. I mean, it was blowing off its carbon dioxide, so it became more alkalotic.

And as it did so, it just meant that red cells start to rupture. It then looked like it developed hematuria, so it would go away from rehoming until they got under control, would resolve when, when, when it went back out for rehoming, the same would happen again. And so these cases, because I sometimes see with quite severe anemias, and sometimes just inflammation caused by the red cell rupture can also cause pyrexia.

So one to have on the list, but things like whippets and the springer spaniels are kind of the classic breeds supposed to be predisposed. Oops, I think the theenji's covering the wording there, but what we can also see another type is a phospho sort of pyrobi kinase deficiency, and it's usually a recessive one. And again, what involves an error in metabolism in the red cells, they tend to have a shorter half-life and it'll rupture a lot easier.

And the problem these dogs have is. Rather than having a stimulus like the phosphoritokinase, they're just continually rupturing the red cells, meaning that there's this constant destruction, so they tend to be very regenerative anemias when you find them. The problem can be is because you're constantly.

Lies in your red cells and trying to take in more iron, they can become iron overloaded, so they can develop a condition called hemochromatosis, and the big areas that tend to suffer from that tend to be the liver, or actually just pushing all that iron into the bone marrow can also cause dysfunction there. So these dogs typically have a shortened life span, looking at about 1 to 4 years. And the Basenji was the one that was seen first in, but also Labradors, Dashing, Westies, can terriers, they've all been reported.

And if you're strongly suspicious, it'd be more genetic testing that quite a lot of few of the UK labs will run. And the other one we can see are these Hein's bodies anemias, these are the ones that, you know, we always see in textbooks about these little noses on the end of the cells, and if we stayed them up with the new methyl blue, they just show up as a bright blue colour to make them a little bit more obvious. And all that's happening is we've got something causing oxitative damage to the red blood cells.

They're now recognised as being abnormal, so they'll get taken out of the circulation by the immune system. And the classic one that most owners will be aware of will be the onions and garlic for dogs that have eaten those. Again, some things like particularly more so in cats, but things like paracetamol or if people are using, you know, long term propofol, CRIs, sometimes if they've got preservatives in them, they can also cause these conditions.

So just something worth bearing in mind. And then again, the thing that we touched on earlier. So once we've taken those out, we're then left with the actual point of the talk 20 minutes in, which is the immune mediated causes.

So these are caused by a type 2 hypersensitivity reaction, meaning it's antibody mediated, and it's all happening because something's causing, you know, like we're all aware that we should have our T cells, should recognise what our self antigens are, and know that they're not anything to cause a problem, we shouldn't be reacting against them. We lose these regulatory mechanisms, meaning that these cells then start to target the body's own antigens. And they can produce either IgG or IGM, so the IGMs tend to be the bigger 5 antibodies stuck together, so they'll sometimes cause more glutination, which sounds a bit more theoretical.

And depending on where they're acting, they can either label the cells as now being defunct or abnormal, which means that the macrophages and the spleen or the liver will then take them out of circulation and destroy them, equally, if compliment and things get involved, we can actually destroy them inside the circulation and that can just. Very slightly change how they present, whether it's more of a bilirubin overload or a haemoglobin overload and potentially intravasculars might have a slightly worse prognosis in these cases. So we're looking at breeds predisposed in the UK this a poster child for it is usually the cocker spaniel see it quite frequently and again we'll see another spaniel breeds as well.

So springer spaniels, also bearded gullies, Labradors, and the state side it's usually more presenting with things like the lumber spaniel potentially or in Australia. They'll also see it with things like the Maltese terriers. So there's a bit of breed variation.

So the big question is how do we try and get a diagnosis of these cases? And the top three there so insulin and glutination, the blood smear evaluation, and the Coombs test are the 3 big ones that we look at. And really what we want to try and get as a positive and 2 out of the 3 to be relatively convinced that we're going down the right lines with these cases.

So when they're in saline and glutination testing, my understanding was always sort of a bit of a misunderstanding, and I always thought the saline was really crucial for actually obtaining the diagnosis. Really, the point of the saline is to get rid of what we've got on the left here. So you can see that we've got those stacks of, or the coin stacks or the roule.

So this is when you've usually got something like a bit of globulin or higher protein content in the bloods or fat content, particularly in horses or cats, but we'll see in dogs as well. And they just change the electrical chemical charge on top of the red cells, meaning it's more favourable for them to stack up like a row of coins. If we compare that to the true luation that we've got on the right hand side here, you can see that rather than forming proper lines up, they're more like bunches of grapes, you know, forming complete clusters rather than these nice lineups.

So what we're doing when we're using our saline and dropping it into set of blood that's been EDTA treated previously, we're trying to disrupt that electrochemical signalling between the red cells, free them up so that we're not misinterpreting the root as being auto agglutination there. So you can do is really one part of ETTA blood to one part of saline is the minimum. Ideally, if we're doing one part of the blood to 4 parts of the saline, that'll increase our, you know, reliance.

If we get, if we use 4 drops of saline and we're still autoglutinating, that makes it a lot more comfortable. We've got the diagnosis, and it's not just that the blood's really concentrated there and actually giving us false results. Some people talk about if you get an equivocal result and one you're not entirely reliant upon, then you might say well actually do you take these cells, wash them in saline, and then see if they're still in saline and glutination positive.

Could take a bit longer to do and you know, might do other tests in there, but it's definitely an option as well. So I try to be brave and include a video, which is always a disaster. So on the left hand side, we should have what a normal in saline test should look like, so the blood moving across there quite homogeneously, and we're not seeing any sort of suspicus forming, and then probably spoiler alert on the right hand side, but this is how we're expecting our positive in saline.

So this is after a dog had about 4 drops of saline added on to the red cells, and you can see there, you know, we're moving across, but it very much looks more like silty sort of sandy material, and it's quite apparent there. So with that one I'd be relatively happy, what you can do is then pop a cover slip on or just have a look directly under the microscope and see if microscopically we're seeing them, you know, are we seeing that kind of really low on the left, or are we seeing the proper agglutination on the right, so we talk about macroscopic and microscopic or gross versus microscopic agglutination there. So we've done that and we've got our own positive.

You might want to do a bit further investigations, try and get a bit more of an idea. And the classic thing we talk about in these cases is looking for serrosites. So we'll all be aware from 1st and 2nd year at university, you've got your red cells and erythrocytes normally have that nice bi concave shape that kind of maximise their surface area for oxygen.

Because of that, when you look at them under the microscope, we get that darker rim around the outside alongside our central pallor, how they should appear normally. So in these cases of IMHA when we've got our B lymphocytes are thrown out antibodies against them, they're binding to our red cells, which then becomes a stimulus for the macrophages to recognise them as being abnormal, so we should be, you know, marking them to be optimised, so in other words, you know, digested. So the macrophage will come across and take a chunk out of them, and if it takes the whole thing out, then it'll be out circulation and contributes to the anaemia.

If it doesn't, then what'll happen instead is we take a small chunk out, but enough of the membrane and hemoglobins left behind, that it reseals and forms a smaller serrocyte. So if we're looking at these in 3D, they would look like proper spheres because the way they form now, just again, physic wise, probably a bit above my head about how the physics of it works, but they then become spheres rather than these bi concave shapes. And because we no longer have the bi concavity to it, we're no longer seeing a central parlour.

So if we look at the slides here, you know, we've got ones from the Wordsworth centre. You can see that really what you want is exactly as this picture shows, you want to get to an area where you're properly seeing your central parlour, and you know that it's a real thing. And then it means that When you're seeing these cells that are really definitely smaller than the others, which I'm sure you can appreciate, they're a lot more intense, and they're almost perfect circles.

So if we're seeing those, then we know that we're definitely seeing sphericites. If you look at an area where they're completely lacking the central parlour, then it's a bit trickier to definitely call them sernoites. And sometimes a few, the odd one can be normal in dogs.

Some breeds like the golden retriever can be born with a deficiency in one of the proteins inside there, one of the structural ones called spectrum. So sometimes they'll have a higher number of them, and you know, so just to bear in mind, again, more of the rarity rather than the rule. And if we look at our smear in general, we can also get more information.

So in these cases, we have our what we call the polychromatoils with the red arrows there. So these are cells that in effect the exact same thing as reticulocys, but without the new methylene blue staining, to show the reticulins still in there, we can't technically call them reticulates reticular sites, it's one of these sort of silly ones, but polychromatophylls would be called at the moment. We've then got our blue arrows that we could see, you know, they look like spirocytes again, they're quite small.

And the other one there, just bear in mind, you can see these ones that look like a sort of an empty bag for life. So these would be our ghost cells. So these are cells that the macrophages have taken a chunk out of and the hemoglobins escape from the inside, so we're left with empty shell from the outside, and they reform.

So they would be typical, more of an intravascular hemolysis, telling us the damage has been done in the circulation rather than out with inside the spleen or the liver. So usually those are the two tests we do and hopefully the majority of cases we're able to pick up with those two alone, where then something's left, these ones that are a little bit trickier when we think it's most likely the case, but not necessarily. So we can do a Coombs test and it just becomes a slightly fancier way of doing it.

So all we're trying to do is we know that these are the red cells we're removing from our patients. Have a lot of antibodies already bound to them. So what we're then doing is giving these cells a good wash.

We're then incubating them with antibodies that will then target the antibodies already bound upon the red cells. And the new antibodies we've added into there, the Cooms agent, they will then bind to other antibodies causing agglutination. And typically what we'll tend to do at that point then is the labs will often run at two temperatures, usually 4 and 37 degrees because some of these are more apparent at different temperatures and different labs and I'm gonna tell you about which type of antibodies might be involved as well and some potentially a prognostic information and doesn't really change what we do in these circumstances.

So you can sometimes get a positive cos test when you've had a negative and negotiation for a number of reasons, sometimes due to antibody numbers or how they're functioning. Usually if we're getting a positive insulin glutination we're very consistent with it, that's usually the first test we'll do as part of the Coombs test and we don't normally have to then send off for it because if we get a positive insaline we're convinced by. We're usually gonna get a positive Coombs test.

And sometimes it can be a few things that interfere with it, so dogs have had transfusions prior or if they're on any medications that could potentially interfere with the Coombs test. So we try and want to, before we're doing transfusions and medications, we really want to collect our samples and think about what tests might want to run in the next day or two just so we can bear that in mind potentially. And then the last thing is, you know, I'd say those are our three big tests that we really rely upon.

But sometimes we are looking at more supportive findings. So things like if we're seeing a dog, you know, if we get a 3 year old springer spaniel come in, it's got a hemoglobinuria, or, you know, we've got a nice clean stick from the blood sampling we've done, but it's very hemolytic, the serum at the top, then we're gonna be very suspicious. Again, if we've got this or haemoglobin, sorry, bilirubinuria, you know, to high amounts on a dog again would be quite suspicious in those cases.

The question is, so we've then got a diagnosis, it then continues a bit further, so we're then wondering, is this happening secondary to something else, which is often the case in the cat, whereas in dogs, the majority of them actually is a primary condition and we don't often find an underlying cause, particularly in these young spaniel breeds. So there's a recent consensus statement of course towards the end here and it evaluates which things are very, got very strong evidence they might be related to THAs and those that we don't have a huge amount. One of the things we talk about is anecdotally be certain medications, so the big ones would be the TMPS.

So we'd see, you know, there's potentiated sulfonamides, sometimes drugs like amoxiclab or the beta lactams. And cephalosporins are the ones people quite often talk about. The difficulty is probably some of the more commonly used, particularly the latter two, the more commonly used drugs.

So how often, you know, dogs will be receiving this and develop IMHA. It's unknown, but there's no real strong evidence. One definitely leads to the other, but something maybe bearing in mind if we're then going on to treat these cases later on.

We then look at infectious diseases, and the big one that we do have evidence for and the one that's got the most evidence behind it tends to be a bit easier. So usually Gibson a variety rather than the can we shown in that photo there, but we can come on to a wee bit about that later on, what kind of screening test we do. But some other conditions can also be, you know, related to whether they're definitive cause or not remains a bit unknown.

But things like leishmania, thanplasmas, or lia or heartworm and other ones that been sort of postulated to be involved there. And then neoplasms as well, so the big ones usually it's liquid tumours, so things like lymphomas, leukemias, multiple myelomas, you know, they can do whatever they like, so it's a good potentially could also cause these paraneoplastic syndromes manifesting as an IMHA. The one really to watch for is things like hemangiosarcomas, so they can often cause hemolysis, but usually because of the abnormal vessels the hemangiosarcoma tumour forms, means that the cells get lyzed or they get damaged on the way through, so we might see things like schistocytes or just a hemolytic anaemia, but actually it's not necessarily immune mediated in those cases, although it potentially could be.

And another thing we do is, you know, non-specific inflammation. So again, it hasn't really been shown to definitively be linked to IMHA. Quite often the difficulty is quite a lot of these things like these dogs will be on steroids, so how often they get secondary urinary tract infections.

We see pancreatitis relatively commonly in cockers, which we all see IMHA in, so how often these two things are together. And, you know, is pancreatitis causing inflammation, that upsets the immune system, that leads to MHA, or are you anaemic to a degree. Hypoxic, the pancreas is quite a sensitive little organ, so then it becomes pancreatitis secondary, so we don't really know, but sometimes, you know, it might just have a bit of a bearing on how you manage these cases if you know that's also going on at the same time.

So the question is what do we do then, you know, if we think we've got a case and we want a screening test, so our typical approach would be to question only in terms of travel history, just so we need to be aware of what the infectious disease should we be testing. So some of them we know we've got in the country, others maybe more likely from travel dogs. Is there a history of any medications or pre, you know, and how is the parasiticides, you know, preventative care as well going on there?

We'll often do full haematology to get an idea, you say you can look at MCHC, MCV, get an idea, we request a smear evaluation. We'll often look ourselves, we'll ask our clinical pathologist team to have a wee look as well, because they usually find slightly more subtle changes there. And then we're looking for a seed in biochemistry.

Some of the things like might help to look at like the supportive findings such as the hyperbilirubinemia, but it might often be do we have other comorbidities or things we do aware on that might just change which medications we want to give these cases. And then we'll often do 3 view chest radiographs, to check, do we have any underlying cancers process? Do we have anything untoward going on there, you know, anything metastatic.

And this is where we'll add on a lateral radiograph of the abdomen just to check, do we have a metallic foreign body in there that could be zinc, because until we get it out of there, these dogs aren't gonna get better, no matter what medications we give them. And we typically had an abdominal ultrasound as well, you know, check how that spleen and liver looks, and you know there's a lot of inflammation going on, there's quite a bit going on to these dogs, so it wouldn't be abnormal to find some changes, but. You might just want to know if you've got a big mass or something there that may just change the owner's opinion on what they want to do, you know, give a huge amount of money, and they can be really intensive cases to manage with varying prognosis, and if we know we've got something like a cancer underlying it, it may not definitively be related to the IMHA, but it may change what these owners want to do before they, you know, go down that route of committing.

And the other thing we'll often do is run a 4DX snap test and they're available from IDE, which for us costs about 18 pounds to the client, and they're looking for the plasma Elichia and Berelia antibodies and the diohyli antigen. So if it's there, there's a good chance we'll find it, but just bear in mind that because it's an antibody test, if we, Start testing these dogs before there's a chance for them to pseudo convert, we could get false negatives, so just because you get a negative wouldn't entirely rule it out there and equally sometimes you get the odd false positive as well. And just a word of mentioning, so we talk about these diseases and travel dogs.

The Bia is one of these ones that we do see, you know, there have been some cases reported down south in Essex. I think we've seen it as far north of the border at the moment, but it might just be that, you know, this is the one that we do have some strong evidence that potentially. Could be related to time and not necessarily the same type of beia, but it might just be something that if you're in an appropriate area you consider whether you add that to your tuning tests because again if it's something we can treat an underlying cause, hopefully a better prognosis for these cases.

And then we'll do a retinal exam, just to check, you know, is there suspicion for a choretinitis changes there. Sometimes these dogs seem to have higher blood pressure, you know, do we need to treat that, or have we got something else going on? And then again, the urine cultures we'll often do here, you know, have a look for a sediments, and the main reason is you know, it could be it's been caused by the the IMH's being caused by UTI.

For me, the main reason I tend to check them is just to work out if there's a unit tract infection there, and we're going to be immunosuppressing these dogs that just maybe I'm going to reach for antibiotics a bit sooner than just a chat with the owner and give them an early warning that there is a potential that we've got a life threatening condition, so we need to treat it, but equally we just have to be aware of this, and so they're keeping an eye for signs at home as well if they get to the point of being discharged. So we've almost survived, hopefully only on 2nd or 3rd wine by now. It's just talking a bit about the treatment and then we'll finish up.

So when they present an emergency, usually, whether they've got one red blood cell or they've got 1000 red blood cells, they should hopefully still be functioning normally, so hopefully we should still find that they're actually saturating these red cells, OK. So giving them flow by oxygen probably doesn't change that too much. It's more of these cases that are really bad, you know, maybe see them when they present really pale, completely collapsed, shocky because they're so anaemic, and while you're getting the blood stuff sorted to get into them, even if we can oxygenate a little bit of that plasma, then hopefully that's just enough to keep them on, you know, force, you know, from tipping over the edge.

And it's how you do that, you know, whether it's flow by oxygen, whether it's a mask or nasal prongs. I think the main thing is avoiding stress. If they're really hating it, then you might just to back off a little bit because.

If they're really using their oxygen demand just for breathing and keeping going, and then we start stressing them and making them poor or trying to move away, we're asking quite a lot of the muscle and oxygen demand for them to do that, just bear that in mind. And then finally, after being a pet blood bank presentation, we have to touch on the blood transfusion, so I'll talk a little bit about it in terms of how it relates to IMHA cases, because I think it'll be touched on elsewhere and some other webinars. So it used to be a controversy where people would say, are you just adding fuel to the fire by transfusing these cases, so by giving them the blood, are they not just going to lie through it and destroy it straight away?

And they probably are, but equally don't have much of a choice because if we don't do it, they're gonna keep going through their red cells till it becomes pivotal point. So really we're just trying to buy time where we can get the medications working and hopefully start to have a bit of an effect there. The thing really we have a bit of a chat with the owners at the beginning when these cases come in and just say that there's a good chance you're gonna need more than one transfusion, and you know, some of these dogs will need, you know, 4 or 5 transfusions and it's just how far thoseers wants to go and where finances are as well, and, you know, prognosis wise we're starting to get down the line, we're doing multiple transfusions.

What is the prognosis likely to be in those cases and having a good chat about, you know, what's involved in transfusion and the like. So the big question is always, when do we transfuse these cases? And there's not a, for me anyway there's not a set number, so people talk about transfusion triggers and where you would then start to reach for the blood.

And I think there's probably not an exact number for that. I think a big part of it is how is the dog coping with anaemia? Because we can have a dog that's got a PCV of 15% that's gotten there over the last month or at least a week or so, that's tolerating it pretty well, versus a dog that's dropped from 45 to 25 acutely, and actually that dog's much.

Had much less time to compensate and does need the bloods a bit more urgently. So we tend to go on whether they appear to be transfusion dependent or not. So we'll say, are these dogs tachycardic, are they chnick, you know, they've got an obvious weakness.

One of the blood parameters we can measure in the hospital is the lactate. So that tells us a bit about anaerobic metabolism, and we sometimes use rather than a one-off measurement, but potentially trending that to give us a bit of guidance and see. And then we know that a dog's been a, you know, it's a bit of a cheat for us because we're obviously seeing these cases as second as referred cases, but we know a dog was seen at their local bit yesterday and the PCV was, you know, 30 and it comes to us and it's 15 the following day, then we're to reach the blood a bit quicker because we know that this is something that's dropping a lot more acutely there.

And we blood take these dogs, so that's an ideal scenario in a lot of these cases and. Fully appreciate it's not always the case, you know, if you're in the middle of December in Shetland in the middle of a storm, maybe it's not going to be ideal to get a, you know, typed blood donor and all these things were of the kits available either. So typically what we want to try and do is type the dogs with their own, you know, blood of the same blood type as possible.

And the main reason is that there's lots of different and, you know, incompatibilities, but this is the main one that seems to be the most antigenic and the one that's most likely to give us a transfusion reaction. And if we're giving negative dogs positive blood, it might just be that, you know, we spend quite a bit of time and effort getting this blood into them, and it might last less amount of time than if we've given them a negative unit. So we see that typically, you know, ideally blood type and then give the appropriate blood type if we can.

If we're not able to, then we do might say that actually, if we can get blood from the donor and the recipient before we get the transfusion and hold on to that EDTA, and even if we can retrospectively blood type them, at least we know what they've had in case that has any. Inference. Another thing to just bear in mind with you depending on which kits you've got some of these rely upon you looking on a card or something to see if you've got a glutination present.

If you do have auto glutination already, then that's gonna make that a bit less reliable. So you might just have to think what you need to look at a different type of kit for there. And you're looking at about roughly about 35 pounds or so for those for the clients for us.

And then if we're down to choosing which product we want, so we know we've got anaemic patient and we want to see what's the best type of medication, or best type of blood to give them, ideally we're gonna want to give them a packed red blood cell transfusion. And that's because these, these patients have enough circulating volumes, they've got plenty of plasma, it's just the red cells they don't have. So if we can give them just concentrated red cells, it means we're not giving them additional volume that they don't need, and potentially if we're giving them, you know, lots of whole blood to get the red cells, same amount up, we could have given them with a smaller volume of packed red blood cells.

Then the concern is always that actually are we at risk of pushing these patients into volume overload, particularly if they're older animals, you know, if you've got these 1012 year olds cavies, then you might be a bit more, you know, actually the less fluid we can give them the better. And what we typically see is roughly 1 mL per kg of the pack red cells should increase the PCV by 1%. And there's lots of little calculations you can do to try and predict it based on the donor and recipient PCV, but at the end of the day, you can use what you've got available in order to, you know, try and get the PCV up.

And if we need to, you know, the patent red blood cells, we get our store currently in the hospital from the pet blood bank and available on request, and we know that sometimes, you know, we have had cases where they've needed the blood, so we've had them couriered in sometimes, you know, and then we can also ask them to blood type them if we don't have that available or cross match them to potential donors are a very good service for us as well. And they say sometimes you have to use the whole blood again there might be a blood bank, and if it, you know, you're in practise, maybe the only thing you've got available, which is, you know, definitely be better than nothing. We just keep a wee eye like I say, you just keep an eye on these patients that they're not gonna become volume overloaded.

So that would typically be things like are they developing a pseudo ocular nasal discharge. To become a bit more tipnick, you know, develop crackles on the lungs, you know, they see anything like that, and if those signs you might have to then maybe concurrently treat with resamide or at least monitor and back off on your fluids afterwards. Good, so I think more of the blood transfusion side in terms of side effects and all these kind of things will be touched upon elsewhere.

Can I finish up on what medications we give. So really the mainstay of treatment is the prednisolone. And typically starting doses are 2 to 3 milligrammes per kilogramme every 24 hours.

If we're looking at a lot of these patients, you know, they're not wanting to eat, they're quite flat, and we want to get the steroids into them quicker, so we'll often go for giving them dexamethasone. So because it's 7 times as potent as prednisolone, in order to do a conversion, all we'll do is work out our red dose and then divide it by 7 to give us a dexamethasone dose. And we might do that for the first couple of weeks, but then we're looking at as soon as we can really trying to drop the dose down to more of a 1 to 2 mg per kg per day in order to try and minimise side effects.

And the dogs that are the main Sufferers of the side effects tend to be bigger breed dogs, so we, if they're above sort of 25 kilogrammes or so, then we'll tend to do them based on their 1 metre squared body surface area. And although it doesn't work, it's quite a big dose, actually that's kind of all these ones often need and it hopefully minimises side effects that we'll see. And in these cases where you know that you're gonna be starting steroids, because again, sometimes on our finances and things won't limit us doing how much investigation we might like to do.

Often, you know, it's better to get them going. So what you can always do is, you know, take, have a chat with the owners and maybe you have some, you know, get as much of the diagnostics done first, or at least have a bit of blood in reserve. So if you want to run an extra test later on, if they suddenly get worse after the steroids, you can say, well, right, let's send off for it'd be easier now that we've got a sample there before they're being treated and the like.

And you know, counselling donors into the short and long term side effects. The next question is, when we've started our prednisone, it's what do we do then about when do we add in a second agent. And it's quite a personal decision.

I don't think we've got, you know, terribly strong evidence one way or another. The main reasons would be, you know, whether they're severe or life threatening illness, so how bad are these dogs when they get to you. And often we will start a second agent in the hospital here.

I think we're probably quite biassed because we'll see a lot of them trickier cases and ones that's done a very good job and they've already been on steroids, or we know they're very sick coming into us, so we know that we're gonna have to start a second agent earlier on. I think these ones that are sort of you know a bit more grumbling in the background, we probably don't see quite as many of those making our way in because they're managed very well in practise instead. Another one we might go on is if we're seeing it, so these are kind of more based on the guidelines and the current consensus statement, but equally, you know, completely valid, so if we're looking at does the PCB drop by 5% or more within 24 hours, or if we've been on steroids for a week now and the PCBs continuing to drop by 5%, are we then a bit more concerned and maybe have to add something else in.

Equally, every 7 days down the line, you know, a huge amount of effort going into things and we're still having to transfuse, you know, with cross matches and the like. It's now it's been more than 4 days in these cases, so we have to then cross match them before we can give more blood. So then again, you're looking likely to go.

And if we've got these big breed dogs that we know they're gonna get more likely side effects from the steroids, or if they've got concurrent conditions where we're worried about the steroid effect. You know, things like diabetics or cushyoids or something like that, we might say, well actually let's get a second agent in early, so hopefully we can get the pred out a bit quicker. And when we're looking at it, you know, next one probably down in the cascade wise, we'd be looking at cyclosporin, which interferes with lymphocyte function, so it's gonna interfere with the production of interleukin 2.

The main side effects we tend to see with this one are that you can get transient vomiting and diarrhoea, usually these ones that you just hold on to the same dose for the first few days, they do tend to spontaneously resolve themselves with that. They can get funny side effects, so things like become particularly hair suits so they can grow a bit more hair some breeds, or they can develop gingival hyperplasia where the gum starts to go down the tooth. This interferes, you know, could potentially be interfering with other drugs, if it's depending on the cytochrome B450, so bearing that in mind, and it's one of the few drugs that we can monitor therapeutic levels potentially if we wanted to, but because it's a, you know, quite a big gun drug, then there's also the cost involved in that to the owners.

One of the drugs we're using more in the last sort of recent time is a drug called mycophenolate, and this is a drug that interferes with the lymphocyte metabolisms that blocks the different parts of the nucleotides, it stops the lymphocytes forming quite as well. There's an oral formulation, but we can also have intravenous if we need to, and in humans it's often used as like an anti-rejection medication after transplantations. And dosage wise we'd say sort of 8 to 12 mgs per keg orally every 12 hours.

The biggest side effect and one that we definitely do see is gastrointestinal upsets and you know, bone marrow suppression reported, we don't see it. I don't think I've seen it myself personally, but the GI side effects can be the limiting factor in these, meaning we really do have to drop the dose down. If we're using the human formulations and actually it's relatively inexpensive for dogs, so you know, particularly if they're about 25 kilogrammes or so, the problem becomes in when they start to get smaller than that size or bigger, and then we have to then get formulated drug equivalents, and that goes from being less than 1 pound per tablet to, you know, 2 to 3 pounds per tablet or capsule, and so the cost obviously for the owners becomes a lot more, and that can really be the big thing that stops them to able to use this as a cost, unfortunately, which is completely understandably.

So an alternative we have same family as the mycophenolate would be azathioprine. So again, interferes with this purine synthesis, or blocking the lymphocytes. It can take a bit longer than the mycophenolate to work, depends on where you read and side effects wise we sometimes a bit more often.

So that would be bone marrow suppression, so we need to be checking our haematology relatively frequently when they're on this. But also our liver values so we can get a hepatotoxicity and it can also cause an acute pancreatitis potentially. The good thing is in terms of cost wise it's a bit more financially viable for a longer term, we can't give it to cats at all, and in the dosage down there at the bottom, but let's double check that.

And then There's a bit more of a shift, so omeprazo is one of these drugs that we've always used fairly frequently for different things and thought it's fairly innocuous. There's maybe some evidence that it can quite markedly upset the gut bacteria and potentially, you know, cause some problems there. So, again, based on sort of current consensus statements, we've moved away from using it as a routine thing.

We'll use it in these cases where we are really suspicious of ulceration. So we are getting Melina or our PCBs dropping, even though the agglutination stopped or it's like a non-regenerative. We might worry about that, then we might consider in those cases.

And the dosage we tend to use would be a milligramme per kilogramme, orally every 20 or 12 hours. The main thing is if you've been on this drug for, you know, any length of the time, then what we then have to do is just taper the dose over a week or two, because if we've blocked her. Acid production from the stomach, then we're gonna have a lot of gastro and all these mediators trying to increase that acidity of the stomach.

Problem being if we suddenly remove the omeprazole, you can sometimes get a rebound hyper aidity, so just for bearing in mind, and it can interfere with other drugs, so mycophenolate for it to get fully active needs to be converted by stomach acid. So it potentially could interfere with that being quite as effective, and if we're spending a lot of money on it, then we want to know what's doing the best job possible and equally it can interfere with how well clopidogrel functions as well. Coming on to that.

So as I said, probably one of the most common reasons these patients deteriorate acutely, and we've had one relatively recently, these dogs are doing pretty well, and all of a sudden they'll either become markedly dysneic, they'll become non-lying limb on a forelimb or hind limb, or they suddenly, you know, sudden death's also a possibility. And the most common cause for that can be thromboembolism. So these dogs are really inflammatory with IMHA.

We're then transfusing them, giving them steroids, which all these things actually increase your procoagulability that we have to do to get the dogs through it, but we can predispose them to forming more blood clots. And so what we often do is put these dogs on some kind of antiplatelet medication. So ADP receptor antagonist clopidogrel would be the most common one that we use, and dosage there would be sort of 2 to 4 milligrammes per kilogramme for dogs.

And again we avoid giving that with omeprazole because it can interfere with the efficacy. And usually if you were then having to plan, you know, sampling, you know, things further down the line like surgeries or anything, then we'd have to just bear in mind that we'd have to have that out of the circulation. And it's a bit more expensive, so another option would be again financially would be aspirin at a low dose and that would again same thing it can interfere with your thromboxan cascades, interfere with that, interfering with your normal platelet function and hopefully stop them being quite sticky and forming clots quite so easily.

The main thing is it's been shown that some dogs are what we call non-responders, so despite having an aspirin, they may not necessarily respond as we expect them to. But you know, in terms of financing things and it might be the only option we have available. So once hopefully we've given our transfusion, we've given our medications and everything's gone swimmingly well and no complications.

It's when the right time to discharge these patients are. And typically for me, I tend to go on is a plate, the PCV at least stable, ideally it should be improving, but is it stable? Are we seeing signs of strong regeneration there, so we want to see that reticular sites coming up to above 300 or at least getting towards that range.

We can have a look and see whether they've still got the ser sites and the gluttonation if they were present originally, but that wouldn't necessarily stop me sending them home. And just bear in mind there's probably still this process going on there and knowing that's something we want to, you know, be checking at follow-ups. So usually we then see these dogs back.

You know, after discharge, maybe, you know, a few days a week later, and if they're still nice and stable, probably have them on their current medication regime if they're doing well for the 1st 2 to 4 weeks. And then after that, what we'd start to do would be weaning the medications down if they're still tolerating. And normally what we like to do is, because the prednisolone's the one we often see more side effects with, we usually try and wean that down first, which is one of the nice things that we have a second agent on board to do a bit more of the heavy lifting.

So we typically drop the dose by 20 to 25% every 2 to 4 weeks, rechecking a PCV insulin and glutination and you know, at least on a blood smear in house, just to make sure things are nice and static. And if they are doing the next dose drop, and then following on from there, hopefully we've got them off the prednisolone, we can then start to wean off the second agent and see how they do. But we do warn these owners that recurrence is definitely a possibility, and that it could be recurrence as we're tapering drugs.

It could equally be recurrence, you know, 1 year, 2 years down the line, and because he responded once doesn't they may not respond just as well the second time, so they can be quite frustrating to treat treat at times. So, as I said, in the last few months, I think it was only just just before summer there, we've now got these consensus statements available, so one on how we go about the diagnosis of IMHA and the other how we go about choosing IMHA and they're fantastic, so they've got a lot of, you know, they've taken all the evidence available. And then try to make some guidelines and the very good thing is, you know, acknowledging where the limitations are and evidence that we've got, but also making suggestions of what seems reasonable in some guidelines and answering some of the questions I think we all have on clinics about, you know, what's the common sense way to do things versus, you know, what's evidence and what makes sense there.

So thank you very much everyone for listening, I very much appreciate you giving up your Monday evenings and we have to take any questions if anyone's got any. Craig, thank you very much for that. It was absolutely fascinating.

And it's lovely how you pulled it all together. For me, the big smiling point is that we had loads of questions. And as you went on, so I've been being able to remove them because you've answered all of them.

So well done on that one. You'd clear as much for a change, thank you. I'd also like to say a huge big thank you to our sponsors, the Pet Blood Bank.

Without their sponsorship, tonight's webinar would not have been possible. So, let's remember to support those who support us. And, you know, if you haven't used the blood, the pet blood bank in your clinic, give it a go.

They really are a group of incredibly helpful people. Even if you just phone them for advice, they, they really are very happy to help. And if you need blood, they get it out to you.

It really is amazing. Craig, a couple of questions we have. Zhao has asked, any association between IMHA and other immune-mediated diseases like atopic dermatitis and those sorts of things.

Yeah, it's a good question. We do sometimes see, so I don't think we've got any strong evidence. I think sometimes it will be that we know if certain conditions are going to be associated with, you know, just regulated immune system, like, you know, the ATPs or the classic ones, you know, we had a spaniel come in and think it was one year, it was IMHA.

The next year he had a thrombocytopenia that was immediated immune mediated and the following year, polyarthritis. So I think some of these cases are probably set up for that and that their immune system's probably just a bit disregulated and they are not, you know, recognising things the way they should do. Equally we sometimes get some conditions a bit controversial about things like lupus, where actually, you know, rather than just affecting one body system, they'll target multiple.

I think the evidence isn't terribly strong but if you get one, you want to get another, but, you know, it's something we definitely see. It can be a bit frustrating if they're already, you know, presenting with an IMHA they're already on treatment for steroids or cyclosporin as part of the dataic workup becomes a bit tricky about which step you go to next there. OK.

Lisa wants to know, a lot of people don't type at their first transfusion, and then they try blood typing or cross-matching for the second one. Is this not a, a false sense of security in that you, you're getting really poor readings because of the, the mixed bloods? Yeah, so I think it depends, hopefully, I don't know how much of a degree this sort of transfused blood will have an effect on that.

So I think it may well do. I think that's usually why we tend to, you know, I think it's pretty rare here, but you know, certainly was in practise, you get these circumstances where you've just not got the blood in, you know, if they're coming out of hours and what you're able to do. And I think in those cases, you know, definitely there's been times where we just have to give untyped blood because it's all we can do, and that's gonna be a thing that's life saving, and then we worry about this slight other things later.

I think we just know that particularly the DA1 is the one that's most antigenic. So if we know that could cause a problem and we've got the ability to type, then it's probably better to do it, and it means that at least if we're giving a negative dog negative blood, it should last a bit longer than if we're given positive blood. But I think, as I say, if we're looking at one of these ones where we're not entirely sure that we're gonna be able to, you know, do it at the time, at least if we get a bit of blood from the donor and recipient, and then, you know, take it later on, at least we know what we've done originally and it might just make us.

You know, take into account and at least, you know, hopefully in case there is any kind of impact of the transfused blood have an effect on the recipient, hopefully take out the equation by knowing what the kind of naive blood was like in the first instance. Yeah, I think that's a, that's a big one. And it's, it's really easy to do.

Just take the blood sample and keep it in case you need to use it later. Claire has asked a question. Is it necessary to treat with clopidogrel in cases of immune-mediated thrombocytopenia?

Yeah, so it's one we've been thinking about. So usually, because the initial stages with thrombocytopenics, they, there's probably a degree they've got low platelet numbers, but actually, platelet functions probably not fantastic in them either. So we tend to avoid clopidogrel to start with.

I must say at the moment it's not something we typically treat them with at all just now, and I think the worry is just that although we can be seeing a nice, you know, they're in with us and the platelet count's creeping up nicely. You just always worry a little bit that even if they go home and they are one of these dogs that relapses and we've then got them on clopidogrel, they could be dogs that were compensating OK with will count, but now we've interfered with their function a bit more. But I think it's something that actually have to consider because we've definitely had dogs that have.

You know, being treated for IMTPs and these immune mediated thrombocytopenias, and then we've then later gone on, gone home, and you know, we do get the odd dog that you do get a sudden death, and you do wonder, have they now the platelet counts now normal, we've still got them on the steroids and maybe had a few transfusions and they're a bit more inflammatory and very much like the IMHAs if they throw in a clot. And that's something you wonder where these slightly fancier ways of assessing the blood coagulation, like these are thrombo elastograms and all the things that we don't have access to at the moment, but things like that could be maybe be useful in working out when the tipping point is for adding something like that in. OK.

Barbara's got a great question. And here's the hot potato for you, Craig. It's, can you vaccinate dogs after they've had an episode of IMHA?

It is a good question. And this is one I think probably one of the more common advice requests you'll get actually after sort of sending IMHA dogs back into the world and making the horrible question yours back in practise. But I think the, I say at the moment, they've not got a strong link between vaccines and IMHA.

It's quite tricky because you think, you know, throughout the year, we're gonna have a lot of dogs given vaccines and a lot of dogs are gonna develop IMHA and we'll typically think that IMHAs have a bit of a seasonal look to them. So sometimes you tend to see a more sort of towards the end of summer, more into autumn, so whether, you know, that correlates with vaccinations. But there's no strong evidence there.

However, you know, we know that this is a disease caused by a dysregulated immune system, so anything we're doing that stimulates the immune system could potentially bring that on. So I think I must say we do slightly cop out and I think it's one that we can have a chat with the owners with and see what do they, you know, I suppose it depends because we definitely do still see leptospirosis here, still relatively commonly, and we'll see parvovirus here every so often as well. And this is, you know, his second opinions and referrals, so you know, first opinion, I think we see just as many if not more, particularly the parvos.

And it becomes which of these conditions is more life threatening. So we typically have a chat with the owners, you know, things like, do they want to go down the route of tighter testing, or do we accept that if you're in a sort of lepto or power of hotbed area, you give the vaccine knowing that it could stimulate the immune system, but the bigger sort of risk becomes picking up one of these diseases and a naive dog potentially. But I don't think we've got a strong, and again, the consensus kind of goes into that a little bit, but there's not a.

Say right or wrong answer, which is why we normally go through the pros and cons with the owners and really sort of kind of counsel them and see what they want to do on that. So very sorry, Barbara, it's classic cop out unfortunately we can't give an exact answer on it. Right, last question for tonight.

We've had loads of comments coming through of people saying, excellent webinar. Thank you very much. But last question we have tonight, how long would you realistically expect for the PCV to take to creep back into the normal range?

So I think usually we'll see it within sort of 1 to 2 months and one of the sort of phenomenon we can see relatively frequently actually is you get a PCV that's, you know, it takes a wee while to get itself going and it's, you know, maybe the low teens after we've transfused and it starts to creep up into the 20s. And then we'll then say get to the high 20s, low 30s and then hang around there for a while. So that's why we tend to say that if we're seeing that, we'll keep the prednisolone and dose, you know, keep weaning them as long as it's static there.

And I think there's some maybe evidence now and some people are talking about is actually that once you get to that point there, it's no longer the IMHA that's causing the problem, cause a lot of these dogs are then a glutination negative and their spirit of sites have gone. But they're still anaemic to that degree, and it's whether actually we're then getting, you know, because we've been on steroids for a good couple of months at that point, do we then have, you know, a bit of sort of subclinical gastrointestinal bleeding, so your regeneration kind of matches what you're losing through the gut. And then as you start to wean the tread down, that effect goes, and then the PCB continues to creep up there.

So usually within 2 months we'll kind of see it above the 30 level most often. And then hopefully it continues to do that and we'd keep weaning the steroids at that point. You just don't want to see the PCV dropping dramatically as you sort of wean further and that's why we'll often recheck the PCV to solids a glutination kind of before each further drop in dosages there.

Excellent. Craig, I can thank you 100 times, and it won't be enough. Your time tonight has been well spent and certainly clearing up some of the, the, sometimes complicated bits of, of IMHA and, and you've really made it very easy for us to understand.

So thank you very much. All that with a Scottish accent. So thank you very much.

Apologies if I got ununderstandable at any point. And once again to Pet Blood Bank. Thank you so much for your kind sponsorship.

To all of you that attended tonight, thank you very much. Libby, my controller in the background. Thanks for making it all possible and from myself, Bruce Stevenson, it's good night.