Hello and welcome to today's lecture. We're going to be talking about platelets and their role in coagulation. So today's learning outcomes, we're gonna go through the physiology of primary and secondary hemostasis and then go through the basic haematology and how this might help us diagnose coagulopathies in practise.

We're going to list primary and secondary coagulation disorders that we see and list the drugs available to us for treatment of these coagulopathies and know when they might be used. We're going to discuss at the end some common nursing considerations for coagulopathic patients in the hospital. So an overview of coagulation, we have this divided into two sections.

We have primary hemostasis, which is there to stop the bleeding and leads to formation of a platelet plug. Secondary hemostasis is where we have our coagulation factors activated, and this leads to the formation of a mature thrombus. These things happen concurrently, and at any point through these pathways, something could disrupt it.

If that happened, we would have some abnormal bleeding. So first off, looking at primary coagulation. Initially, we have the body receiving an injury.

Now this could be something that's accidental, such as a trauma or a surgical incision in a patient that we believe is to be healthy. We then experience vasoconstriction as a result of smooth muscle contraction. Vasoconstriction is gonna help the body decrease the blood flow and therefore the blood loss from that wound.

By having vasoconstriction, we also have an increase in shear stress, which means that the vessel tightens and that increases the pressure within that vessel. When this happens, red blood cells and leukocytes will move towards the middle of that vessel to again avoid that sheer stress, but also to reduce blood loss from the injury. Our platelets will then travel to the site of the injury on the vessel wall, and they're here they'll clump together binding with exposed collagen on that vessel wall and the lining of the vessel.

Our von Willebrand factor will be released, which will help stabilise that platelet plug formation. And our platelets will release ADP, which helps with platelet adhesion, serotonin, which is going to help with vaso constriction, and prostaglandins, which mean more clotting factors will be released. We'll have our platelet plug formed.

So in order to help us visualise this, I've just done a little diagram, as you can see here. So we have the vessel wall in pink and our blood flow flowing from left to right through the vessel. Within the vessel, we've got our red blood cells and our platelets, and with with our increase in sheer stress, our red blood cells will move move towards the middle of the vessel and our platelets will move towards the site of the injury.

We can see here we've got collagen on that vessel wall, and also von Willebrand factor. So our platelets will bind with these, they'll change shape, becoming thinner and more easily able to aggregate to ensure that we can have this platelet plug formed. So when we think about platelet activation, there are 3 proteins that are involved in this.

The first is fibrinogen, which is synthesised in the liver. This is our most dominant ligand, and so it's something that we hear about a lot. It operates really well in low shear conditions, so we'll often see this in big vessel bleeds.

Our fibrinogen will anchor the thrombus to the vessel wall. Von Willebrand factor is synthesised in our Megaarriocytes and sinophils, and it works under all sheer conditions, so it's really useful in arterial bleeds. We'll see a lot more of vonrilipri factor there.

Von Willebrin factor is good at binding platelets to platelets, so working in platelet aggregation. And lastly, fibrinectin is our third ligand, and this is involved in platelet aggregation, although it's actually incompletely understood how this works, and it's likely to involve multiple factors. But the fibrinogen, we know, is a process that increases stability of the platelet platelet interactions and therefore increases the growth and stability of the thrombus.

So now we have to think about the, the factors that come into it when we think about what the platelets need to be in order to form good platelet plugs. So we need to know that we need to have a good number of platelets in order to stop bleeding. We're going to need these platelets to have a good shape.

They need to be able to locate the injuries sufficiently. And they will need to be stable in order to prevent embolism. So now thinking about secondary hemostasis.

So here is where we're gonna have a white thrombus or a platelet plug needing stabilisation. We can think about this in two different ways. We've got our normal coagulation cascade that we see quite frequently, and we've also got the cell base model.

When we think about coagulation, we also hear a lot about clotting factors. So there are 12 clotting factors numbered 1 to 13, which are listed on the right hand side here. So they all do have individual names, but the ones that we hear a lot that are more frequently termed are fibrin, which is 1, thrombin, which is 2.

We've got tissue factor, which is 3, and calcium, which is 4. So looking at the classical coagulation cascade, here we have our intrinsic pathway on the left, and this is what happens when we have a trigger from damage to the vessel wall. All of the factors involved are kept within that bloodstream, and factor 12 will be activated at the site of injury, and then we'll activate 11, 9, and 8.

This will then lead down into the common pathway. On the right hand side here we have our extrinsic pathway. And here we have again a trigger by the injury, and the injured cells will come into contact with the plasma, which will activate factors 3 and 7 and then in turn they'll activate factors 10, 5 and 2.

This will lead into thrombin formation and again into the common pathway. And at the bottom here, our common pathway is where we have gradual factor activation, leading to factor 10. Prothrombinase, which is an enzyme, will convert prothrombin into thrombin, and the thrombin will then convert fibrinogen into fibrin strands, and this will lead us to having that stable fibrin formation at the end.

So now looking at the cell-based model, which is more often referred to kind of in real life scenarios. This is divided into three phases. The first phase is our initiation phase, and this is very similar to that extrinsic pathway we just looked at.

This occurs on cells outside of the vascular walls, so these are our TF bearing cells. They're fibroblasts, mononuclear cells, macrophages, and endothelial cells. And these don't come into contact until that injury happens.

Coagulation factors here are always in constant production of thrombin, but the coagulation steps do not progress or are not initiated because they're separated from the other components by that vessel wall in a healthy animal. We'll then have our amplification stage, and here we'll have small amounts of thrombin initiating the intrinsic system on the platelets, releasing the von Willebrand factor and the activation of factors 58 and 11. The vessel injury releases those platelets and so they come into contact with those TF bearing cells and so they're all surrounded by these pro coagulation factors.

This moves down into phase 3, which is our propagation phase. And this is where we have coagulation factors converting large amounts of prothrombin into thrombin and therefore converting the platelet plug into a stable fibrin clot. And again, here's that diagram that we can see.

So we've got our, our primary hemostasis, which is where our platelets are moving along here and binding with the collagen to create this kind of platelet plug at the top. And here we can see we've got our fibrinogen strands, and they'll cover over those platelets in order to form a more secure plug or thrombus. So now looking at in-house haematology.

So when we're thinking about haematology, we're looking for three things. Our erythrocytes, which are our red blood cells, our leukocytes, which are our white blood cells, and our thrombocytes, which are our platelets. In terms of our white blood cells, we look for our neutrophils.

These are the most common granulocyte that we see. They're produced in the bone marrow. We know that they're phagocytic and that they'll self-destruct, and they're important inflammatory in inflammatory reactions.

Isinophils are a rarer granulocyte, they're again produced in the bone marrow. And these might be seen in allergic reactions due to being involved with phagocytosis of inflammatory agents from our cells. Monocytes are agranulocytes, and these are again involved in the inflammatory response.

Basophils are granulocytes. Again, we might see these in parasitic immune responses and also at sites of infection. So here they'll release Plottogandins, serotonin and histamine to increase that blood flow to the site of damage.

And lymphocytes are a granulocytes. We know that they are B and T cells. Both of these are developed in the bone marrow, but the T cells are then matured in the thymus.

B cells develop into plasma cells, which make antibodies, and the T cells will then be involved in the immune response. So they'll attack viruses, cancer cells, and transplants. So now looking at our red blood cells, most commonly we're going to see erythrocytes.

Now these are our normal shaped and sized blood cells. These are produced in the bone marrow. They carry haemoglobin so that they can bind with oxygen to develop, sorry, to deliver oxygen to the rest of the body.

And they have a nucleus, which is phagocytosed by macrophages, and once they're released into circulation, they live about 120 days. Sphherocytes are a sphere-shaped red blood cell. They're produced like this because they are produced under sheer stress, and so their sphere shape makes them quite fragile.

We'll see these a lot in hemolytic anemias. And lastly, Hinds bodies, which we can see here, just on the red blood cell. These are basically damaged haemoglobin.

And we'll see this in patients that we have suspected to have ingested a toxin, so maybe paracetamol ingestion or onions or sometimes zinc toxicity. So now we're gonna go through just quickly how we look at a blood smear in-house. We're gonna talk about the feathered edge, the monolayer, the body and the base.

So the feathered edge is the end of this smear, and we like to look at this under low magnification. In terms of today's lecture, what's important here at the end of the feathered edge is looking for platelet clumping, and so we can see platelet clumps like this. We might see leukocytes, but they'll be expressively excessively spread, and we could see red blood cells, but it's not really a diagnostic place for red blood cells because they might be flattened.

The important thing to note is that if we are seeing lots of platelet clumps in the feathered edge, that actually our platelet numbers are going to be much higher than we anticipate them to be or expect them to be after looking at the platelets throughout the rest of the smear. In our monolayer, this is our optimal cell for our optimal place for cell examination. This is where we'll do cell counts.

We'll check that a patient may be if they have an anaemia or a polycythemia. And then looking at the body and the base, we're gonna do this on a low power. This is really useful for looking at low numbers of potential abnormalities, so things such as blasts, infectious agents, or any changes to those red blood cells or agglutinates.

On the right here, I've put about in saline agglutination testing, and this is something that we will do in patients that are presenting with an anaemia. To do this, you want to take a blank smear and place a drop of blood and 3 drops of saline and kind of swirl them around together and look for this agglutination, which is just where we have clumping of cells. If you can see this with your naked eye, then this is what we would call a macro agglutination positive.

But sometimes we might need to look at this under the microscope just to see if there's any agglutination that is smaller that we can't see. So step by step, we're gonna look at that feathered edge and check for platelet clamps, large cells, and any infectious agents. You're then going to scan the rest, looking for leukocytes, neutrophils, enophils, and then we're gonna look at platelet numbers.

Are they increased, adequate, or are they low? So when we're counting our platelet counts, we term it per high power field. So that's the per high power field that you're looking at when you're looking down that microscope slide.

A normal amount of platelets to see per high power field in a dog is around 8 to 15 and in cats it's about 10 to 12. Each of these platelets is going to represent 15,000 per microliter. And a normal platelet count for a dog or cat is above 200,000.

It can be up to about 500,000 in a healthy patient. If we have lower than this, then our patient might be at risk of bleeding due to trauma. And if they have lower than 40,000 total, then they are at risk of spontaneous bleeding, which basically just means that they will bleed spontaneously.

So without any sort of trauma at alls, they could just be asleep and experiencing a bleed somewhere. So now just thinking quickly about anaemia, because we're obviously going to worry about anaemia in any patient who's got a coagulopathy. We have on non regenerative or are regenerative.

So in non-regenerative anaemia, this is where our bone marrow isn't producing red blood cells for whatever reason. Here, you'll see a microcytosis, so a small red blood cells. They'll be normocytic and normochromic, so they'll be a normal sort of shape, size and colour.

And there'll be a lack of response in 3 to 5 days if you're looking at these blood cells on a smear in a patient hospitalised over that time frame. We're going to see reticular cytosis of under 1%, and that's again, just because we're not going to see young red blood cells being produced because the bone marrow just isn't doing that. And then opposite to this, we have our regenerative anaemia, which again is seen in blood loss.

So this is kind of the one we're gonna see a lot more in our co coagulopathic patients. We'll see nucleated red blood cells. They might be quite large, and sometimes they're not quite the normal colour of a red blood cell.

And we'll see a lot of reticular cytosis, so over 1%, and this is just gonna be immature red blood cells that have been released slightly too quickly because they're trying to get those numbers up. If we're concerned about a patient with anaemia, we're going to think of those clinical signs. These patients will be tachycardic and tippnick.

They'll have pale mucous membranes, a slow capillary re full time. They might have bounding or poor pulses. They'll be quite weak.

Some of them might look jaundiced, and in cats, sometimes it's reported that they might develop an acute pika. There are many, many causes of anaemia and obviously today we're thinking about those caused by coagulopathies. We can see bleeding from trauma or tumours that might be bleeding, and our non-regenerative anemias tend to be caused by things like bone marrow disorders or renal disease.

In our hemolytic anemias, this is going to be things like IMHA, so immune mediated hemolytic anaemia, or those toxin ingestions that we mentioned earlier. So now looking into our coagulation disorders. These can be split into two categories, so we'll see acquired or congenital.

And when we think about congenital, this also comes into our breed dispositions and which breeds are maybe overrepresented for some of these disorders. We'll then look at primary and secondary coagulation disorders. So our primary disorders are going to be platelet-based, and our secondary disorders will be something to do with the coagulation.

So this might be clotting factors, sort of limited clotting factors for whatever reason. If we have these patients in hospital, we're going to want to do some diagnostic blood work. Remembering with any patient that we are concerned over having some sort of bleeding abnormality, we want to make sure that if we're taking a blood, we're doing this as gently as possible.

And these patients will often have a full CBC and platelet count. We have a lot of ability now to check platelet functions, so we could do the dimers. These are a form of fibrin degradation products, and in 95% of dogs, they've shown that actually by having a negative D-dimer, this excludes the possibility of DIC, which is our disseminated intravascular coagulopathy.

Our platelet function analyzer tests, these detect abnormalities of platelet adhesion under shear stress. So we might see this requested in patients that have a cardiomyopathy or maybe a chronic kidney disease. And then when we think about our clotting, we can think about looking at prothrombin time, our activated thromboplastin time and activated clotting times.

And by running things like this in our hospitals or sending these off, we can often narrow down where in these extrinsic or intrinsic pathways, we have an abnormality happening. We're also able to look at light transmission agratometry, which will assess the way that the platelets aggregate together, and also tags and VCMs. In the presence of factors such as thrombin and fibrin, we can actually see that the the tag sample will be insensitive to platelet function.

Sometimes people will run two tags alongside each other with two different activators, and this will give them more information on clot strength. It's a global coagulation test, and it looks at platelet function and also the clot formation. Patients who are concerned of having any bleeding problems will also have a lot of diagnostic imaging.

Initially, when they present to the hospital, being able to do a point of care ultrasound is probably the first port of call for our clinicians because it's a traumatic. They don't have to have any drugs normally to have this done. And it can really give our clinicians a good sense of what might be going on with the patient.

When they're looking at this patient, they'll look for any gross abnormalities. So they'll be checking for effusions. You know, maybe they'll, there'll be a hemothorax or hemoabdomen.

They'll see if there's any suspicious masses. So maybe we're worried about a bleeding mass. And by doing a pocus, we might actually prompt further diagnostics.

So from this, our clinicians might decide actually, we want to do a heart scan. We want to look at CT or MRI and possibly want to do any sampling if there are effusions or masses there. If a patient needs sampling, then we obviously want to check that that blood work and see that they are OK to have any needles stuck into maybe their abdomen, just so that we're not causing them any further bleeding problems.

And if they're going to require a bone marrow biopsy, again, we want to make sure that they're completely stable before they go off and have this done. So looking at platelet disorders, these will have a different sort of clinical presentation often to when they have secondary coagulation disorders. So in platelet disorders, we're often looking at patients with tiki, so that's little sort of blood marks or blood spots on mucous membranes often.

We might think about these patients showing with ecchymosis as shown here. So those are little bruises that you might see on their abdomen, maybe in their ears, so in their pinna. And if you have a light coloured patient or a patient with any shaved patches, these often become much more obvious.

Patients might actually have mucosal bleeding or oozing postoperatively, and we tend to see this in patients who maybe have been healthy and well, and maybe have gone for an elective procedure such as a dental or another procedure, a veterinary practise, and it's only when they have started to ooze postoperatively that we have had any concerns. Platelet disorders are broken up into three types. So we have thrombocytopenia, which is where we have a reduced counts of platelets, thrombocytopathyas, which is where our platelet isn't functioning properly, so an abnormal function, and thrombosis, which is where we have clotting in undesirable places.

So the platelets are working, but they are working too well, if you like. When we think about acquired platelet disorders, the most common one that we're going to see is thrombocytopenia, and in our hospitals, we're going to see primary immune mediated thrombocytopenia very commonly. We also can see this with Ryseal disease, some neoplasias such as hemangiosarcomas or lymphomas.

We might see this iatrogenically introduced, or they could have an infectious disease. Thrombocytopaths are again, these are our functional platelet disorders. So we might see problems with adhesion or aggregation or secretion.

We can see this sometimes in patients with a renal disease or maybe a myeloma, and they can be iatrogenic. Congenital platelet disorders, such as thrombocytopeniaas, we will see a hereditary macrothrombocytopenia in 50% of King Charles Spaniels, but this is luckily harmless to them. They don't often have any problems at all.

Collis, so there's I think it's a grey collie syndrome, so cyclic hematopoiesis is where these collies will have 12 day cycles in which all their cell numbers will reduce. And so we'll often see thrombocytopenia in those dogs as well. Bassets have been shown to have a congenital thrombocytopathia, although I've not seen that myself in practise.

So with thrombocytopenia, this again can happen for three different reasons. We either have a reduced production of platelets, an increased consumption of platelets, or an increased destruction of platelets. The different causes are as below.

So if we're looking for a reduced production of platelets, we'll see this in things such as aplastic anaemia, leukaemia, lymphoma, myelodysplastic syndromes, some chemotherapy drugs that we administer, and also primary IMTP. An increased consumption of platelets can happen where we have an enlarged spleen, sometimes patients who have an infection, patients with neoplasia, DIC so that disseminated intravascular coagulopathy, and patients with thrombotic pupura. And then increased destruction, the most common one again, we're gonna see this in IMTP.

Patients who have an infectious cause, so maybe hepatitis, FIV, FELV. Patients with leukaemia, again, those that we might have given some chemotherapy drugs to, and also patients who are pregnant or have recently been pregnant. So now we're just gonna talk quickly about IMTP as this is probably the most common type of platelet disorder that we're going to see in practise.

This is where the immune system of the patient is attacking and destroying those circulating platelets. It means that we have a reduced platelet count, and so therefore, these patients have an inability to clot. We often will see these patients suffer from bleeding, normally from trauma, if they've been in the hospital or, or they've been out maybe on a walk and they've done something.

And also we'll see spontaneous bleeding with those patients with a platelet count of under 40,000. To diagnose IMTP is quite difficult. It is a diagnosis of exclusion.

And so in order to do this, we want to make sure we've taken a really thorough clinical history from these these clients. We've looked at predisposing characteristics, so we know that cocker spaniels, for example, are very heavily overrepresented when we think about IMTP and IMHA. And these patients will also have full imaging so that we can see if there's a cause of this thrombocytopenia, which would make it secondary IMTP or whether this is just a primary immune-mediated disease.

Patients will have blood work, so again we'll do a CBC and a smear. They'll often present with a regenerative anaemia if they have had a bleed. We'll look at that platelet count and their clotting times.

Common causes of IMTP if we're looking at secondary IMTP are again infection, neoplasia, recent pregnancy or pregnancy, and sometimes vaccination, although there is limited evidence for that as well. The treatment for IMTP, the main thing that we're going to want to do, that we do first, is that we try to suppress the immune system. So our clinicians will prescribe these patients steroid doses, often at quite high doses initially.

If their immune system is not reduced enough, we might introduce azathioprine or cyclosporin. Hopefully, by just suppressing that immune system, this patient might be able to rally and start producing platelets themselves. But if they don't, then we want to help them increase that platelet production.

One way that we do this in hospital is we administer a dose of vincristine. So we know Vincristine is obviously a slight, a chemotherapy drug, but it also actually inhibits vagu cytosis of platelets, which means that we're helping stop those destruction of platelets in the IMTP patient. And Christine is also known to accelerate megaarcytotic breakdown and stimulate thrombopoiesis.

So it also is helping our bone marrow pump out more platelets more quickly. These patients are going to require supportive care, which we'll talk about again later on. And they may require transfusions.

So depending on how severe their disease processes, they might have already experienced some heavy bleeding. So we could look at giving this patient pack red blood cells if we're worried about their severe anaemia. We might consider giving whole fresh, fresh whole blood, which will help them with platelet numbers initially.

And we will talk again a little bit about other therapies later. So then thinking about thrombocytopathyas, these are relatively rare compared to thrombocytopenia, and we'll see a normal platelet count with these. They can be congenital or required.

And we'll see defects in adhesion and signalling of those platelets. Sometimes platelet aggregation, so the way that they're able to bind together. We'll see prevention of agonist activation or a defect of secondary signalling, and sometimes a defect in storage pool deficiency.

Three, congenital thrombopathias that we might come across. So the first and the most common one that we'll see is von Willebrand's disease. And this is a problem that is happening on the extrinsic pathway and is, causing any problems with platelet adhesion.

Our Bernardoullier syndrome again, it happens on the extrinsic pathway and is again to do with the lesion, and this can cause quite severe bleeding in these patients. Glandsman thrombosthenia is on the intrinsic pathway and is actually to do with platelet aggregation. The problem there lies with the aggregation of those platelets.

And with these patients, we'll most often see them come with mucosal haemorrhage. We can actually see these patients having acquired thrombopathia as well. With anemias, we're often likely to see a hypercoagulability.

Eremias, again, these patients might be hypercoagulable and we'll see an increase in their BMBT times. A hepatopathy might cause this patient to have a reduced platelet aggregation. Patients with IMTP or DIC might be hypo or hypercoagulable depending on the stage of their disease.

Those with leptospirosis will be hypocoagulables. We'll see these patients having bleeds. Again, with angiostrongullus or lung worm, we'll see hypercoagulability and with hyperfibrinolysis, we're going to see a limited aggregation of platelets.

We can also cause thrombopathas by giving patients drugs. So clopidogrel is an irreversible inhibitor and it's an ADP receptor agonist. Aspirin, again, an irreversible inhibition of TXA and a thromboxane inhibitor, and some non-steroidal anti-inflammatories again, will inhibit platelet function and platelet aggregation.

Hyperfibrinolysis can be acquired or congenital. We think about greyhounds a lot when we think about this, and that's because actually up to 30% of greyhounds, are known to be affected with this. Because this is a hyper fibrinolysis, so we're thinking about breakdown of those fibrin clots, we can see a lot of delayed postoperative bleeding.

In order to combat this, we want to administer antifibrinolytics and so we'll talk about that again later. And then just a note on DIC. So we know that DIC can be set off by systemic illness.

So a lot of the triggers that we might see are severe heat stroke patients and those with sepsis or sometimes neoplasia. We'll have a systemic activation of those coagulation factors, and this puts our patient into a prothrombotic state. They'll then have lots of microthrombi form in their capillaries, and this will cause ischemic damage of any organs that happen to be affected by those capillaries.

We'll then see lots of platelets and coagulation factor consumption because they're all being used up in those microthrombie. And we'll see primary and secondary coagulopathies and sometimes an uncontrolled spontaneous bleeding. And lastly on both this, this is where we have an inappropriate clot formation.

We can think about this in 3 ways. So virtual triads. So first off, we might have an endothelial dysfunction causing this hypercoagular availability.

This can happen secondary to inflammation. It might be endothelial cell activation. We can see direct platelet adhesion.

Disturbance of those platelet inhibitors and increased secretion of large von Willebrand factor. Patients in the hospital which are at higher risk of having endothelial dysfunction, those that have indwelling catheters. Those who have had multiple venna puncture sites, patients who may have recently received a trauma with cellulitis or thrombophlebitis.

Patients who are at risk of hypercoagulable states. This is where we'll have inflammatory cytokines triggering our coagulation cascade. This will increase our thrombin production.

Again, increasing platelet activation with adhesion. And we have exaggerated aggregation in response to a normal stimulus. Our activated platelets will then provide a procoagulant membrane, and they'll release agonists to perpetuate that aggregation.

And so that sort of leads into just a cycle. Our risk factors for patients in hospital at risk of this are those that have had a recent trauma or large surgery, patients with neoplasia, sepsis, and patients with autoimmune diseases, or severe inflammation. And lastly, blood stasis.

So this is where we're gonna receive a hypoxia because the blood isn't moving around as much as it should be. We'll see an increased thrombin generation. This is increasing a platelet activation and the risk factors for this in practise are going to be mostly those patients that really are immobile.

So patients who are recumbent and maybe not turning themselves frequently enough, are at risk of this. A patient who has a venous obstruction. And a patient who may be hypertensive, so a low blood pressure or a low heart rate, bradycardia.

Our clinical findings for patients with thrombosis will really depend on where that thrombus is located. Patients with a pulmonary embolist, so in their lungs will obviously show some respiratory changes. So we often see maybe an acute tachypnea in these patients and maybe a dyspnea, or possibly a cyanosis.

These patients who have had a pulmonary embolist may not necessarily need oxygen supplementation, and so they might not improve with oxygen supplementation and we'll just see sort of this persistent tachypnea. Patients who have had a cerebrovascular accidents, or blood clots to the brain, we might see an acute onset of neurological signs. This could be seizures, in which case we're going to want to treat these, or motor deficits.

And so in order to support these patients, we might have to dark in the room and sort of make changes for those patients. We can also see this in occlusion of abdominal veins, in which case we're going to see ischemic damage to abdominal organs. These patients might have an acute abdo pain where they didn't have one before.

And we might see a specific organ dysfunction. So often looking out for an acute kidney injury, so we might see that with an increased creatinine, that we weren't expecting, or hepatopathies. So in order to check for this, we're going to want to do regular bloods in these patients who are at risk of this.

If the thrombus has occluded a peripheral or a central vein, then we're going to see ischemic damage to limbs, limb paralysis, cold extremities, or non palpable pulses, all of which we can all appreciate from seeing this in aortic thromboembolisms in our cats, and sometimes swelling of the face, if this is the central vein, as we can see here in this Rottweiler. So now thinking about coagulation disorders. So again, they are acquired or congenital.

We have our vitamin K deficiencies, possibly liver disorders, the hepatitis, neoplasias or hepatic libidosis, and again, patients with DIC. Our congenital coagulation disorders are going to be things like von Willebrand's disease and hemophillias. Our clinical signs for these patients might differ slightly to those with a primary disorder.

So we're more likely to see a delayed or reoccurring deep tissue haemorrhage in these patients. They're more likely to have hematoma formations, and they are more likely to have bleeding into their joints or body cavities. This patient here on the right hand side, this little bee on, you can appreciate that she's just got a small bruise there in her umbilicus.

And this is actually called Culen sign, and that shows us that there is some abdominal bleeding, within that patient. So it's likely that she might have a haemophilia. So now thinking a little bit about what treatments we have available to us with these patients.

So if we're thinking about our fibrin clots, some things that we might want to think about are breaking down those fibrin clots and so we will look at fibrinolysis. This is where we have degradation of that fibrin clot, and plasminogen will be converted to plasmin by an activator. The fibrin is then degraded by that plasmin and the clot is removed.

Drugs that we might use to do this might be anticoagulants. So we're gonna look at aspirin, clopidogrel, rivaroxaban and heparin. We're also then going to look at antifibrinolytics and vitamin K.

So, aspirin is an anticoagulant. It is a COX inhibitor and it's irreversibly inhibits TXA2. This is necessary for, for normal hemostasis.

A dose of 0.5 mg per cake per day has been shown to inhibit normal platelet aggregation. It has been known that some patients might show an aspirin resistance, in which case they might be either increased on the dose of their aspirin that they've started on, or they might just be moved to a different anticoagulant.

There is also use of low dosing or microdosing in some patients. This is thought to actually not alter the effects of the aspirin, and so this might be an effect that we use, especially in maybe patients who are having a prophylactic use, possibly in immune disorders. So patients who may be prone to embolisms, for example.

There's little evidence to show that aspirin is very useful in cats. The next anticoagulant that we're looking at is clopidogrel. This is an antagonist of this P2Y12 receptor, which is an ADP receptor found on the surface of the platelets.

We know that we need ADP for platelet aggregation if we think back to that initial primary hemostasis. One make per kg of clopidogrel will decrease ADP induced platelet aggregation up to 3 hours post oral administration in our dogs. And as we just mentioned, our aspirin hasn't been shown to be very useful in cats.

There was a study that they did aspirin versus clopidogrel in cats with ATEs, and they showed that survival time for aspirin was about 190 days, and it was about 400 days in the cats treated with the clopidogrel. So this is a superior drug for that. Riveroxaban again is another anticoagulant, and this actually presents us with a lower risk of spontaneous haemorrhage compared to the use of heparin.

However, due to the specificity of this Riveroxpan actually inhibiting factor XA, we can't check how it's working using our in-house testing. And it is more expensive. So whether our clinicians want to use this because of the lower risk of haemorrhage, they'll have to weigh this up between it being more expensive and not being able to actually monitor its effectiveness, via doing blood tests.

And lastly, heparin, which I think is probably the most commonly used anticoagulant that we see. This inhibits thrombinin factor XA, and it prevents fibrin formation. We have low molecular weight heparin and unfractionated heparin.

We can monitor the effectiveness of heparin by taking APTTs but that is with our unfractionated only, but also looking at our activated clotting times. We can actually use heparin as a prophylactic drug in patients that are undergoing a heart surgery, for example, and also in low doses to prevent patients having a pulmonary thromboembolism. We'll use this in treating patients with venous thromboembolisms, and again, patients with pulmonary thromboembolisms.

Here is our antifibrinolytic transgysamic acid. And transexamic acid is in synthetic analogue of amino acid lysine. This reversibly binds to receptor sites on plasminogen and has also been shown to actually reduce inflammation.

As we mentioned earlier with our patients with hyperfibrinolysis, those greyhounds, we can actually use TXA prophylactically and often will. So for patients that are going to theatre that maybe we know we're going to have a big operation, it might be at higher risk, such as greyhounds or other sighthounds, we might be giving them TXA before they go in. The thing to think about is that it can actually act as an emetic, so it can make them feel really, really poorly.

So in order to try and combat this, we want to make sure we've diluted it really well, and that we've given it over at least half an hour rather than sort of giving it as a bolus dose. And this seems to work pretty well at reducing their nausea. Vitamin K is something I thought I would just mention, because although it's not really a treatment for many of these disorders, the patients who are suffering with a vitamin K deficiency, such as those who might have ingested an anticoagulant rodenticide or those with maybe some inherited disorders, we can use this to, to enable them to kind of reverse that vitamin K deficiency.

We're going to see this with prolonged PTP and APTT times. And to administer vitamin K1, we want to do this either orally if that patient is able to have it orally or IV, so intravenously, but again, we want to dilute this and give it slowly. Other therapies that we might think about include stem cell therapy or bone marrow transplants, platelet rich plasma, which is a really good short term intervention, because the platelets here will be destroyed within sort of minutes to hours of these transfusions.

But if you have a really life threatening bleed in a patient, then actually, it might be useful to provide short term hemostasis. Patients might benefit from freshhold blood, so those with coagulation factor problems, thrombopathas, von Willebrand factors or hemophillias because they might benefit from all of those coagulation factors sort of being given back to them. And also TPE which is our total plasma exchange, which is an extra corporeal treatment, and this is basically where the patient's plasma is removed and then, sort of processed through a machine and they're just replaced with fresh plasma.

This actually in combination with immunosuppressive drugs has been shown to improve patient platelet count and also reduce haemorrhage in patients. But unfortunately, there's a lot of equipment needed for this and expertise and so often this is reserved for patients in referral hospitals. So now, lastly, we just want to look at the nursing considerations for these patients.

On admission of a patient that we might be concerned has a bleeding disorder, we obviously want to place our IV. So I would recommend that maybe somebody who is very experienced and capable of doing this really gently and carefully so that we're not having repeatedly sticks, repeatedly sticking this patient that maybe has a bleeding problem. If we're going to draw blood for all of those blood tests, then we want to think about where we're gonna take this blood from.

I would say that if you have a patient that you are concerned about, then actually it would be worth thinking of drawing a lot of your blood back from that catheter if you've just placed it, to avoid having to stick the patient unnecessarily. If you do want to take it from somewhere else, that's fine, but just making sure that we're not looking at patient jugulars until we know what their clotting is like. If a patient does have a hematoma form, then just minimising harm with that.

So placing some gentle pressure on there and making a note on that patient's kennel chart so that we know where that happened and how long ago so that we can avoid that happening again. And once the patient moves into the hospital, we want to think about all of the things that we maybe do without thinking when we have every other patient come in. So for our dogs, we want to make sure we're not putting neck leads on them because we don't want to be pulling on their jugulars and putting harnesses on them so that that we weight is evenly distributed when they're taken outside for a for a week.

Kennel signs, again, are really helpful in ensuring that everybody is on the same page with these patients and making sure that staff in the hospital are all aware of that patient's high risk. So if you're having veterinary care assistants taking patients out for you, they're making sure that they're also aware that the patient needs to be harnessed, walked, they need to be, you know, kept as quiet as possible, so not jumping around, not meeting other dogs, and things like that. We want to make sure these patients are really comfortable.

I mean, we want all of our patients to be really comfortable, but for these patients, especially, we want them to have really soft bedding. We want to think about putting them in a bottom kennel or a walking kennel to reduce any accidents. And if these patients are neurological, maybe if they've had a brain bleed, for example, maybe thinking about passing out that kennel with pillows or duvets to try and avoid them hurting themselves if they have a neurological episode.

Again with these patients, we might want to consider low noise, so keeping everything really quiet. Maybe giving them soft food, especially if they've come in after having maybe bleeds in their mouth after a dental. And for patients again who have maybe had a neurological bleed or an ocular bleed, it might be quite nice to dim the lights in the ward area so that they're as comfortable as possible.

And lastly, I just wanted to have a little thought on CPR with these patients. So for any of our critical patients, especially in sort of large hospitals, we want to be discussing CPR with our clients when the patients are admitted, so that everybody knows what to do if the worst was to happen. If we have a patient that we know has a platelet disorder or coagulopathy, then we really want to have a frank discussion with the client so that we are all on the same page as to where we go if, if the patient was to arrest.

If a patient does have a coagulopathy, doing full CPR, where we are doing chest compressions and intubating is going to be quite traumatic and will cause quite severe haemorrhage. And so we need to have this discussion so that actually the clients can understand that we tend to not do full CPR in patients who are likely to have catastrophic bleeding. If clients are really, really keen on having their patient resuscitated and regardless, we will often offer a drugs only resuscitation.

And if that patient is in the hospital for a few days and we're monitoring their coagulopathy, and they have maybe increased platelet numbers for a thrombocytopenic patient, for example, then the clinicians will often revisit that with the clients in 4 or 5 days' time and have this discussion to say, actually, they've got enough platelets. We're happy to do full CPR if that's something you still want us to do. So that was today.

So we've gone through the physiology of primary and secondary coagulation. We've looked at basic haematology and how that helps us diagnose coagulopathies in practise. And we've listed primary and secondary coagulation disorders that we might see.

We've had a quick run through of the drugs that are available to us for treatment of these and know when when we might want to use them. And we've looked at the common nursing considerations for coagulopathic patients, including whether we want to resuscitate them or not. Thank you.