All right, thank you very much for that introduction. So, hi everybody, I'm Katie, and this evening we're going to be discussing immune-mediated disease. Oh.
There we are. So this evening, the learning objectives that I'd like to get started with, is we will have a refresher about the immune system and what it does and how it works. We'll discuss a couple of the most common immune-mediated diseases.
So this evening I want to just run through IMHA, so that's our hemolytic anaemia, and the treatment that patients will receive for this. We'll run through some IMTP as well, so our thrombocytic patients and their treatment. And to top off at the end, we'll just go through a couple of case studies.
So what is the immune system? So we all know that the immune system is there to stop us from getting diseases and keeping us healthy so that we can live our normal day to day lives. It's made up of a number of different cells and tissues, and together they work to look for invading pathogens.
And a pathogen that they look for is anything that they recognise as being foreign to the body or not self. So, that's how they differentiate between their own, their own body's tissues and anything foreign. The immune system also recognises dead or faulty cells that are self and clears these away too.
So leukocytes are found in our vessels and they are mainly in our blood vessels in our blood circulation and our lymphatic system. And when they encounter any pathogens, they multiply a number and send out signals of alert really to other cells to attract them to the same area. And we do know that some organs have stores of white blood cells, and I think the two that we most commonly would think and associate with our white blood cells would be our spleen and our bone marrow.
But it's worth noting as well that the thymus and also the lymph nodes have stores of white blood cells too. So we've got different types of phagocytes and the most common type is our neutrophil and their most important job is attacking bacteria. Our monocytes are our largest phagocytes, and they play many different roles.
And our macrophages are there to patrol for pathogens and then remove any dead cells that they come across. Mast cells have, again, many different jobs, but they're most known for healing wounds and defending against invading pathogens. So our lymphocytes are made inside the bone marrow, and the bone marrow can be found inside the long bones.
So if you cut through, so the femur, or any other long bone, sort of, and in the central medulla of that bone, it's like a squidgy texture tissue, and that's where you find your stores of your lymphocytes. And some of these lymphocytes, once they have been made in the bone marrow, will then stay around the bone marrow. And these are what we know as B cells or B lymphocytes.
Some of the other lymphocytes made in the bone marrow will go off and they'll stay in the thymus, and these are known as our T cells or our T lymphocytes. So that's quite easy to remember. Our B cells, B lymphocytes are known to produce antibodies and they're alerting the T cells when they come across any pathogens.
And then the T cells come along and destroy those compromised cells and then alert other cells to the area as well. So how does a white blood cell know that something is foreign to them? How does it recognise it against its own body or its own cells?
So it detects proteins on the surface of cells, and every cell of the body has its own sort of different complicated mechanisms of proteins on their surfaces. And an antigen is any substance that initiates that immune response, and that might be commonly one of our pathogens, so that might be a bacteria, a fungus. It could be a virus, a foreign body or a toxin, or a parasite, but occasionally one of our own cells may also initiate a response.
And in that case, that, that own cell will also be known as an antigen. So immunity is great, and we all, we all need it, but it obviously can go wrong. And there are 3 main ways that you'll find immunity problems occurring.
The first of these is an immunodeficiency, so that's sort of a lack in the ability of the immune system to perform normally. And that can be for many different reasons. And in a human medicine, scenario in the third world country, this is definitely caused mainly by the malnutrition.
But we are more likely to see it in old, older age. So our geriatric patients, our neonate patients as well. There are inherited conditions that can cause somebody to have a lack of immunity, have an immunodeficiency, and some medications as well can also cause that immune system to be suppressed.
So, not only do we have drugs that will do that on purpose, but we have our chemotherapy drugs, and they'll also leave people open, to To, to disease and, and pathogens, and the same goes for our veterinary patients. The second type of problem that we can get with our immunity is hypersensitivity. And this is basically an overreaction of the immune system.
So, for example, if we are stung by a bee, so if a patient has a bee sting, normally in a normal patient, that immune response will happen and it will happen in a localised area and there might be some swelling and itching, but that might go down. But in some people and in some animals that might cause an anaphylactic shock. And in that sort of state, the immune system is in overdrive and in the end it does end up damaging healthy tissue as well.
So that is classified as, as a hypersensitivity reaction. So that's another immunity issue. And then the 3rd and the one that we're really gonna focus on this evening is an autoimmune disorder.
And this is when the immune system will mistake healthy cells of the body as being dead or as being faulty. And this is what happens in conditions such as immune-mediated hemolytic anaemia, immune-mediated thrombocytopenia, and immune-mediated. Polyarthritis.
Sorry, I forgot what I was saying then. And so that's when, our, our body cells are, are just working really normally, but then they become antigens because the, the immune system gets confused, essentially, and starts attacking those healthy cells. So different types of immunemediated disorder.
The list is not exhaustive that I'm going to go through this evening. But just to give you an idea of what might happen, it's it's quite common that we might see something happen that's been initiated by an immune mediated illness. And the most common that we'll talk about this evening is our hemolytic anaemia.
We also will see thrombocytopenia. Many different types of skin disorders can also be started off by an immunity, autoimmune disorder. We have immune-mediated necrotizing myopathy, so that's with the immune system starts to attack muscle cells, and so muscle cells might die off in that condition.
Immune mediated polyarthritis, which we'll have a case study about later. I mean, complex glomerulonephritis, so that is a renal condition. And also neurological disorders as well.
So the first one that we're gonna just go through this evening is immune-mediated hemolytic anaemia, which I'll refer to from now on as IMHA. And this is our most common immune-mediated disorder in veterinary patients. We see it much more commonly in dogs than we do in cats, although we do see it very commonly in our hospital in cats.
And it's known to have a very high rate of morbidity and mortality. And, by high rate, we're thinking sort of 50% and over really. It has also got quite a high relapse percentage as well.
And patients with IMHA often will have a concurrent thrombocytopenia. And so in that situation, we'd call that an Evans syndrome, and that is quite common. And if they do have this Evans syndrome, then it might be that they become coagulopathic, so they're not able to clot properly.
And complications are very, very common in, in all immune mediated disease, but particularly in these blood disorders, we see a lot of thromboembolic events like, we have, PTE, so we'll have an embolus released into the lungs, and this can be the cause of death in many of the patients that we have in the hospital. So what is IMHA? So this is when the immune system attacks its own red blood cells.
So the red blood cell is really what we focus on in this disorder. And the cells are humanised, which means they're destroyed, causing then there to be an anaemia because we have a lack of red blood cells. And often in the hospital, they will present to be quite lethargic.
They might be anorexic or a little bit of their food. They tend to be already pale or jaundiced when they arrive to us, and they might have a pyrexia. And then they also will quite likely already have a change in their respiratory rate or their Respiratory effort by the time the owners noticed, because this disease is quite silent, and it's only when it gets quite progressed and the patient becomes anaemic, that then the owner will notice these signs.
So, as I said, yes, they will, they will present to us often quite Kipnik and definitely pale or jaundiced. And IMHA is basically diagnosed once we've excluded all else. So it's really important that when these patients come into us, that we take a very, very thorough history from those owners just so that we can try and rule out any underlying disorders.
So the normal lifespan of a red blood cell is between 100 to 120 days, and IMHA will target all age of red blood cells, so it doesn't really discriminate, so it will just attack whatever is there. We have a number of different anti red blood cell antibodies, and the most common ones that we see are our IGG, our IGM and our IGA and these attached to components of the red blood cell membranes. This causes extra vascular hemolysis, which as it says, it's outside of the vessel.
But in severe reactions, these antibodies can attach to the membrane of the red blood cell, which will cause an influx of extracellular fluid into the cell, causing it to rupture or hemoly. And this could happen inside the circulation. And when it happens inside the circulation, it's referred to as intravascular hemolysis.
So when we have intravascular hemolysis, the haemoglobin that's released from that red blood cell and sort of rupturing, basically, is released inside that bloodstream. And then once we see from that, we would notice in our patients that they would have a haemoglobin anaemia, and also a hemoglobinuria. So they'll have a pigment in their urine and also in their plasma.
And this doesn't occur with our extravascular hemolysis, because the red blood cells removed from the vessels by something called a mononuclear phagocyte system. So that's not something we're going to go into today, but it basically means that the red blood cell has already been pulled into the bilirubin metabolic pathway. So what On that cell has ruptured or hemolyzed, the bilirubin and the haemoglobin that has been released there is is discarded as waste as normal.
So we don't see it in a build up and our patients with extravascular hemolysis won't show us our hemoglobinenemias and haemoglobin urea. So IMHA can be diagnosed as being a primary or a secondary condition. And if we're diagnosing primary IMHA, an idiopathic condition, that just means that there's no other cause found of this hemolytic anaemia.
It means that autoantibodies have been produced against that animal's own red blood cell membranes. And normally our T lymphocytes stop this from happening. But in these animals, it might be that they actually have an impaired function of T cells.
And it's really interesting. There's been a couple of studies now that have shown in rats, and mice that actually impaired thrombus, sorry, T cell function might be genetically related, and she Showing some, some sort of genetic disposition, which might go somewhere and explaining in our canine patients, especially that we will normally see this. We can see it in any breed of dog, but we tend to see a lot of it in spaniels, and definitely female American cocker spaniels, are predominantly the, the breed of dog that has it more than others.
So a secondary IMHA is when we have this immune response to a foreign antigen, that are associated with that red blood cell membrane. And that just means that we have diagnosed an underlying process that has then secondary caused this IMHA disorder. And that can be, as we discussed earlier, something that's bacterial.
It could be a parasite, there could be a neoplasia there. And it has been shown as well that in recent vaccination, maybe within 30 days of vaccination, some patients are developing IMHA, but it hasn't been shown that it's a particular type of vaccine or that it's a particular brand or anything like that. So, we obviously still vaccinate as routine for our patients, but it might be worth thinking about, repeat vaccinations in patients that have already previously had an immune condition, because it might be that that was associated in some way.
So once we have a patient in the hospital, and our vet is thinking that it, it probably is IMHA, there's a number of different things that we do to investigate. So, as I said earlier, the first thing, and the primarily what we want to be doing is taking a really thorough history from, from that owner, so that we can pick up on any signs that there might be something else, else. And then moving on to do a, a really good physical exam.
And just checking that this patient is not jaundice or pale. They might have splenomegaly, so just meaning that they have an enlarged spleen. They might have a hepatomegaly, so having an enlarged liver.
They might already be showing that they've got a pigment your ear for different pigment in their urine, and they might have a pyrexia and a lymphadenopathy as well. Often these patients, as I said, will already be presenting to us quite anaemic. So it's quite common that they would present with a tachycardia, and they may even have a gallop rhythm, and this is seen probably more commonly in our cats.
And they might also present to us with a heart murmur. If we think that this, patient has got a heart murmur and their PCV is under 15 when we see them, it might just be that that heart murmur is a hemic murmur and that, that is caused by that, that low Pa cell volume. So theoretically, once we've corrected the anaemia, the heart murmur should go away.
We'll do an in-house PCV and total solids, and normally with an IMHA patient, we'll see them with a low PCV. So normally under 25% in the hospital. We'll do some smears and have a look for cytology and look for our immature red blood cells.
We'll look for any signs of regeneration, look for nucleated red blood cells, and also any signs of auto agglutination. And then, often our clinicians will request a Coombs test, sorry, which will, look for positive results from a direct anti-globulin. And a very simple test that we can do with our patients in-house is an in-house in saline, a glutination test.
And we can just perform this by mixing one drop of saline on a slide with one drop of that patient's threshold blood, and just swir it around a little bit on the slide and just see if there are any changes to those red blood cells. Sometimes it can be quite obvious to the naked eye that there is a glutination. So just like on this slide here, you can see that those cells are all agglutinating there, it's all clumping together.
And if we can see it with the naked eye, we'd refer to it as being a major positive. But sometimes we'll then have to just look at it under the microscope if we're not seeing anything, obviously, and just check because there might be an autoglutination that we can see under the microscope and we'd call that a minor positive. We'd obviously send off a complete blood count to our lab.
And send off a biochemistry as well. We want to be checking for underlying diseases. We want to have a look at this patient's clotting times, check they're not coagulopathic.
We might be worried that they might have DIC, so our, disseminated intravascular coagulopathy. So when we have lots of little clots everywhere in the body. And we want to just check on our biochemistry that our liver enzymes are OK because we might see some thromboembolisms or ischemia in our liver from this disease process.
But also we might have an increased enzyme secondary to hypoxemia from this anaemia as well. So then the next step would be that these patients receive some imaging. We want to really be fully investigating this patient and it's quite a challenge just to make sure that there isn't anything else underlying before we go ahead and, and definitely diagnose this patient as having a primary IMHA.
And, often when these patients present to us at the hospital, we'll do a, a point of care scan. So just take our bedside ultrasound monitor and just have a quick look for anything really glaringly obvious in their chest or in their abdomen. But then they will probably go off as well and have a proper ultrasound scan, with a specialist and they might, might well have a CT or an MRI depending on the presentation of the case.
We'd also have a quick look to see if there's any pulmonary thromboembolist or PTE because that is a very common complication of this disorder. And we'll check as well with our ultrasound, just to check the spleen and the liver sizes and just to see that they're OK, that there might, might not be any signs of neoplasia or anything like that. If a patient has presented to us with a murmur and we, we think that it might be hemic, sometimes our clinicians will want to do an echocardiogram just to see if we can detect any underlying heart disease or whether this is just a hemic murmur that we're hearing.
And some other causes that can sort of happen with our IMHA and our ITP and sort of all of them, can actually be pregnancy or recent abortions or birth. It is uncommon, but it, it, it can also kick off our immune system to have this response. Some of our IMHA patients will go off and have a bone marrow aspirate, and here we'll look for non, not see if our anaemia is regenerative or non-regenerative.
And sometimes we might have hyperplasia of our bone marrow with IMHA, but it will really just tell us how well that patient is regenerating their cells, to see how quickly they might recover from this problem. So then the treatment for our IMHA patients. So, any immune-mediated disorder is treated in a fairly similar way.
So the idea is that the immune system is attacking and so what we want to do is suppress that immune system. And the first line of defence really against our immune system would be to start administering glucocorticoids. And it's recommended currently that prednisolone is used as a dose of 2 to 3 or 2 to 4 milligramme per kg per day as a starting dose.
But as this dose is super high, we will often see a lot of side effects with our patients. And also the side effects might start on much, much earlier in the treatment course as well. So to combat this, some of our clinicians will use conjunctive therapy with other immunosuppressants, such as azathioprine or cyclosporinene.
Cyclophosphamide did used to be recommended, but, currently is not due to a study, just indicating that there might be a poorer outcome in patients with, with that type of combination. So if a patient is on prednisolone and cyclophosphamide, they might not do so well, as the patients that would be on maybe azathioprine or mycophenolate. And these doses are very, very high, so the idea is that over time, we can taper these doses off.
And in order to do that, we need to be doing regular haematology testing to check the response to the therapy and to check any changes when we're starting to reduce those doses. Some patients, requiring IMHA treatment might not respond to the drugs as quickly as others. And in this case, in certainly in our hospital, they might be a candidate for plasmaheesis, which we'll speak about in a moment.
And then also this being an anaemic condition, a lot of these patients when they come to us, will require some sort of blood therapy. So having blood products to get them over sort of this critical period whilst all of this immunosuppression is taking place and their body can start to regenerate their own cells. So as I said, the glucocorticoid of choice, in our immune mediated conditions is prednisolone.
And it normally takes about 5 days for signs to improve. The way that our glucocorticoids will work is by slowing the immune response and therefore the rate at which those RBCs are destroyed. And the same goes for in other immune conditions such as ITP.
So in ITP what it would do is slow the rates at which the platelets are being destroyed. But unfortunately, we see pronounced side effects from our prednisolone and I'm sure you're all aware that the main ones that we tend to see are our PUPD so are drinking a lot more, are urinating a lot more. We'll see them really, really hungry.
They're asking for food all the time. We'll also see muscle mass loss and thinning of their, their coat. They might look a little bit scraggly.
They might show signs of panting and having an altered mentation. So maybe behaving slightly sort of abnormally for them. And also a hypercoagulability as well.
So that's something that we really want to watch out for. And we'll try to taper this dose over sort of 4 to 9 months at regular sort of intervals as well, along with those bloods. So if our patients are showing signs of side effects from our prednisolone quite early on or if those side effects seem to be quite severe, then we would normally, our clinicians will start them on an adjunctive immunosuppressant therapy.
And one of the ones that will go for. Initially would be azathioprine, and this is edoema, so a disease modifying anti-rheumatic drug, which is given once a day. And the way that this works is by reducing the immune system and by limiting or preventing tissue damage that's occurring.
We again will use this very long term and we'll use it alongside the prednisolone literally until the end of those courses. So it, they'll stay, even though the prednisolone doses might be being tapered and tapered and tapered, the dose of the azathioprine won't change, and then we'll just stop it at the end with that prednisolone. Cyclosporin will work by reducing function of the lymphocyte.
And the dose really depends on how the drug has been reconstituted. It's available in many different types and many different strengths. So depending on how we're, we're choosing to give it, depends on, on the dose that the clinician will choose.
So another therapy that our patients with immune-mediated blood disorders will start on is often anticoagulation therapy. And we will use, sort of a mixture in our hospital of heparin or aspirin or maybe clopidogrel, and use these in our patients, both intravenously and also orally depending on the stage of treatment in that patient. As I said earlier, pulmonary thromboembolisms are really high risk complications for these patients.
And it's very, very common that we'll see a patient maybe several days into their treatment, and they, they might sort of develop this sudden tachypnea, this sudden sort of increased respiratory rate. And if there is no other reason that we can really think about with those patients, then, then we often just assume actually it is a PTE because they are that common. Some studies have suggested that possibly an oral anticoagulant therapy is better than an injection, but that's kind of up in the air, so it really is just, at the discretion of, of the surgeon.
And it's shown that dogs that are showing a hypercoagulability with these diseases have a much higher rate of, morbidity and mortality, unfortunately, due to the risk of them going into DIC. So another treatment choice that we do have available to us with our IMHA patients is a splenectomy. It tends to be the last resort, but it has been shown that it could improve patients with IMHA when they're not responding to medicinal therapy.
Because of the nature of the disease, it's an extremely risky thing to start cutting open a dog that's a, anaemic and, and B, might have some underlying thrombocytopenia as well. And also, these patients can be very, very sick, and it's likely that maybe these are the sickest patients if they're not responding to the, to the medicines. So, for that reason, it's sort of questioning really whether it's that ethical to do it on a patient that's sick.
So it really isn't done very often at all. So a little bit blood therapy. So, often these patients are very anaemic, so we want to treat them with our blood products and to try and make them just feel a little bit better in the hospital while those treatments start to take, take action really.
Normally patients have been dealing with this problem for some time, maybe some weeks, and possibly months before they've become anaemic enough to present to the hospital. And so you'll find that these patients might present to you with a PCV that is quite startling, so maybe a 10%, and actually they're coping really, really well, and it's just because their body is coping with that chronic drop in PCV. But sometimes they will decompensate and require these blood products just to get them through this early treatment phase.
And the things that we'll look out for in our hospitalised patients to see if they are sort of needing this blood transfusion will be that they are developing a tachycardia. They might be tachypnick, they might have very pale mucous membranes, a lethargy, if you've got a new type of anorexia, or if they do have a sudden drop in PCV whilst they're with us. So we'll tend to give them packed red blood cells to try and elevate their PCV.
And at our hospital, we would always blood type every patient and that really is gold standard. And cats 100% of the time need to be typed so that they receive the correct blood type for them because they're at much higher risk of having much more serious blood transfusion reactions. In an emergency situation, if a dog does present to your hospital, and we're presuming that they are IMHA or that they have another anaemia, and they do require packed red blood cells, but you don't have the facilities to blood type them, it is safe for a dog that has never had a blood transfusion before to receive one unit of the other blood type.
But it isn't gold standard, and there is, more of a risk that the next time that patient receives blood, whether it be their type or not, that they might have, might, they might have a reaction as well. So once we've made the decision, the patients receiving blood, it's worth noting that the blood products themselves can cause problems of their own. So this isn't a benign procedure and the monitoring of these patients needs to be really, really top.
So we need to start thinking about monitoring these patients really closely once we start the blood transfusions. We want to take a baseline TPR and check their capillary refill time and their capillary, their mucous membrane colour and make a note of that as well. And also just check that either the IV that they have in place already is very, very clean and you are happy to give a blood product through that, or if we're not happy and we're concerned about an IV, then just placing a new IV specifically for the blood transfusion.
We want to be flushing those catheters with saline 0.9%, because anything that is sort of Hartman's or, or ringers, compound sodium lactate. So if this patient has had fluids, for example, going into the IV, that can react with our blood products.
So we want to make sure that we're really flushing them very, very well before we start the product off. And initially, we want to start the blood products slowly so that we can really closely just check that they're not gonna have a very acute reaction to it. And normally in our hospital, we'll start these patients on 0.5 to 1 mL per kg per hour for the 1st 15 to 30 minutes.
And then if they are coping with that transfusion, they're tolerating. It really well, then we'll increase that rate to give a total volume in 4 to 6 hours. So, all of our blood products, once they're out of the the fridge or the freezer, they need to be used within 6 hours, because that's when they're going to expire.
That's when they're not safe to give any more. So we want to be giving it in under 6 hours, but depending on the patient, we might want to slow that down. And for our cats, if we do give our blood products and they do have an underlying heart condition, or we're worried about overload in these patients, we would maybe divide the blood transfusion up into syringes and then refrigerate the syringes that we're not using at the time in order to give it a longer lifespan, really, so that we can then give each syringe over sort of 4 to 6 hours rather than the whole transfusion.
And that works quite nicely for some of our feline patients, especially. So if we're gonna be doing any type of transfusion, we want to make sure that our monitoring is very clear and concise, and by having a special monitoring sheet, we can do that really well. The types of things that we want to include on our sheets are the blood type of the animal, but also the blood type of the product that we're going to be giving to them as well.
Having the patient's weight on there because that's going to help us work out, a running rate for our blood product. Any notes if they've had a crossmatch or if they've not had a cross match or are there any notes relating to that, then we'd also put this down on the sheet. Any of the product details.
So we'll tend to put in the expiry date of our blood and the donor number. They will have their, different, ID codes as well. And this is really for, monitoring any reactions in the future.
So, It is quite possible that even if a patient doesn't have an acute reaction to a transfusion, they might have a delayed reaction later on. And so it's really good to just have a look back at these transfusion sheets to see which units these patients were given, if the bag has been thrown away, for example. We also have a space on our sheets here for the vet's transfusion plan, and this is completely essential because obviously by giving a blood product, that is a prescription medicine.
So we, we want to definitely have clear instructions if they want us to do it at a particular rate or over a particular time period, then that's all something that they need to write on the sheet for us. We'll have a note section as well just to write down if there are any problems occurring, whether that be problems with the transfusion itself or whether that be any problems with the monitoring of the transfusion as well, or if we're suspecting any reactions at all. And initially, as I said earlier, we want to be TPRing these patients every quarter of an hour to half an hour until we know that they're, they're tolerating it very, very well.
And so normally, if a patient's transfusion is going super well from the start, after about maybe an hour or an hour and a half, we'll start to just TPR them out and just note those down on the sheets. Monitoring the temperature is very, very important. And if we see a temperature increase of over one degree from our baseline temperature, then we're always instructed to stop that transfusion and contact the clinician so that we can troubleshoot that to see whether we think that this is an acute reaction, whether it's a problem with the blood product.
But also worth noting that actually, In a very anaemic patient, if they have been quite anaemic, it might just be that they're a little bit on the hypothermic side due to a lack of perfusion. So, actually, maybe an increase, to a normal temperature might not show us that they're having a reaction, but it might just be that they're being reperfused and that, that's just a good temperature for them. So just having that though in the back of your mind as well.
So our first case study, which is our IMHA one is little Tikka. She was a beautiful little 9 1/2 year old female neutered crossbreed from Portugal. And she presented to us with ectteric and pale mucous membranes, as you can, see in this photo.
She was very, very yellow. She was very lethargic. She could barely sort of mobilise herself really when she presented to us.
She was extremely titnick and tachycardic as well. She had a PCV of under 10%, I think it was 8 or 9%. And initially, we started her on her immunosuppressant therapy, and she received a lot of pack red blood cells.
But because she, wasn't responding quickly enough, to the, the medications, and her IMHA was so severe that she was just eating through all of the packed red blood cell transfusions we were giving her, our clinicians decided that she would really benefit from having something called therapeutic plasma exchange, so a plasmaheesis. And this is where large molecular weight substances such as antibodies are removed from, from the plasma. And the way that we do this is by using either a special machine designed especially for plasmapheresis, and, and that machine also does dialysis, or by using a machine that we call a cell saver.
And, with her, we did use our cell saver. So I'll go through that with you in a second. So with TPE we want to remove whole blood from our patient and that's done at a calculated rate for them.
The blood is then spun down and the packed red blood cells taken from their spun down blood is given straight back to them. And then we basically use their, their plasma as waste product because that's what's got all of our antibodies in it. And so we replace their, their plasma volume with fresh frozen plasma from donors.
So here we can just show you what we did with Tika. So, here we have syringes prepared with our ACDA, so our anticoagulants, so that we can draw up this blood safely and, and it won't clot. And she had a central catheter placed in her jugular vein that we were able to draw this blood into.
And if we're going to be doing this, then we want to be drawing the blood fairly slowly from the jugular and also rotating that syringe as well the whole time, just so that we're really mixing the ACDA with the blood. And then the next thing we'll do is our saver, which is this lovely machine here. We inject, in a sterile fashion, into a special chamber on this machine, all of that whole blood.
And then that blood is, basically a giant, is in a giant centrifuge. And the machine basically spins the blood into all its separate components, and it washes the cells as well. So it will wash, the cells and it will wash out all of that plasma, and that plasma will go into a waste container.
The packed red blood cells, which we want to keep, stay undamaged by the machine and they're pushed back up into a bag, by which we can then just transfuse them straight away back into that patient. So they're receiving their own blood back. And alongside that she received fresh frozen plasma as well.
So, so we replaced her plasma completely with somebody else's who didn't have those antibodies to attack her cells anymore. So we repeated this for 5 cycles in that one day. So that is literally taking out that set, set volume of blood, spinning that blood down, giving it back to her, waiting 20 minutes, and then doing it again.
And the monitoring for her was very intense. So we wanted to have her on a multi, multi-parameter monitor, monitoring her heart rate and her blood pressure, and her temperature. And she was very, very poorly, so she really didn't do, do too much, really.
She just let us do this whole thing. She was still very, very anaemic when we started doing this. So as well as her own packed red blood cells, she did need more packed red blood cells from the lab.
And after these rounds, she felt so much better. She did have a further cycle of this TPE 2 days later, because, by this stage, she's, her body's producing more antibodies. But after that, she actually picked up really nicely.
She was staying in our ICU. I think she stayed with us maybe 2 to 3 weeks, and she went home, and she's still doing well now. So, she's a really happy ending for us, which is nice.
So then the next condition that we're gonna talk about is our immediate cytopenia. And that's the most, the second most common disease process that we'll see with our patients. So instead of the immune system attacking the red blood cells, as in our hemolytic anaemia, this is when it attacks the platelets in our blood.
And this causes excessive bleeding, which can happen in trauma. But then if the ITP becomes bad enough, we can actually see spontaneous bleeding. So just bleeding for no, no reason at all.
And if this does happen and it's excessive, we can then obviously see an anaemia on top of that. And just to note this image that you can see here on this slide, yes, it is, it looks like pure blood, but actually it is urine from a patient with ITP. So their symptoms can be very, very severe.
So what does the platelet do? So we all know that we need platelets in order to to not bleed. They are little fragments of cells and they do have many, many uses, and they're constantly on the lookout for little holes in the cell, in the vessel walls, sorry, and they'll fill any little gaps that might appear in any vessel walls.
And they'll form a plug if we are cut, if we suffer a trauma, in order to prevent significant blood loss. And then by forming that plug, they then also are providing a surface for our coagulation factors to form a secondary plug, essentially. They're also there to aid in healing tissue.
So ITP is when our immune system attacks and destroys our platelets, and then from that, our function is completely impaired. And patients with ITP often present to us quite late in the disease process, purely because it it is quite silent, until they start to bleed quite profusely. And for that reason, when they come into us, they will often be, already quite anaemic and pre-presenting with an anaemic symptom as well, meaning that they've had some bleeding somewhere and that might be, that they have had, Melina, so if they're, they're, they're bleeding.
Into their gastrointestinal tract, they might have hematuria as that last photo, so just bleeding in their bladder. And they often will come into us with petiki, so little bruises in our mucous membranes, and ecchymosis, so bruising around the body. Other signs that these patients might show on arrival would be hematemesis, so vomiting blood, and also epistaxis, or we're having our nose bleeds.
And then similarly to IMHA, we really want to be excluding other differentials. And also, if they are anaemic, we want to try and work out whether the ITP is primary or whether that is secondary to actually an IMHA so which would be our evidence syndrome. So just having a look to see whether actually it's a primary thrombocytopenia or not.
And initially, we want to be checking our platelet count because that's our most important thing here. And then our coagulation profiles and our clotting times along with all of our other blood type blood conditions to check for any underlying disorder. Much the same as our IMHA patients will be undergoing a lot of imaging.
They might require blood products. We will start them on glu glucocorticoids, just as in our IMHA patients, at relatively the same doses, so our high doses, and they might need conjunctive immunosuppressive therapy for the same reasons as the other patients. And then these patients might also require a platelet transfusion as well.
We will also use Bin Christine in some of these guys. So, I think Christine is an anti-tubular a normally be used in chemotherapy protocols. It works by increasing our platelet release from our megacarriocytes and impairing the phagocytosis.
So it's basically stopping the the rate at which our platelets are being consumed really by the immune system. And when we do use this as therapy, our clinicians give it as a dose, just as a one-off at the beginning of the treatment, a dose of 0.02 make perk IV alongside those other treatments that we talked about earlier.
And it has been shown in studies that it will decrease the hospital stay in patients with ITP, but it won't change the prognosis. So it doesn't make them, have a worse prognosis, but it's not necessarily going to make them have a better one either. And so sometimes, although rarely, we might want to think about using human intravenous immunoglobulin.
And this again is something that we'll just use once with these patients, but it has been shown that it might get patients home slightly more quickly than the patients that don't receive it. And it might give them a greater increase in their platelet count more quickly as well. And in human medicine it's used very, very frequently, but in our veterinary patients, we don't actually have a lot of studies to go by yet.
So spontaneous bleeding is obviously the biggest complication of ITP. It can happen any at any time and anywhere and it can definitely be life-threatening if it happens in, in the brain, for example, or our internal organisms, they might have a very severe epistaxis. And if we have noted thromboembolisms, we'll start our anticoagulant therapy as soon as possible.
They again are are quite commonly likely to get PTEs or thromboembollysis in our lungs. And we want to really regularly check our platelet numbers and our platelet function as well. So for these patients in our ICU, sadly, we are, we do recommend that these patients are not resuscitated if there is a catastrophic bleed, only because, it's very unlikely we're going to get them back from that.
And actually more likely that we're just gonna cause more damage by performing CPR in these patients because they're just going to bleed, bleed more from having that sort of trauma. So, this is our case study. So this is Flo.
Flo's a 9 month, sorry, a 9 year old female neuter springer spaniel. And actually she only presented with two ecchymoses on her abdomen, as you can see in this photo. And the reason for that is because she's my dog, and I'm a paranoid, ECC nurse.
And so as soon as I saw this, I was in panic mode and took her straight, straight into the vets. So on referral, she actually had no platelets whatsoever on her smear, which was very concerning. And imaging showed that it was, that there was nothing underlying.
So we assumed here that she just had a primary ITP and she's a spaniel, as I said, so she might be predisposed to these conditions. We initiated treatment, so she received a dose of incristine and a very high dose of steroids. But within sort of a two-day period, we had to start her on azathioprine because she was having, very, very strong side effects from the prednisolone.
She was very, very panty, already excessively thirsty and urinating a lot. And also maybe she had a bit of a strange mentation as well. So here was just a timeline of her.
She got better very, very quickly, luckily for her, and luckily for me. But you can see that actually within that same day on the 19th of December, from going to just having those tiny two little bruises and a dog that actually was very, very well in herself, she was developing ecchymosis all over her body. It was absolutely everywhere.
Being a typical springer spaniel, she never actually lost her appetite. She ate very well. And within a few days of having the treatment, you can see that her, ecchymosis, had started to, disappear and she wasn't having any more ecchymosis present either.
So she stayed in ICU for about 5 days of treatment, and after those 5 days, she started to have a lot of platelets, appearing on her blood smears. So she went home in time for Christmas. And follow up with her, we reduced her doses of prednisolone by sort of half a dose every 1 to 2 months, and kept her on the azathioprine until the end of therapy.
And alongside that, we did regular haematology and biochemistry checks to check that everything else was ticking along nicely, and regular smears as well to check her platelets. She was off all medications by August, so that was probably about 9 months of therapy in total. And this February, she did have some bloods, just to have a minor lump removal.
And all of her bloods were completely normal. And touch wood, she, hasn't shown any signs of complications after this. So very quickly, I'll just run through our last case study which is Ted.
So Ted actually came into us, he's a 4 month old male entire border terrier, and we diagnosed him with immune-mediated polyarthritis. And this is when the immune system will have an infla inflammatory response inside the joints on synovial fluid. And, as you can imagine, that can cause extreme pain and swelling, and then sort of subsequently to that difficulty walking and difficulty moving about.
Similarly to all other immune diseases, diagnostics, have been undertaken to seek any other underlying cause of the pain. And it does affect a lot of joints. So it tends to affect, definitely all of our, our limbs, our distal limbs.
And, we started off with treating him with prednisolone and, a lot of analgesia. He required, I think, fentanyl and ketamine, as a constant rate infusion initially through his treatment. So what are our nursing considerations for our patients here?
So analgesia, especially in any patients that have got a condition that's going to be sore. So, definitely for our polyarthritis patients, they'll need a lot of analgesia, and possibly for our neurological patients and, and definitely for patients who have an immune-mediated skin condition. We want to be providing them comfortable bedding, and turning them as well.
If these patients are really very sick and they need recumbent care, and we want to be preventing them from developing any other complications whilst they're in hospital. So any ulceration or aletasis. Some of these patients might require oxygen supplementation, and even if this is just in our anaemic patients just to try and make them feel a little bit better until we can get them blood products.
These patients are going to be started on a glucocorticoids, so we're gonna want to provide them with lots of water and also, if possible, provide frequent toilet breaks as well because they're likely to, to definitely have our PUPD. And if we have a recumbent patient on a lot of our glucocorticoids, but they're able to drink and they, and they're on a high rate of fluids, then maybe thinking about placing a urinary catheter as well. We want to just take care with feeding these patients and give them a lot of love as well.
So thank you. I hope that you found it useful. Here is just some further reading, if you're interested in other immune-mediated diseases and a couple of the ones we've spoken about today.
And this is Flow now. So thank you. Well thank you very much, Katie, really, really interesting webinar.
We'll just wait and see if any questions come through. And just to remind those of you who are new to webinar vet, if you'd like to ask a question, just hover over your toolbar, click the Q&A box and send your question through to me so I can read it out to Katie. Katie, how often would you say you perform plasmaphoresis at the RVC?
For IMHA, we perform it very rarely. So I'd probably say maybe once or twice a year for patients with, an immune-mediated hemolytic anaemia. We do do plasmaphoresis for patients with other, disorders, but it's not something that we do commonly.
OK. And what's the outcome usually is it fairly? It really kind of depends on the patient and I guess we probably don't do it often enough to really know how those patients would have done without it.
Definitely fortika, the reason that they decided that they wanted to do the plasmaphesis was because she was not responding to, medical therapy, and she was eating through, like, tonnes of pet red blood cells. I think she had over 15 bags of blood. During her stay with us.
And she definitely wasn't a candidate for having a splenectomy because she was also thrombocytopenic, with her Evans syndrome. So she, really the only thing that we could do for her then was plasmaphoresis, and the owners were very, very invested and they wanted to give it a go. And luckily for her, it was really worth it.
But those dogs that we do do the plasmaphoresis on tend to be the sickest. So, it's not always a good outcome, unfortunately. Yeah, that it is really interesting.
So we have a couple of questions come through. So one from Stephanie, how can you differentiate between primary IMTP and Evans syndrome? Yeah, so we'll want to be checking out.
So obviously, if we have an ITP patient and they do present to us and they're anaemic, we want to be thinking, is that Evans syndrome, and actually they have a primary IMHA. So what we'll do then is we will do our agglutination tests and we'll also send off raccoons tests to the lab, and they'll be able to tell us whether that patient is auto agglutinating their blood, or whether this anaemia is because of the thrombocytopenia. So it's quite clear.
Because you'll see that actually with a thrombocytic sorry, with a thrombocytopenic patient, if they have also got, an anaemia alongside it, it's because they've got significant blood loss, not because their immune system is eating their red blood cells. So you won't see the same red blood cell, differences on our cytology or anything, because the red blood cells should be normal because they're not, they're not getting affected. It's just the platelets.
OK, lovely. And the next question from Alicia says I had a patient with a negative Coombs, which I referred, and they said despite the negative Coombs, it was likely primary IMHA. Do you know how this works and how common this is?
That's really interesting. Now, I don't actually know why that would be. I guess maybe as, as with anything, we can have negative results from negative or false negative or false positive results from any of these tests.
And I'm not sure what they would have done in order to prove. That it was IMHA, but it's possible that they then did further imaging and further blood work to really rule out anything else. And it was possible that that actually was the only then differential that they had left.
But no, I'm not sure why it would come up with a, a false negative. OK, lovely. And the next one, how often do you perform a crossmatch in your clinic?
So, in our clinic, so we tend to stick by the rule that if a patient has received any blood products before, then they get cross-matched. So if they've had any kind of trauma in their past and they've received a pack red blood cell transfusion or if this is a relapsing patient and we know that they've received blood transfusions in the past, then we'll definitely cross match them. And then if we have a patient that's in that has, so say with Tika, so she, when she came into the hospital, she had several transfusions.
And then once that has been sort of 5 days or so, we then started to crossmatch her. And after that, we cross-matched her for every unit that she needed to have because after 5 days, it's quite likely that the body's built up, its own antibodies to having, having this extra blood. So, we stick with that kind of a 5 day rule.
So if a patient has had, a transfusion on the Monday and they've done really well, but then they look like they need a transfusion 5 days later, we would cross-match them then. OK, excellent. That seems to be the end of the questions.
Wait a couple of minutes and see if any more come through. But otherwise, I think it, is it safe to say that this is one of your favourite conditions with you having springer spaniels? Yeah, no, I mean, I was quite cross with her when she did this because I was, yeah, I said, you know, she's an eight year old springer spaniel, and I woke up in the morning to go to work and I saw these tiny ecchymosis and I was like, oh no.
Here we go. You've done it. You've.
And, I actually was texting a few of my friends at work, in a bit of a mild panic, and they were like, No, gosh, she's fine. She's just, you know, she's a springer. She's just knocked herself.
I'm sure she's OK. But I'm really glad I didn't listen to them, basically. Yeah, and she actually had, I didn't actually go into sort of how what we classify as a, a normal platelet count, but she actually had, Like one of the lowest platelet counts that we'd seen in a very, very long time.
She was at super high risk of having, spontaneous bleed at any moment. She was really sick, but she didn't know it. So, yeah, I'm very, very lucky to have her.
Well, she's lucky to have you as an owner as well, I think. Paranoid, paranoid. So no more questions have come through, so I'd just like to say a massive thank you to our listeners for logging in tonight.
And massive thank you to Tails.com and JHP recruitment. And finally, thank you so much to you, Katie, for delivering such a great webinar, and I hope you can enjoy the rest of your evening.
Thank you very much for listening, everyone. Thank you. Thank you.
Bye bye. Bye.
