Video of Immune Mediated Haemolytic Anaemia (IMHA)

Thank you very much, Bruce, and thank you everybody for logging in and joining us tonight. So tonight we're gonna talk about immune-mediated hemolytic anaemia, and this is one of my favourite topics. It's something that we commonly see in practise, and it's something that as nurses we can really get involved with.

So we'll start with the basics, so what is IMHA? So this is a condition where the immune system starts to attack the body's own red blood cells. So it thinks that the red blood cells are foreign and it starts to destroy them and it therefore removes them from the circulation.

Now IMHA targets all types of red blood cells of any age, and the normal red blood cell lifespan is between 100 and 121 days. So the majority of the content of this talk is taken from the ACIM consensus statement, which was released in 2019, just earlier this year. Now I have put the links to this in the notes that you'll receive from the webinar vet and I would encourage you to have a read.

It's quite long, but there's two different ones, one on treatment and one on diagnostics, and it's the most. Up to date information and a consensus statement is basically they get a load of specialists together. It's all evidence-based medicine or it's opinion from their experience, and they put together the best course of treatment.

So it's all up to date, it's all relevant, and it's all, it's really interesting to read. So here we'll talk about primary and secondary IMHA. So in brackets we have associative and non-associative, and that's because we used to call them primary and secondary, but now we believe that it's quite difficult to determine what's primary and what is secondary.

So is the IMHA secondary to another condition, or is was the condition. There first and it's quite difficult to determine what was first and what was second. So now we say if it's primary, we now call it non-associative IMHA and that just means it's not associated with another condition.

And the secondary we now call associative IMHA and that just means it's associated with other diseases or conditions. So the other conditions that it could be associated with could be infectious diseases such as Mycoplasma hemophilus, common in your cat. Babezia, Leishmania, neoplasia.

So there isn't actually a link between neoplasia and IMHA, but it's been on the list to say could be a trigger. Drugs or toxins, so zinc seems to be a little bit more commonly seen in the US because a lot of their coins are made from zinc. Could be an inflammatory process, and we do have vaccination on here because we do believe that some patients have been seen to develop IMHA after a vaccination.

There's no evidence to show that it's linked. But if IMHA has developed within 6 to 8 weeks of vaccine, then it could well be on the list of potentials, but there's no proven evidence as of yet. And I would say if you do have a patient who has had IMHA in the past, it's still safe to vaccinate, but you might just want to check the teeters and just check the bloods before you go and vaccinate to see if it's necessary every year.

And you can just err on the side of caution, but there's no proven evidence to say that it was caused by this, and if it weren't caused initially, then it's unlikely to be caused a second time around. So you should be safe to vaccinate these patients. OK, so a little bit about The antibodies and the antigens.

So what is an antigen? So this is a molecule that can trigger an immune response, and each one of these has a distinct feature leading to a specific response. So then we have an antibody that is released in response to the antigen, which is also known as an immunoglobulin.

This is a Y-shaped protein and it's produced by the B cells of the immune system. So once we're exposed to an antigen, antibodies are produced and each cell, they work kind of like a lock and key mechanism because each antibody is produced specifically for that antigen. So that is the only thing it will target and that's the only thing that it will remove from the body.

OK, so antibodies directly target the red blood cells when we're talking about primary IMHA and whereas secondary is slightly different. So if it's caused secondary to a mycoplasma hemophilus, for example, the little bug might have attached, it will have attached to the red blood cell, and this is why the body will start to see this as a foreign antigen and will start to get rid of those red blood cells and when it's trying to get rid of the bug, it will take the red blood cell with it. If it's a type of bacteria or something else that's attached to the red blood cell, even if it's not there at that present time, if it's been attached to that red blood cell, it will have damaged the cell wall.

So therefore our antibodies will see it as damaged and it will destroy it and get rid of the red blood cell completely. So. That's how it's slightly, it differs slightly from primary or secondary.

So if there is an associated disease, then it's because it's attacked and damaged that red blood cell, and that's why the immune system will get rid of that red blood cell. Whereas primary, it's just the immune system actually attacking the red blood cells, and there's nothing wrong with them. OK, so first of all, we talk a lot about hemolysis because that's what happens.

So the red blood cells hemolyze, and so I just wanted to put in what is hemolysis, a little bit of . We can talk about the definition. So hemolysis literally just means the destruction of a red blood cell.

So we have extravascular hemolysis. This is more common, it's less acute. And usually these are the patients that come in and they are jaundice because they have a hyperbilirubinemia and they have spherocytosis as well on the smear.

So this just means that small, quite round red blood cells, they tend to lose their biconcave shape and their central pallor and you quite often will see these with the patients with IMHA. Whereas intravascular hemolysis is less common, and the antibodies attached to the red blood cell, which causes an influx of fluid to enter the cell, and that's one way that the body will encourage this to happen, so that the cell will rupture. And that's how they try to destroy the cells and get rid of them.

So the fluid is just sent in, causing it to rupture and then the body will get rid of that cell. So this does have a more acute onset and you often see hemoglobinemia. And it does also carry a poorer prognosis.

So we will talk about the extravascular hemolysis, which is more common, and the primary IMHA the majority of this talk. So all of the further slides are mainly about primary IMHA. OK, so what type of breeds do we see these in?

So as you can see here in this image. Springer spaniels are really, really common. Cocker spaniels equally as common.

Bon frise, miniature schnauzer, your miniature pincer, and rough collie. So the ones that we tend to see are your springers and your cocker spaniels. We have 2 in work at the moment, just today.

So in dogs, they tend to be young to middle age. It doesn't carry with any sex or pre pre predisposition, but usually we see them in neutered patients and the average age is around 6 years old. It's much less common in cats, however, if you do see it, usually they present a lot younger and it tends to be males that are overrepresented in cats.

Whereas there's no set link in dogs. OK, so it's important to get a really good history from the patient, from the owner, so that we know, has this patient travelled abroad, because a lot of the infectious diseases that dogs can carry mainly are from abroad. They're not endemic to this, this country, to the UK.

So it's important to get a really thorough history so that we know exactly what we're dealing with, and we can try to differentiate, is this a primary cause or could it be secondary to an infectious disease or some other kind of. Condition. So we quite often see jaundice in these patients, and the reason for that is because our red blood cells carry haemoglobin.

The haemoglobin gives the red blood cell its colour, and as the red blood cell is destroyed, it releases the haemoglobin into the bloodstream. It's taken to the liver, which is where it's converted into bilirubin, and this is when we start to get our yellow jaundice colour. So the liver can quite easily become overwhelmed because of the amount of haemoglobin that's having to convert to bilirubin.

So it is quite harsh on the liver, this condition. However, they're not jaundice because of a liver issue. They're jaundice because of the the rupture, the hemolysis of the red blood cells themselves, causing the release of that haemoglobin and the conversion into bilirubin.

So they quite often come in, they might be lethargic or just be weak. So weakness is quite common with anemias, especially if the PCV does drop quite low. Anorexia, they're likely to be pale.

Sometimes you'll see vomiting, and they may even come in collapsed and occasionally you'll have a discoloured urine, so it might be quite dark in colour because of that bilirubin. So, I'm gonna talk a little bit about the clinical signs that you might see, explain why we see them and what we can do as nurses to try and triage these patients and try and keep them as comfortable as we can. So we will see pale mucous membranes because of an anaemia.

We will see, we're likely to see a tachycardia and a tachypnea, and that's just because our red blood cells carry our oxygen. So if we have a decreased oxygen carrying capacity, our body will try to compensate for that by increasing our respiratory rate to increase our oxygen intake, and our tachycardia to try and pump that, those, we have a decrease in our. Red blood cells, so we need to work harder to try and get those red blood cells to all of the tissues and to all of those organs.

So that's why you might see a tachycardia. So because we do have a decreased oxygen carrying capacity, it's essential that we're providing oxygen to these patients. So quite often people will, will think, oh, if this patient is dyspneic, we'll put it in oxygen.

If a patient is anaemic, it needs to be on oxygen also because all of those cells that we do have, it might be a decreased number, but it's really important that we saturate them with oxygen as much as we possibly can. Just to help them, to help prevent any hypoxia to any organs or any tissues and just to help this patient along with its oxygen saturation. Now, if you do have a multi-parameter machine or a pulse oximeter, link this up, it's a really great tool.

However, it is likely to be 99 to 100%. So quite often people think this is likely to be decreased because our oxygen carrying capacity is decreased, but a pulse oximeter measures the saturation of each cell. It doesn't tell us anything about the amount of cells that we have.

So each cell is likely to be saturated to 99 or 100%, especially if the patient is, is receiving oxygen. So just be aware of the limitations of a pulse oximeter. Still use it and it will tell us if the patient starts to desaturate, but just be aware of its limitations.

If you do have an ECG absolutely link it up. It might be totally normal, depending on the severity of the hypoxia. So if you do have hypoxia, one of the areas that it can affect is the, the heart, the myocardial muscle.

So you could see abnormal complexes on your ECG and that could just be because of areas of hypoxia to the myocardium. So if you have different areas of hypoxia, the heart can throw a lot of abnormal complexes, not necessarily all of the same type. So you might see a massive range of abnormal.

Complexes. And when you look at the ECG, you think, oh my God, what's going on with this patient? And it doesn't follow a consistent theme, and that's because it's from hypoxia, it's not from a cardiac issue, it's not from any electrolyte abnormalities.

It's because there's a lack of oxygen to that heart, so it's actually caused some hypoxic damage. The most bizarre ECG I've ever seen is from an IMHA patient, and that's just because of the severity of the hypoxia that was seen in this patient. And bounding pulses, so this is just the circulation trying to compensate.

So we can do blood pressure to check what's going on with these patients. So quite often we expect if a patient's anaemic, it might also be dehydrated, and that might be the case. Quite often these patients are in a fluid retentative state, so because we do have a decrease in those those red blood cells, the body is more likely to keep hold of some fluid and retain it.

And that just helps the perfusion to try and get these, this red blood cells around the bloodstream and to all of this, the organs and the tissues, so it just helps with perfusion. So these patients aren't necessarily going to be dehydrated. However, it will give us a good indication as to how the patient is coping and how it's compensating, because if the PCV is really low and it's now gone past the point where it's really struggling to compensate, then we might start to see a decrease in our blood pressure, so it's definitely a really good tool to use.

Jaundice we've mentioned earlier, weakness and collapse again because. We have a decrease in our oxygen carrying capacity if this patient has walked outside for a week, it's increasing its oxygen oxygen demand. So it may well be weak have weakness and it could also collapse just from the simplest of tasks.

And we may hear a low grade heart murmur. So these are usually grade 1 or 2, and it's a hemic murmur. And the reason we hear it is just because of that change in viscosity in our blood.

Usually once the patient improves and the blood, the red blood cells are increased, then this murmur disappears, simply just ahemic murmur. And our blood plays an important role in our thermoregulation, so these patients might be hypothermic when they present. OK, so a normal PCCV for a dog, 35 to 55%, and a normal PCV for a cat is 25 to 45.

Now it's important to remember these values. We've had a few patients referred over to us, cats in particular for anaemia, but the PCV is 27, and I think people quite often forget that a cat's PCV is naturally as low as 25, and they often just remember the figures for a dog. So if you're gonna remember any figures from tonight's webinar, try and remember these, the cat and the dog PCV.

And it's absolutely vital that we're always assessing a total protein alongside. So our PCB tells us a lot about our hydration status, but we should be looking at our total protein to see, to have a look and see about the patient's overall status. So if the patient's PCV is slightly increased, our total protein will also be increased if it's dehydrated.

If the PCV is decreased, is it because of hemolysis? So is it. A cause such as IMHA causing hemolysis, so in that case we would have a decreased PCV but our total protein is likely to be totally normal.

Or could it be that we've got an acute blood loss, so maybe our patients on steroids or non-steroidals, it's got an acute GI bleed from a gastric ulcer, and is the PCV dropped because of that? And if that's the case, then the total protein will also decrease as well. So it's really important that we are always running a total protein alongside the PCV.

And the PCV is always more accurate than a hematocrit, so we should always be doing this, and especially if a glutination is present. So you can also assess the colour of the plasma on the sponge tube, so you might see if it's if it's icteric or it's jaundice. And usually the anaemia is quite severe and we might see a mean of about 13% in a PCV.

So we had a dog in yesterday whose PCV was 7, so that's the lowest I've ever seen. So they can go incredibly low with this condition. The mean is around 13%.

So every time we do a haematology, we should be doing a fresh blood smear and for this condition, especially because this is how, this is one of the reasons that we can use a blood smear to diagnose this condition. And if anything on our hemogram is abnormal, we should definitely be doing a blood smear then. So if you're not used to doing blood smears in practise, practise makes perfect.

Start doing it now, start doing it on your normal patients, patients who aren't anaemic, and then you'll be good by the time an a anaemic patient comes in. So just keep on practising and then keep on having a look at these under the microscope to get used to what normal cells look like so that you can see when a patient comes in that's abnormal. OK, so it is important when we have any anaemic patient that we are looking at a blood smear and the one important thing that we can do is assess, is it regenerative or is it non-regenerative.

So just meaning is the bone marrow regenerating these red blood cells. So IMHA is strongly regenerative. And regenerative anemias are either caused by hemolysis, so IMHA or another condition that could cause hemolysis or haemorrhage.

So that slims down our differential list for our anemias quite dramatically because our non-regenerative anemias are totally different causes. So if you know that this has a regenerative anaemia, then you're onto a winner. You know that you've got only two things to consider.

So you might see a variation in your red blood cell size and a variation in the red blood cell colour. And you could also check your reticular cys either if you have a new methylene blue stain or just check it on your machine. So we do have an image here.

So this is your regenerative versus your non-regenerative. So if we look at the non-regenerative on the right, you can see that they're all a similar colour, similar size, and just overall, as a quick glance, they all look pretty much the same. Whereas on the left you can see that there are different sizes, different colours, and if you're unsure whether there are different sizes, cos it can be quite difficult to look at, just find the smallest cell that you can see.

So. I don't know if you can see my mouse here, but maybe this one is the smallest one, and then look for the biggest one, so probably this one here, and then compare those two sizes. So that is quite a dramatic difference in size.

So this is likely to be a regenerative anaemia. OK, so as nurses I'm sure we've all been asked to do an insulin glutination test, and this is for the diagnosis of IMHA. So for an insaline agglutination, you can see a great image here of a glutination on the side.

So usually this just looks, if it's not agglutinating, you put your drops of 4 drops of sodium chloride or saline, and it does need to be saline. I've had people do this with water for injection before and it doesn't work. In saline, a glutination has to be saline.

And the blood has to be EDTA. It can't be fresh blood and it can't be from heparin. Must be EDTA to give it a good mix.

Put one drop of blood on with 4 drops of of saline. Now I learned that you do 1 and 11 drop of saline with one drop of blood, but in the consensus statement they've said that it's much more accurate if you do 4 drops of saline. So it actually takes it up to 100% accuracy, and we'll go into that on the next slide, so it is much more accurate.

So you just rock the sides, so you put your saline and your blood on, you rock the slides from side to side. If there's no agglutination, it just looks like a nice pale red solution. Whereas if it is agglutinating, they describe it as a sandstorm effect.

So you can see here it's really sandy and grainy, and that's the agglutination happening in front of your eyes. So you can look, if you can see it on the blood smear, sorry, on the the slide in front of you, this is called macro agglutination, just meaning that you can see it with the naked eye. If you can't see it, this can't rule out that your patient doesn't have that, doesn't have IMHA.

You need to look under the microscope and then you might see micro agglutination. And that simply just means it can't be seen by the naked eye, but it can be seen on the on the microscope. So you need to remember that rulelo formation is normal in cats, and this simply just means the stacking of red blood cells.

So usually they stack in a bit of a line, whereas in a glutination is more of a clump. So that's one way of differentiating between the two. So this has a 30% sensitivity, so there are 30% of dogs out there that you'll do this test on, and they will, it will have a negative in saline glutination even though it has IMHA.

So when you put 4 drops of saline with one drop of blood, it's reported the specificity is 100% for IMHA. So if this is positive for glutination on an insaline agglutination, 100% this patient will have IMHA. It can't be from any other condition.

But if it doesn't have an insanine agglutination positive, it doesn't mean that it doesn't have it. So if it does have the agglutination, it's associated with a poorer prognosis because it means the glutination is where. And you can repeat the test with washed cells to be more accurate.

So we also send off a Coombs test, and this is just a mil of BDTA blood and this tests for antibodies or complement on the red blood cell surface. So the sensitivity is around 70% for dogs and up to 82% in cats. And it specificity, meaning it's specific to IMHA is also quite high.

So if you have a positive Coombs, this means that your patient does have IMHA. So try to test for a Cooms test before the patient is on steroids. However, it will take a couple of days for the steroids to start affecting the test.

So if your patient's on steroids and you start to control the IMHA and then you do a Cooms test, it should be negative because you should be controlling that, the agglutination. But it can take a couple of days, so you're fine up to maybe 6 or 7 days to still take this blood and send off for a Coombs test even if your patient has started the steroids, but you just need to make the lab aware that it's already on steroids and bear that in mind when you're interpreting the result. OK, so what changes might we see if we run a biochem or if we do some urine analysis.

So we might have an increase in our haemoglobin, and that's as we mentioned earlier, that's because our red blood cells are rupturing and releasing that haemoglobin. We might see an increase in our in our bilirubin again because the haemoglobin is converted into bilirubin by the liver. If an increase in our bilirubin is present, then it does carry a poor prognostic indicator.

And we might see an increase in our liver values to our alkhos or our ALT and this could just be because it puts so much pressure on that liver trying to convert so much of this haemoglobin into bilirubin, that it's quite stra it's quite a strain on that organ, so we might see an increase in our liver values. And if we have an increase in our BUN, this again is a poor prognostic indicator, so this could be from a hyper perfusion if that's present, or maybe even just a hypoxia. And a decrease in ourmen is also quite common.

So if you do a urine sample, again, you might see an increase in our haemoglobin and our bilirubin value on our dipstick. OK, so we can run COAGs, and it is recommended that we run COAGs. We can have conditions such as Evans syndrome, which is the combination of IMHA and IMTP.

So if you have both of those together, it's classed as Evans syndrome and. Excuse me, for this, you can do a platelet count, and do a couple of other tests, but you can also test your coagulation factors. But the main thing to remember about your coagulation system is that these patients are in a hypercoagulable state.

So these guys are at a high risk of throwing a clot and throwing a thromboembolism. Now we tend to find that if the patients, even in the most sick patient. If they get better with this condition, if a patient's going to die from IMHA, the most likely cause is because they've thrown a clot.

So it is a really high risk for these patients. So it's more likely to kill the patient than the actual disease itself. So it's important that we do try to rule out any of these secondary causes.

So there's a list here of multiple things that we can do, but we need to just bear in mind, gauge this on the individual patient. So if a patient does have, you know, it can have a neurological examination if maybe gotten a stagmus. So I've seen patients with IMHA come in and they've had a mild nystagmus, and that could just be a sign that they've thrown a clot to the brain, .

They can also throw the clot to the lungs or to many other areas, but it's important that we're looking for, we're utilising different diagnostic tests so that we can try and rule out whether this is a primary or a secondary cause. So radiography we might want to do an ultrasound. Typically in your referral centres, we might do a CT and also an ultrasound of the abdomen as well, just to rule out any other abnormalities, check the spleen, check the liver.

And then urinalysis, culture and sensitivity usually will do from a cystocentesis sample, but there are many other, tests that you can do depending on how the patient presents. OK, so I, I'm not gonna go into the infectious diseases of dogs because we mentioned a few of those earlier and usually they're the conditions that aren't found in the UK, so they're only relevant if they've been abroad, whereas cat, this can be caused by feline infectious anaemia, so mycoplasma hemophilic. Common in your kittens, FIV FELV, FIP, or leishmania.

So all of these could be a primary cause which can trigger a secondary IMHA or an associative IMHA. So it might be useful to screen for some of these infectious diseases if you have a cat in. OK, so how do we treat this condition?

So prednisolone is our go to drug. So usually we'll put them on a 6 month dose of treatment. And we tend to find in a referral hospital that if this patient relapses, relapse is quite high rate anyway, but if they do relapse quite often it's because they've been weaned off the Pred too early.

So it's important to remember that they usually need 6 months' worth of treatment, so it is quite long and it's it's quite long for the owner. And then we usually ta by about 2 taper by 25%, say about every 2 to 4 weeks, and we need to advise the owner on the side effects of this. So any patient that goes on steroids is likely to develop PUPD, polyphagia, they might get a pot-bellied appearance, and we've got another slide to describe any of the side effects, but I tend to find that.

Depending on what condition this is used to treat, quite often the owners will come in and say, I think he's suffering. He's weeing in the house when he didn't used to. He's got an increased thirst and he's urinating loads, he's eating tonnes, and usually this can be quite distressing from the owner's point of view.

And if they're going to opt for euthanasia, it's usually because of the effect from the prednisolone from the steroids, rather than the actual condition. So it's important that the owner is warned of these side effects before putting the patient on steroids, just so they know to look out for them and be aware that PUPD is not necessarily a sign that the patient is suffering and that it will get better when we start to taper this drug down. It can take between 2 to 4 weeks for full effect, and we have seen some IMHA patients take a little bit longer than that.

So you can also use dexamethasone if the patient won't eat or it won't tolerate medication, but it's no difference in strength to your prednisolone. So it's not more potent just because it's going IV or IM, but it's just another option there for if your patient is not ideal for oral men. So some of the side effects, because you do have to use such a high dose of prednisolone, the side effects can be severe and usually in the large breed dog, they tend to get it quite worse just because of such a high dose of prednisolone.

So you might start to see some muscle wastage or weakness as seen in this picture on the, the patient's head. Lethargy, as you mentioned, PUPD and polyphagia, you might start to get the pot-bellied appearance because it weakens the muscles, so your patient might start to look Cushingoid like the picture at the bottom. They could start to develop diabetes, and we all know that prednisolone can make us more likely to develop a gastrointestinal ulcer.

So there are a lot of side effects from prednisolone, and that is why we quite often introduce a second drug alongside. And the reason for that is just so that we can lower that glucocorticoid dosage to minimise the side effects. So these can be introduced to any patient from the outset.

You don't have to wait, you can put any IMHA patient on two immunosuppressant drugs. And again it's just to decrease that overall dose of the glucocorticoids. Now there's no proven benefit that an additional immunosuppressive therapy works any better, but the side effects do seem to be a lot less severe, so we do introduce a second drug anyway.

So here's a few points on when we might consider that second drug. So if the patient has a severe or an immediate life threatening disease, so maybe the patient has a PCV of 7, and that is, that is a life threatening condition, we need to act quickly, and this is maybe a patient that will start to think actually, put it on two different immunosuppressants on the word go. PCV, if that doesn't remain stable, or if it decreases by more than 5 within 24 hours, or if it decreases during the 1st 7 days of treatment with the glucocorticoids.

So if the glucocorticoids still don't seem to be doing their job by suppressing the immune system, then you can introduce the second one. And depending on the blood transfusion after the 7 days of treatment. So if they still require a blood transfusion after 7 days of glucocorticoids, then introduce a second drug.

But also if they develop or they're expected to to develop any severe adverse side effects due to glucocorticoid, so maybe they've had some in the past and they haven't really reacted very well. And this is particularly relevant in patients who are over 25 kg in body weight just because that dose is so high, we're putting them at really high risk of these side effects or a gastrointestinal ulcer. So for these patients, we would always just put them on a second drug.

So some of the other drugs that you can use azathioprine, after 2 to 3 weeks, the dosing interval may be increased to every other day. Until it's discontinued, you can use cyclosporin, mycophenolate. And we do also recommend that these patients go on thrombosis treatment because as we mentioned earlier, these patients are at very high risk of throwing a clot.

So if the patient is likely to die from IMHA, the most likely outcome is because it's throwing a clot somewhere, whether it be in the lungs, the brain, any other area, then this is the most likely cause. It might cause dyspnea if it's being thrown to the lungs. It could cause renal dysfunction if maybe we've got some clots in the, in the kidneys, and it can kill your patients.

So it is a life threatening condition and it's something that we need to treat. So put these patients on antithrombotic drug. So the, the drugs that are available are aspirin, clopidogrel, heparin, low molecular weight heparin.

But the one that we recommend is clopidogrel, and this should be used between 2 to 4 milligrammes per kilo per hours just once a day. And this is the drug of choice as per the consensus statement that's been released this year. So the other drugs are available, however, this is the one that we should ideally be choosing.

So these patients are on really high dose of immunosuppressant. So you might think why are we going to bury a nurse them, but it's more for their safety rather than ours, so they're really immunocompromised. So if we're going around and we're touching millions of different patients, and then we go to these patients, we're putting them at risk.

So it might be worth just popping a sign on the front just to say wear gloves and an apron when you're handling this patient and just take extra precaution when you're dealing with the IV catheter or any injection. Maybe you're popping drugs through the given set, just be extra cautious with these patients because they are really immunocompromised, so they are a higher risk. OK, so I'll talk briefly about some transfusion triggers and we'll go through transfusions a little bit, but as Bruce mentioned earlier, I've also done a talk about two weeks ago for Webinar vet on transfusion medicine.

So it will be useful to have a look at that, and it goes into blood transfusions in much more depth than what I'll be covering tonight. So some transfusion triggers, when do we give a patient a blood transfusion? So we need to look at is this an acute blood loss or is it chronic.

So quite often our chronic patients can come in and they'll cope really well. So maybe it's been a chronic anaemia that's taken a few weeks, a few months. And these are quite often the patients that you'll see with the lower PCVs, say, a dog with a PCV of 10, for example, but yet they seem to be coping an increased respiratory rates and they're a little bit weaker, but the body has had time to get used to that decrease in the red blood cells, so they tend to be a lot more stable.

Whereas if a patient's PCV drops to 10, acutely, they're likely to be collapsed, dyspneic, and really, really sick. So it's important that we weigh up how quickly the patient is losing this blood. And also cats tend to tolerate lower PCVs much more than dogs do, so cats can go down to 7 and still be relatively, Well, I wouldn't say stable, but they're coping quite well, whereas a dog quite often becomes dyspneic anything below 10.

And also we need to bear in mind the rate of the ongoing losses, so have we detected anaemia and we're likely to, once we put them on treatment, it's likely to stop decreasing from then on. And therefore do we need a transfusion depending on how low it is. Or do we have a patient who's likely to carry on losing more blood and in which case we might need to get this on board pretty quickly.

And we can also look at our tissue perfusion. So does it look like our perfusion is decreased? Do we have a pre-renal azotemia?

. One thing that we can use is our lactate level, so if you have the ability to measure lactate in-house, whether it be an individual lactate monitor or maybe on your epoch, this is really useful. So lactate becomes increased with decreased perfusion or also a a level of hypoxia. So if we have a a patient who maybe is dehydrated as well as anaemic, and then we start our therapy, so we give them fluid therapy, this should help with that perfusion and therefore that lactate value should come down.

So that's quite useful to keep reassessing and it also gives us an idea on what fluid rate we should be using. So if our lactate level is not coming down, we need to worry a little bit more and say, OK, is this from hypoxia or is it from the hypo perfusion? Because if so, look at what fluid rate our patient is on, do we need to increase it because our perfusion doesn't seem to have improved.

So it, it is a really useful indicator. And also what other treatments is the patient needing so is the patient likely to go for sedation and further investigation, in which case it might need that help from us to increase those oxygen carrying cells, and if it's gonna have an anaesthetic, maybe it does have a gastric bleed or. Some other kinds of condition that's caused, causing the haemorrhage, then we need to ideally get blood on board before it goes and has an anaesthetic or surgery.

And also does it have a concurrent disease and therefore a concurrent comorbidity. So is this patient 15 years old and it also has diabetes and pancreatitis? Does the patient want to go for a blood transfusion?

So there's are many different things that we can look at to assess if our patient is suitable for a blood transfusion. But it's important that we treat, treat each patient individually and transfuse according to the clinical signs rather than the blood result. So usually, as a rule of thumb, we'll say consider a blood transfusion with a PCV below 20, but we would strongly advise below 15.

And we need to just assess each patient. Is the patient coping with the anaemia? It has a PCD of 20, but it's coping really well and with the treatments, it's likely to improve.

So the options that we have are we could give it a whole blood transfusion, or we could give pack of blood cells. Now, whole blood is quite difficult because you need to find a suitable donor, you need to bleed the donor, make sure it's a suitable mass, do all the tests to make sure what it is and also. Provide that blood to the patient who has the anaemia in time, so whole blood can be used, we'll pack your blood cells or the drug the blood of choice for that reason.

Now pack red blood cells contain red blood cells and anticoagulant, and it doesn't contain any clotting factors or platelets. So it will last in the fridge for up to 42 days, so it's quite useful to have it, you can buy this from the Pet Blood Bank. And we use it to treat anaemia, and particularly anaemic patients who are normovolemic or hypovolemic.

So this doesn't contain plasma or serum, whereas your whole blood does. So if your patient is normovolemic, you can quite easily over. Over transfuse a patient with whole blood, whereas you packed red blood cells, you're more safe because it doesn't contain any of the plasma, it's just the red blood cells itself.

So this is the drug of choice for IMHA. And we do also have package of blood cells available now for CA. Most of your specialist hospitals, your referral centres will have these in store.

We have them in at Northwest, and I know a lot of vets now clinics have them in. Now the vets now have a service where you can borrow, . You can borrow some of their blood products as long as you just buy them one back.

So that's quite useful if you have something out of hours and you have the facilities to get this blood into the patient at your own practise, then you can call up your local vets now clinic and one of those clinics locally usually acts as a hub and will have a batch of blood that you can borrow. OK, so it's important that we do transfuse these patients. If we are transfusing them, we need to blood type them, blood type them early so that if the patient does deteriorate, we can, we know exactly what type it is and we can get a transfusion on board.

Now. It does say here that packed blood cells should be ideally within 7, less than 7 to 10 days old, and that's because the consensus statement states that they tend to have a better outcome if it's less than 7 to 10 days old, so anything older than this just carries a poorer prognosis. Now, negative blood is a universal donor, so any patient, as long as it hasn't had a previous transfusion or it hasn't had a litter of puppies, can receive negative blood.

But we are starting to see a shortage of negative blood for this reason, so we should be blood typing these patients and giving them the appropriate blood. Now blood blood typing kits are really cheap, really quick. It, I think it takes about 30 seconds to do the, the one that's pictured on the right.

So they are really easy and if you are a practise that's set up to be doing blood transfusions, then you should also have these in practise as well. Now dogs don't have naturally occurring aloe antibodies like cats and humans do, so that's why they're generally safe to have negative blood regardless of their blood type. But again, you just need to be careful and we do need to, we should ideally be typing these patients.

So we can also do a cross matching kit. So this is gold standard, so you can blood type or cross match easily, but if severe agglutination is present, it's not always that easy. So you could do the cross matching kit, and if it's really severely agglutinating, then it might just auto agglutinate any blood that comes into contact with, whether it be the correct type.

The wrong type. So in this case, it is a little bit more difficult. I would still say to do it because it might not happen.

It doesn't happen with all IMHA cases. We always cross match all of our IMHA patients. So it's only when it's really, really severe that you just need to bear that in mind.

And we have had a patient in the past where every single type of blood that we cross matched with came up positive for a reaction, and in that case we had to phone the pet blood bank and say all of our blood is. Not usable for this patient, what would you recommend and then they can start doing cross matches for you there. But that's quite rare that this will happen.

So you can see the top image. The middle tube is the example tube. And sorry, that's the patient's tube.

So the, the two on the left and the right are the example tube. So the one on the left is positive for a reaction, the one on the right with the blood at the bottom is negative for a reaction. So this is our patient's blood in the middle, so you can see that it matches the negative.

So this just means that this patient, if it receives this blood, it's not likely to react. So it's safe to go ahead. If it looked like the one on the right, that's a positive cross match, so it's positive that it's likely to have a reaction if you were to transfuse this blood.

So that's a way of interpreting these. So it is really easy. The kit is at the bottom, so you come out with about 7 tubes to start with.

It's, you have to closely follow the instructions, but it is really easy to follow. So I would recommend getting these in-house as well. And usually when you are transfusing pachre blood cells, it's, we say 1 mL of Pachre blood cells increases the patient's PCV by 1%.

So 1 mL of Pachre blood cells per kilo will go up by 1%, so that's quite an easy sum to remember. So for administration, we need to make sure these, this blood is kept in the fridge, so just bring it out, you can either warm it in lukewarm water. Don't put it in warm water, it just must be lukewarmed tough, because if you do overheat, it can cause the cells to become damaged and also agglutinate inside the bag, which we definitely don't want.

So the, the easiest thing and the safest thing is just get it out of the bag, leave it on the sides, maybe put it in your hands, just roll it between your hands and just let it warm up naturally if you have time. Now these bags are really delicate, so if you drop this bag, it is likely to burst, whereas it's they're not as tough as if you were to drop a normal fluid bag. So we do need to be a little bit more careful with these.

And we should be using a blood philtre just to make sure that we're catching any blood clots that might be in the line that might have developed. And the blood should be kept at room temperature for less than 6 hours, and this is just to prevent the growth of bacteria. So this is much more likely to grow bacteria than the likes of a fluid bag, and that's because it contains much more.

So it might contain any bits of glucose or anything from that might be relevant in the bloodstream normally in these patients. So therefore it's more likely to carry bacteria or to let bacteria grow. So that's the reason that the transfusion should be given over 6 hours as a maximum.

So Hartmann's solution shouldn't be administered alongside any blood product, and that's because it does contain some calcium. So the citrate that's inside the blood transfusion, the blood bag, just stops it from clotting, but the citrate will react with the calcium that's in Hartmans and can cause cause it to collate and cause little micro clots. So we do need to be careful with Hartman's solution and maybe swap it out for saline while the patient's receiving the transfusion, or maybe they don't need another fluid at all, maybe they're allmovolemic and they can just receive the packet of blood cells.

So when we're monitoring these patients, usually if a reaction is going to occur, it'll be within the 1st 15 minutes, so we need to monitor them closer in that time, but it can still happen after that. We usually take a baseline TPR so that we know exactly what we're dealing with, and then the TPR should be performed every 5 minutes for that 1st 15 minutes just because of the higher chance of a transfusion reaction. And then monitor every 15 minutes for an hour, and then every hour for the duration of the transfusion, which is usually over around 4 hours.

So transfusion reactions, there's two different types, so they can be immunological or non-immunological, and the immunological are caused by antibody reaction against the recipient's red blood cells. So this is the patient's immune system starting to attack this new blood. And it might just start to completely agglutinate, and you might see pictures like this, so this is urine on the right, so the body is literally just rejecting this blood and it's, it's getting rid of it, it's destroying it.

So it might have an acute onset and it will result in the destruction of that transfused blood. And it can also have an anaphylactic reaction as well. If this is the case, then we should be given antihistamines for these these patients and our patients are likely to go onto steroids anyway, so that will also help.

Now an immunological reaction, you might see tachycardia, tachypnea, pyrexia, facial swelling or I've seen itching. Vomiting, we might see some cardiac arrhythmias, they could start a seizure or twist and you might start to see some hemolysis if the patient is just hemolyzing all of this transfusion. So it's usually an acute onset and quite often I've seen nurses and myself included when I haven't administered many blood transfusions.

Look at the baseline TPR and then we're going in every 5 minutes. If the tachycardia worsens slightly or the tachypnea does or maybe the the temperature changes slightly. I would, well, it's quite common that the nurse will think, oh, a reaction is occurring.

Now if this is a true reaction, that tachycardia and tachypnea will be marked, so it will be really high. So quite often a patient's heart rate will go up to the 200s, maybe even more in a cat, and the pyrexia will also be quite marked. So we need to bear in mind that we are going into this patient's kennel every 5 minutes.

We're interfering with them, that we're doing a TPR so it's likely to fluctuate. But we need to just bear in mind that it's likely to be quite marked if it is a true reaction. If you are worried at all, stop the transfusion and just contact the vet.

It's always better to be safe, and in non-immunological, this is usually caused by incorrect handling or storage of the product. So usually we say keep these, keep the bags of blood in the fridge. Ideally in a separate blood fridge rather than one that we're opening all the time, say for our vaccinations, and that's because these are living red blood cells.

So we need to be careful, make sure that we're maintaining that stable temperature and also they require oxygen. So we should, they recommend that you should be mixing the blood gently. Every couple of days, and that's just to make sure the blood cells that are on the outside are receiving the oxygen, but as you mix it, it's just making sure that the red blood cells that are in the centre are also being exposed to that oxygen on the outside of the bag to make sure that they can carry on living and provide them with that much needed oxygen so that they're healthy cells that we can transfuse to our patients.

So all of these could damage our blood. And it could also be due to the administration of a stored product if our patient has liver failure. So ammonia can build in red blood cells when they're being stored, and this is this is dangerous for a patient with liver disease because they can't always convert that ammonia into urea, so the ammonia can start to build and they can't get rid of him.

So that can be quite dangerous. Or it could also be maybe we have a volume of overload. So if our patient is normovolemic and we're administering a blood product, and we're also maybe giving fluids alongside, we need to just be aware that we're checking this patient's hydration status and vascular status.

So is our patient actually hypovolemic or dehydrated, and if so, we need to make sure that we're providing the fluid in the blood accordingly to this patient. So supportive care, so dehydration will need fluid therapy to correct and don't be afraid to use appropriate if we are monitoring for dehydration, but also be aware that overhydration can occur if you're given a blood product. Give oxygen therapy, so these patients have that decreased oxygen carrying capacity, so give them oxygen, especially on triage while they have that low PCV.

You can give antacids to the hospitalised patient, and this is just because of the high dose of steroids that they're receiving. Quite often they'll be on an antacid in the hospital, but we don't deem it necessary to send them home for ongoing treatment with antacid. And it's important to get these patients eating, so enter a site.

It's important that we maintain our enterocyte health in our gut. And early nutrition has been proven to give a better outcome for many different conditions, so this is a biggie. And make sure we have good hygiene just because our patients are immunocompromised, so they are a higher risk being in the hospital in general.

So just barrier nurse these patients as and where you can. And we need to monitor our patient's cardiovascular parameters very closely, monitor their demeanour, monitor for any signs of gastrointestinal haemorrhage, so do we have any melena, do we have any fresh blood coming out? And monitor for any evidence of coagulopathy.

So do we have any petiation starting? Do we have any signs of excessive bruising if we're placing an IV or doing an injection as a hematoma care? So once you have one immune-mediated.

Condition, it can be quite easy for the immune system to stop being affected in other ways. You can get other things like immune-mediated thrombocytopenia or immune-mediated polyarthritis. So maybe your patient starts to become lame.

So do look out for these other signs and monitor the PCV every 12 to 24 hours and also do your total protein and just monitor your saline agglutination so you can repeat. Things like your saline agglutination, so as your patient is on treatment, the saline agglutination should start to become negative or should start to appear less. It should start to agglutinate less.

Also look at your smear, if it's regenerating, and you can also repeat your Cooms test if necessary. OK, so prognosis, so the mortality rate of this condition is quite big, so 25 to 70%, and the relapse rate is 11 to 15%. And as I mentioned earlier, if we do see a patient relapse.

Quite often it's because they've been weaned off the steroids too early, so it's important that we are maintaining 6 months' worth of treatments for these patients. And usually the cause of death is not from the IMHA but quite often it's from thromboembolism, or maybe the patient's been tipped into DIC or got sepsis. So it can be another, another systemic condition that can be caused secondary to the IMHA and that's usually what the cause of death is rather than this primary condition.

OK, so that's all from me for this evening. I hope you've enjoyed it and I'm happy to answer any questions. Sophie, that was absolutely fabulous.

I did promise them a great webinar and you didn't turn me into a liar. So thank you so much for that. Oh, thank you.

Just a reminder folks that Sophie's other webinar that she did two weeks ago on blood transfusion medicine is available on our website and If you enjoyed this one, you will enjoy that one. And I have no doubt gained huge amounts of information and knowledge from that. So, a big thank you again, Sophie, for your time and your effort tonight.