Hello, everyone. I hope you're well. Welcome to this webinar when we're gonna be talking about the bleeding patient.

So we're gonna be going through hemostasis, talking about how we investigate a patient with a bleeding disorder. And then we're gonna look at some disorders of primary hemostasis and also secondary hemostasis. So these patients can be quite challenging.

The picture on the left is a dog that we saw that was bleeding from its mouth. From its oral mucous membranes bleeding into its gastrointestinal tract, this animal actually ended up having thrombocytopenia, so a significantly low platelet count, which was presumed secondary to, a new mediate platelet destruction. So let's just start by reviewing hemostasis.

So you can remember that if a vessel is damaged and it's platelets then that become activated, they change their shape, they stick to each other and . Platelets secrete substances from, from granules which causes platelets to stick to each other, and then ultimately that platelet plug gets formed which it temporarily fills the hole or the damaged area to a blood vessel. And of course we also need that protein which is called von Willebrand's factor.

Which is required to anchor those platelets to the, to the damaged vascular endothelium. So, this is primary hemostasis, you need platelets, you need enough of them, you need working platelets and you need this protein Bombrellarans factor. But that platelet plug doesn't last very long, it's quite unstable.

And so that's where we have secondary hemostasis coming along, and that platelet plug becomes stabilised by the deposition of fibrin. So let's just remind ourselves about secondary hemostasis, and you'll probably remember you've got those coagulation proteins or coagulation factors, which you've got Roman numerals, and there's sort of three parts of the secondary coagulation cascade. We've got the intrinsic, the extrinsic, and the common.

That's the sort of classical way of looking at it and, and for ease or stick with that, but actually it is more more complicated than that and there's a lot more crossover between those different pathways. So the intrinsic pathway is the one on the left, so if you have damage to a surface of a vessel, you have exposure of calliarin, that protein, you activate the intrinsic pathway. And then you can see at the bottom that that joins into the common pathway.

The extrinsic pathway, which is sort of simpler in its way, because that's only factor 7, is activated by release of tissue factor from cells. So, particularly in things like infectious conditions, inflammatory conditions, there may be tissue factor which is contained in a wide variety of cells might become released. And, ultimately, each successive factor activates the subsequent factor, which results in the formation of fibrin, which is then cross cross-linked in that clot.

But of course, we don't want excessive clotting happening and so we do also have that mechanism called fibrinolysis or tertiary hemostasis. So that's where that fibrin clot is broken down by the activation of plasmin, which is derived from plasminogen. And when plasmin breaks down, so a big component of that clot breaks down, you get release of fibrin and fibrin degradation products, and also something called D-dimers.

And you might remember that you can measure things like fibrin or fibrinogen degradation projects, and the diamonds as a marker of disseminated intravascular coagulation, which basically means there's lots of clots getting formed which are then getting broken down, which is one of the main things that happens in DIC. So that's just a brief overview then of hemostasis, primary, secondary, and just touching on tertiary. So what about the clinical signs?

Well, it, it's sometimes relatively straightforward to differentiate whether you think a patient's got a disorder of primary or secondary hemostasis based on clinical signs. The problem is there's quite a lot of crossover between the signs, and many of the patients that we see in practise have got disorders of both primary and secondary hemostasis. So in the primary hemostasis patic or ecchymosis are common, so I'll, I'll show you image of those in a moment.

We often see bleeding from mucous membranes, so that can be things like the nose, the oral mucous membranes, sometimes the gastrointestinal tracts as well. We sort of think of that as a Mucous membrane in the context of an animal having a primary hemostatic disorder, and often these patients bleed from, from more than one site. Whereas in patients with secondary hemostatic disorders, they rarely have TA or achymosis.

They can do occasionally. They tend to have deep or cavity bleeds, but they can also bleed from mucous membranes, hence my original statement that there is quite a lot of crossover. And more commonly there seems to be a single site of bleeding.

If you see hematomas, they're much more common in animals with disorders of secondary than primary hemostasis. But as I say, there is crossover and many patients that we see can have disorders of both primary and secondary. So yeah, these are some of the signs in animals with primary hemostatic disorders, so petia, which are those small blood spots usually less than 33 millimetres or less, and then when those coalesce into larger areas, there's ecchymoses which are, defined as being areas of 10 millimetres or more.

Between 3 and 10 millimetres, that's what we call papura, which are again sort of evidence that the patient has got most likely disorder of primary hemostasis, and it is just a close up, usually they're more apparent on the oral mucous membranes or the sclera sometimes. What about, secondary, signs of secondary hypnostasis disorders? Well, as I say, body cavity bleeding, we normally think of sort of abdomen and thorax.

But it can also be things like the mediastinum as well. We often think about central nervous system or joints as well as a body cavity. So that's where we see patients with disorders of secondary hemostasis more commonly bleed into and as I say, it may just be one site of, of bleeding.

So, if we think we've got a, a patient that's got a disorder of primary hemostasis, how do we, how do we go about sort of trying to, you know, work out what, what's going on? Well, as I said to you earlier on, if you think about the physiology of hemostasis, it's about, platelets, being enough platelets, those platelets need to function, and you also need to have vobieran's factor and so. If you've got a deficiency or an issue with one of those things, then you may have a disorder of primary hemostasis.

So, how do we, how do we test for disorders of primary hemostasis? Well, the most common disorder of primary hemostasis is to have insufficient platelets, and the most common cause of insufficient platelets or a thrombocytopenia, is to have immune mediated destruction. So, it makes sense to first assess platelet numbers.

But these are on the slide are also other tests of primary hemostasis. So focal mucosal bleeding time, vonbuebrand's factor antigen, and not commonly done, but thromboellatography or or Tg. And we'll just briefly touch on some of those things.

So a platelet counts, you know, I'm sure you know how to do a platelet count. I don't want to dwell on this, but the important things are that you try and take a, you know, a fresh blood sample as possible and a cleaner blood sample as possible, because state platelets do have a, you know, predisposition to sticking together. So you should make a smear, you should firstly check the tube and make sure there's no clumps in the tube.

Gross clumping. If there is, you need to take another blood sample. If you find the platelets are sticking together quite a lot, sometimes putting the blood into an into a citrate tube rather than an EDTA tube can help.

So you make your blood smear, you then, look for evidence of platelet clumps, and that's normally in the, Feathered edge, which is where the larger groups of cells, white cells, groups of platelets tend to accumulate. So look for platelet clumps. If you find this platelet clumps, there's no point going on and starting to count the number of platelets.

You need to make another, take another blood sample and make another blood smear. So it's not normally something you've done in the Smearing, it's normally that the platelets have been a bit sticky in the tube. So take a fresh sample.

So look for platelet clumps if there aren't any, then move further backwards to the monolayer and go on to high power mag magnification, so that's oil immersion and then count the number of platelets per high-powered field. And also know the morphology of platelets, whether there's any big platelets, macro platelets that might suggest there is platelet regeneration, a bit like a macrocytic red cell, suggests regeneration. So count numbers of platelets per high-powered field, several high-powered fields and take an average and and multiply that number by about 20.

To give you an approximate platelet value of, a number that's, times 10 to 9. So, take that value, multiply it by 20, it gives you an approximate value of platelets per 109 per litre, which is, of course, what machine, the machine count that platelets give you. So, you know, you're sort of looking to take you into the normal range, you're sort of looking for, you know, 10, 8, 10 platelets per high powered field.

So that's just to remind you about the different parts of the, of the blood smear. We're gonna start on the feathered edge, looking for those platelet clumps and then move a little bit further behind where we have platelets in the monolayer, but we want to avoid going too far backwards when the. When the red cells and other cells are superimposed on top of each other because it'll make things very difficult to count and you can clearly see in that bottom middle photograph that there's, you know, significant numbers of platelets there.

What about another test? This is one that people often ask about as a test of primary hemostasis. So remember, thrombocytopenia is the most common cause, so it makes sense to check platelet numbers first on a machine count or by making a smear or combinations of both.

And but the bumucosal bleeding time can occasionally be useful. It's, if you've ever done it, it's, it's quite challenging to do. You have to have a very compliant patient.

So it is a test of primary hemostasis, but it basically gives you sort of a global assessment of primary hemostasis. So don't, you know, do this if the platelet count is low. It doesn't give you any extra information and also, also, you know, always check the platelet count first.

Because if the patient has got a very low platelet count, a, this will be prolonged and that doesn't give you any extra information, but B, these patients can, you know, bleed excessively, from the site that you conduct the buckle mucos or bleeding time. So it will be prolonged in patients with insufficient platelets, if they've got a platelet dysfunction, if they've got Bombalaran's deficiency. So it is just a test of primary hemostasis.

I would, if I ever use it, I will use it after I have assessed platelets. So platelets are normal and I really still think this patient has got a disorder of primary hemostasis, at that point, I might do a Bcal mucosal bleeding time, because if it's prolonged, it tells me that, yes. That patient does have a disorder of primary hemostasis, so I need to go in to look for the cause, whether it's a thrombocytopathy or maybe von der Lebran's disease.

But if your bu mucosal bleeding time is relatively normal, no, that means the animal doesn't have a disorder of primary hemostasis, and so you need to maybe think, could it have a disorder of secondary hemostasis. So you need to use one of these bleeding devices, there's various ones out there, basically a little sort of spring loaded device with a couple of blades that fire out. So as you can see from this image, you lift up the, usually the, the top lip of the dog or the cat, and then you put the device against the gum, avoiding any obvious vessels, and you press the little trigger switch and.

Two, usually two little blades come out, and then you use tissue paper or philtre paper, whatever you've got to hand, and you, make sure you start a stopwatch as well when you fire the fire the switch, and you just stop that blood running into the animal's mouth, but it's critical that you're. You know, philtre paper, your paper towel, whatever it is you're using doesn't touch the incision sites because that's what we're wanting to monitor those incision sites for when you see a primary clot forming. And there's reference ranges and textbooks, but it's normally around sort of, you know, 10 minutes, give or take.

So we do know it, it changes with sedation, we do know it, it can potentially change with breathing things, so it's still relatively crude. Most animals with a significant disorder of primary hemostasis, you know, the bucklemurs or bleeding time will be significantly prolonged, you know, you'll, you won't have stopped bleeding after 20 or 30 minutes, so you don't, you know, not really worrying about whether it's the reference interval is 89, 10 minutes. Just a brief note on tag or thrombolesography.

It's generally only available in referral centres. It's definitely not something that you can post a sample to an outside laboratory because you need to analyse that sample, sooner rather than later, and it, it sort of gives you a global, assessment of coagulation, so the primary, secondary, and, and tertiary. And you see, you might have seen in, in books, you know, patterns like this, and it can tell you if there's .

Potentially a problem with You know, platelet function, whether it's a problem with fibrianalysis, whether that patient's got sort of DIC like state, etc. Etc. But for, for most people, it's gonna be out of reach and and to be honest, we've got tag, but we don't use it very often because it's it it's, it's quite variable, to be honest, in the sort of traces that we get and .

There was, you know, there's, there's data suggests that maybe it doesn't really correlate very well with sort of clinical disease and things. So I think it's a bit more questionable nowadays. So, what about disorders of secondary hemostasis?

So we talked about primary hemostasis was thrombocytopenia, thrombocytopathia, vobiebrand's disease, and we will actually just touch on some of those at the end of the presentation. What about disorders of secondary hemostasis, well, you've got the congenital ones, which is haemophilia, and acquired, which is anticoagulant rodenticide or rat bait toxicity, and then hepatic disease. But a note on patients with hepatic disease, though these animals don't spontaneously bleed with hepatic disease.

You only worry about coagulation round about the time you're sampling them, so the time you're doing a, a liver biopsy. That's why we assess coagulation around about the time of a liver biopsy and you remember that not only does the liver produce the majority of the coagulation factors, but it activates 279, and 10, which are the vitamin K dependent factors, and that, and that's normally what animals with liver disease are deficient in those vitamin K dependent factors. Hence why if we need to do something to them prior to biopsying, we give them vitamin K.

So yeah, there's a variety of inherited factor deficiencies. There's slight breed predispositions. Haemophilia A and haemophilia B are the most common ones, although they are still very uncommon in the patients, that you'll see in practise.

So haemophilia A is a factor 8 deficiency and haemophilia B is a factor 9 deficiency. So these are gonna be, generally they've got significant haemophilia gonna be patients present at a young age, maybe spontaneous bleeding, it may be excessive bleeding around the time that you're doing surgery like a neutering surgery. And then when you assess their coagulation times, you find that only one part of their secondary coagulation pathways are, are affected, and then you can send samples to external laboratories to measure individual coagulation factors, and we normally send a blood sample off to measure factor 8 and factor 9 because those are the most common hemophillias.

So yeah, what about tests of secondary hemostasis? Well, very crudely, we've got the whole blood clotting time or slight variation on that is the activated clotting time. We've got the one stage prothrombin time, and then we've got the activated partial thromboplastin time.

Sometimes those are those those terms are shortened to prothrombin time and partial thromboplastin time. And then, as I alluded to you, you can measure individual factors, not that commonly done in practise, but it's possible to measure individual ones. And it's important when you're taking blood for an assessment of coagulation, that you try and do it as cleanly as possible, because what you don't want to start doing is damaging the vessel, because if you're doing that, you're gonna get coagulation already starting.

So take from a, from a, A vessel that's been minimally traumatised, you may think you should take from, you know, a larger vessel, like a, a jugular vein, but if you do think that that patient has got a disorder of, hemostasis, take it, take blood samples from a peripheral vessel, because then at least you can put pressure over those vessels if there is excessive bleeding. Whereas a central vessel like the jugular vein, you're gonna struggle to stem bleeding if the animal bleeds excessively. So let's just run through a case.

This was Jessie, who is a 5 year old female neutered spaniel. So you might be thinking already spaniels, immune-mediated disease, could she have ITP? It's a very common disorder of, hemostasis.

She's got 2 days of lethargy, hematosis, and dark coloured faeces. She's up to date with vaccines and she receives, topical, advocate every 4 to 6 weeks. She's only access to the garden and is generally walked on the leads.

There's no history of toxin ingestion. She's not travelled outside of the UK, so we'd be less concerned about, you know, infectious conditions that might affect hemostasis, things like Elichia, for instance, Elichia canis particularly. And there's no other dogs and no other pets for that matter within the household.

So when you examine her, she was depressed, she got pale mucous membranes, a bit of a delayed CRT. Her heart rates increased and pulses are a little bit reduced in strength. She's slightly tachyne with a respiratory rate of 60, but when you listen to the chest, it's relatively unremarkable.

You palpate your abdomen, but just generally quite tense. You can't find the specific, specific focus of pain. And her faeces, yeah, were, were dark on rectal palpation, but her temperature was in normal, normal limits.

So what are her problems? Well, she's got hematemesis, dark coloured faeces, that the owners noted, and also you noted on clinical examination. She's tachycardic, she's tachyneic, and she's lethargic or depressed.

And so I'm sure you've already been taught, and we've touched on this, the problem orientated approach. So it's where you think of an animal's problems and you try and prioritise them, hence why I've called lethargy depression, which is very non-specific at the bottom of this list, whereas say hematosis or bleeding through the gastrointestinal tract are pretty significant problems, they're at the top of the list. So we try and prioritise our problems and then we think about differential diagnosis and we try and prioritise the differential diagnoses.

So you could have a think about some differential diagnosis and see what you can see what you can come up with, maybe stop the presentation at this stage. So, maybe have a think about hematosis, what differentials could you get for hematosis? So these are some that I came up with, you may have slightly different ones, you may have more, you may have not thought about some of these things.

So this list is definitely not exhaustive. So I tended to split them into sort of, you know, gastrointestinal diseases and then, you know, extra gastrointestinal diseases. So GI diseases might be inflammatory disease like gastritis, IBD maybe ulceration, of course, that's quite a common one, especially in patients that have had non-steroidals or steroids.

Might be secondary to hemorrhagic gastroenteritis, you know, that, that condition or syndrome when we see excessive bleeding from the GI tract. We often don't understand the cause. People think it might be clostridia related.

Maybe that patient's bleeding from it, . Oesophagus, of course, and, and vomiting, not that common, but occasionally we see it. Maybe that the guts are ischemic, so there's been, you know, significant blood loss or fluid loss.

You know, maybe that patient's got hypoadrenal corticism. We could see GI bleeding in patients with Addison's disease due to gut hypoxia, and neoplasia is another good cause of gastrointestinal tract bleeding, either bleeding from the tumour itself, or because tumour has, you know, eroded mucosa. And then extra GI diseases, again, Addison's is a sort of a shock-related thing.

Animals with mastocytosis, one or more mast cell tumour can, can bleed because they get excessive histamine release, and histamine, of course, secretes gastric acid. Pancreatitis again, it's probably sort of hypoxia related thing, and then uremia, we can occasionally see GI bleeding in patients with with uremia. And of course, quiteiopathies, so we need to think about whether it could be a primary or secondary.

And then also don't forget about ingestion of blood, you know, could this animal have nasal disease and it's, you know, swallowing blood? Could it have oral pharyngeal haemorrhage and again swallowing? Could it have respiratory tract disease, haemorrhage, and it's coughing up blood and then swallowing it again?

So you know, if this was for your patient, what would you do next? Do you think about doing some, you know, a blood transfusion, do you think it needs that? Probably not at the moment, but it might be worth bearing in mind that it could do.

Maybe do some imaging, think about haematology, faecal or cold blood. Well, at least the latter, I wouldn't do that because this animal's got gross, gross blood. Remember the sort of cold blood is looking for microscopic amounts of blood, so there's no point doing that.

I think at this stage a haematology would be super, super sensible, wouldn't it? And this is the haematology from this dog. And you can see that she's significantly anaemic.

Her hematocrit's down around, 0.2, so, you know, equivalent of 20%, and that's manifested by, her other sort of red blood cell parameters, the count haemoglobin being reduced. We asked the question whether it looks like there is a regenerative or a non-regenerative anaemia, looking at the smear, looking at MCB.

MCHC is important, and you can see that the cells are of a normal size and there's a normal amount of haemoglobin in them, so it doesn't look like it's regenerative when you'd expect big, bigger cells, and macrocytic cells with less haemoglobin, and that's also. The case from the, smear examination. Good thing is that platelets, at least on the machine count and then confirmed by the smear, are well above the sort of number that animals bleeding, and that number is 50 times 10 to 9 or less.

In reality, it's often much less than 30 times 109. So we've got significant anaemia, no evidence of thrombocytopenia, so that's good. What else is going on?

Your ear is high. That may be pre-renal aotemia. It could be high protein diet, or it could be lots of protein in the gastrointestinal tract, secondary to bleeding.

So look out for high ureaas and particularly if there's a suspicion of a patient that's got a bleeding disorder, or maybe that's on drugs that could cause ulceration. High ear could point you to the fact that there's lots of protein, I, you know, plasma proteins in the gastrointestinal tract that are getting broken down, to by ammonia to be excreted, as urea. And the liver enzymes are a little bit elevated, the ALT and also the ALP, but that doesn't necessarily of course mean that this, this dog's got liver disease, as we alluded to.

Previously, of course, animals have commonly got elevated liver enzymes if their liver is a bit unhappy, and this dog's liver is likely to be unhappy because it's got significant hypoxia. So yeah, what would you do next with this patient and you know, we actually did or this dog actually had a whole blood clotting time done. Word of caution, it is very crude.

So a whole blood clotting time, you take a sample of blood, usually a few millilitres, and you put it into a plain glass tube, ideally, so one without any sort of anticoagulant. And you time how long it takes for a, for a clot to form. And the reference is sort of, again, it's, it's sort of variable, but it's usually less than about 8 or 1010 minutes.

And there's a lot of variables. So, you know, you ideally need to try and keep blood at body temperature, so 37 degrees, so at least keep it sort of warm in your hand when you're doing this. But it is quite crude.

It varies depending on the temperature, size of the tube, how much blood you put in the tube and things. So, If a patient is actually bleeding in front of you, you know, there's an OK correlation between the whole blood clotting time, and the risks of that patient bleeding, but this, this is something that should never be done as, say, a, you know, a pre-liver biopsy test cause it's far too, far too crude. So we would rarely do this.

Luckily we have access to prothrombin time and partial thromboplastin time. So, APTT assesses the intrinsic and the common pathway, so those ones on the left, whereas the one stage prothrombin time or short and just a prothrombin, assess the extrinsic and the common pathways, the one on the right leading into the common pathway. And you can see that those are prolonged and for completion our sort of coagulation testing includes the dimers which I alluded to with the breakdown products of cross-link fibrin, so it might be something you check for if you think a patient's got disseminated intravascular coagulation.

This dog's got prolongation of the intrinsic extrinsic common pathways. So what sort of things cause those prolongations? Well, disseminated into vas coagulation, so I'll mention that 2 or 3 times, just to remind you that is a a condition, it's not a primary disease, it's, it's a result of usually another condition, so quite big and significant conditions like heat stroke or snake bite, or pancreatitis, as, as some examples of things that often lead to tissue damage, tissue factor release, and then you get activation of hemostasis.

But then again you get activation of tertiary hemostasis, so those start to get broken down, and then it gets to the point when you or when the patient uses up the platelets and clotting factors and uses up the anti-clotting factors, and so the final result is spontaneous bleeding. So they sort of go from a hyper to a hypocoagulable state. So as I say, usually secondary to sort a major underlying disease.

Haemophilia, could cause, prolongation. But it usually only just causes prolongation of one of those pathways. So, most of the time it's APTT because we've got haemophilia A and haemophilia B and that intrinsic pathway.

We can get anticoagulant rodenticide toxicity causing prolongation of APTT and OSPT. And we can get hepatic disease causing a prolongation of both of those, because of course the vitamin K dependent factors are present in all of those different, different pathways. So yeah, which of these do you think this dog, this dog could have?

Well, the owner actually then retrospectively reported that she may have had access to an anticoagulant rodenticide, but it's going to be the most likely cause in an animal that has a disorder of secondary hemostasis that's got prolongation of both the the intrinsic and the extrinsic pathways. Because DIC animals are normally very unwell and there's a big underlying cause like the pancreatitis, snake bite, heat stroke, big tumour burden. Haemophilia is a congenital problem, so the animal would have presented early in life with bleeding or around the time of surgery.

And as I say to you, it only affects one of the pathways. Hepatic disease doesn't lead to spontaneous bleeding like this dog appears to have spontaneous bleeding, so, you know, . By elimination, ultimately anticoagulant anticoagulant anticide is the most likely.

You can actually go and test for, the various anticoagulant rodenticides, and it's quite useful to do that if the owner doesn't have any information about what the animal could have ingested, because it dictates how much you should use vitamin K, which is the, the management, the treatment for anticoagulant rodenticide toxicity. But just a note on managing patients with either a primary or secondary coagopathy. You want to avoid subcutaneous injections because you risk big hematomas developing.

You want to be very careful with intramuscular injections because of course muscles very vascular, you could get excessive bleeding. You wanna minimise invasive procedures and you want to handle these patients quite gently. So that might mean that, you know, you keep them hospitalised so they can't get damaged in the home environment or if they are at home, the owner's very careful, doesn't take them on walks.

So, it's just some sort of general management strategies. So yeah, what about the anticoagulant rodenticide toxicity? Well, there's a number of, it's normally second generation anticoagulants which are out there, being, being used, .

The two beginning with B are probably the more, more common ones that we see. Difenaum as well is quite difficult. You aren't able to generally purchase that yourselves, but, licenced.

Licence, pet, officers will have access, access to that pet controllers will have pest, sorry, pest controllers will have access to that. And they cause depletion of the vitamin K dependent factors 279, and 10, which are in, of course, different of those pathways. You usually, but not always, develop clinical signs a few days after exposure, but it can be quite soon with a large dose of anticoagulant rodenticides.

And so what, what happens is that the rodenticides inhibit the active ingredients in the in the rodenticides inhibit a particular enzyme, this one here, vitamin K epoxide reductase, which converts vitamin K from an inactive form to an active form. So vitamin K is created by the liver in an inactive form requires this enzyme to activate it, and it's this enzyme which is inhibited by the anticoagulant rodenticides. Factors in both the intrinsic and extrinsic pathway become depleted.

So that's why you can have why you usually have prolongation, of both the prothrombin time and the partial thromboplastin time. But in fact, factor 7 has got the shortest half-life. So that's, that was in your extrinsic pathway, the one on the right, and so we often find that that pathway becomes prolonged, prolonged first, so your one stage prothrombin time becomes elevated first shortly followed by your, partial thromboplast in time.

In reality, when many of these patients actually come to us bleeding, they've got prolongation of both of the, APTT and the OSPT. So as I alluded to earlier, if you, if the owners don't have information as to the specific anticoagulant rodenticide, you can send the sample to an external laboratory and they can try and assess whether that patient has had exposure to warfarin or the the other types of anticoagulant rodenticides, because it then allows you to determine how long you should treat these patients for. And the treatment is with vitamin K.

If you happen to, or if you happen to get presented with a patient that the owner has seen that they've ingested antopcoagulant rodenticide quite recently, as in within the last, you know, 2 or 3 hours type of thing, then the standard. so the approaches to the poisoned animal work, so you induce a mess, use gastric lavage, you may use activated charcoal as well, but, you know, the vast majority of these patients present when they've got signs of bleeding, meaning they ate they anticoagulant redactantide some time ago. And several weeks of treatment can be required, and vitamin K can be quite expensive, so owners need to be, need to be aware of that.

They can have a require a prolonged course of vitamin K. And these are the different doses, and these are informries or the veterinary poisons Information Service, which if, if you, if you haven't joined, I would encourage you to do, it's got some super useful information either online or when you email them or more commonly actually speak to them on, on the phone. So, as I say, most of the, anticoagulants are the second generation ones nowadays, so you're gonna be treating for about About 3 weeks.

And what we normally do is to check the prothrombin time, and the one stage prothrombin time. Usually about 72 hours or so after the last dose of vitamin K has been given because that pathway, the extrinsic pathway, the one on the right hand side of my diagrams, is gonna become prolonged first if that animal's still got Still got anticoagulant rodenticides hanging around in their, in their system. So we yeah, we normally, normally assess that.

And if that patient has got a prolonged PT we normally then give vitamin K for about another week and then retest again. And if it's normalised, then we can stop vitamin K. In the patient, you know, that is actively bleeding, you might need to use whole blood or red cells if they're significantly anaemic, or fresh frozen plasma or again whole blood for the coagulation cascade for the coagulation factors.

So, so that was, the most common disorder of secondary hemostasis, which is, vitamin K, antagonist injection or anticoagulant rodenticide ingestion. Others we said, are the hemophilas, very uncommon, really, but young animals presenting at a young age with bleeding around the time of surgery, liver disease we also talked about, but those patients don't spontaneously bleed, we just worry about bleeding at the time of taking a biopsy. So what about back to the disorders of primary hemostasis?

Well, as I've previously alluded to, the most common cause of disorder of primary hemostasis is insufficient platelets, so thrombocytopenia, which is usually immune mediated. So, yeah, have a look at the immune-mediated diseases presentation for further details. What about other less frequently identified causes of a primary hemostatic disorder.

So again, just to remind you, primary hemostasis, you need enough platelets, you need the platelets to be functioning and you need von Beebrand's factor. So you can already guess what condition this Doberman might have. They are predisposed to developing von Willebrand's fat deficiency.

So yeah, what about thro platelet function disorders or thrombocytopathias, not that common. It can be congenital, which are very rare or acquired. Acquired ones, as we're seeing them, and second and most likely drug-related.

So if you ever have a patient presenting with bleeding, finding out about drug history is important, particularly things like non-steroidal anti-inflammatory drugs. And then, von Willebrand's factor deficiency, congenital, it's much less common than it was 1020 years ago because of widespread testing and breeding, breeding out of the condition, particularly from a breed like a Doberman. There are acquired von Millibrands factor deficiencies.

People think that some animals with angiostrous pozorum as an example, develop like an acquired von Millibrand's factor deficiency. So yeah, what about the platelet function, disorder, so thrombocytopathia? The inherited or the congenital ones are, are quite uncommon, but these are just some examples of names that are given to them, and there's certain breeds, as you can see here, so Persian cats develop, a certain type, Basset hounds another type, German shepherd dogs are a different type of thromboscytopathia.

So if you have a young animal that's bleeding, you think it's got sort of primary hemostasis, and maybe you've assessed platelet numbers, they've got enough platelets, but you've then gone on to do a buckle mucosal bleeding time, which is prolonged, you know, have a look in the textbook, have a look online and just see whether your patient, your, your breed or the breed that you're faced with has got any reported congenital or developmental thrombocytopaths. So those are just examples of them here. And as I mentioned earlier, the acquired ones, drug induced is probably the more common ones that we see, particularly secondary to non-steroidals, hence why we use aspirin as an anticoagulant historically, less commonly now.

Platelets can also stop functioning with diseases of the bone marrow. So, sort of myeloproliferative or lymphoroliferative diseases like leukemias, lymphomas, multiple myelomas, occasionally other bone marrow disorders, toxins, possibly infectious causes of bone marrow disease, but, but not very common. But luckily, animals with thrombocytopathys are not very common because they are quite, quite challenging to diagnose.

So these animals again, they're going to have a normal platelet count or near normal, definitely nowhere near the 50 times 109 that leads to spontaneous bleeding, but they're gonna have a prolonged bocal mucosal bleeding time. They will have normal levels of ombrebrand's factors, so that could be your approach. You have a patient with a disorder of primary hemostasis, platelet numbers are normal or near normal.

You then do a buck of mucosal bleeding time and it's prolonged. Next thing to consider checking is von Bilebrand's factor, and if that is within the reference interval by exclusion, it's highly likely that this patient has got a, platelet dysfunction. And if you were to want to try and go on and and test for that, one way to try and do that would be to do thrombolotography or tag, but again, that's not widely available.

What about management of a patient with a thrombocytopathia? Well, you know, there isn't specific therapy to get those platelets working. An obvious thing is to withdraw any drug, like particularly like a non, a non-steroidal.

Non-steroidals with glycosamine and glycans have, have been reported to occasion result in quite severe thrombocytopathia. So, if you ever have a patience on both of those, that's bleeding, that could definitely be a cause. Platelet transfusions are now possible.

So you may be aware that the pet blood bank can supply you with, packed platelets. So for you to give a platelet transfusion, it's sort of platelet concentrates. It doesn't have a particularly long shelf life, so you tend to not be able to keep it in stock.

It only lasts about 2 weeks, very maximum. In the fridge. But, you know, you can order it relatively quickly.

So if that patient has got a very significantly low platelet count and it's bleeding, that could be a lifesaver getting, platelet concentrate or packed platelets. But this patient, of course, that's also bleeding may need other support by way of, say, a blood, blood transfusion. OK, let's just have a think about another disorder of primary hemostasis.

So remember we said that animals need this protein, Bombriillibrand's factor, which helps anchor those activated platelets to the damaged endothelium. And So it, it plays, plays, sorry, a really important role in in platelet adhesion, and it's actually released from endothelial stores after ADH gets released. And also after, exercise and after, stress.

So it's a very glycosylated, quite large protein. And there's different types of Wambrilla brands factor. So there's type 1, there's type 2, and there's type 3, sorry, different types of von Bebrand's disease.

There's type 1, there's type 2, type 3. It is, although it's still relatively uncommon, it is the most common inherited bleeding disorder in dogs and probably cats as well, although it's particularly rare in cats. So it is more common than the Then the disorders of secondary hemostasis.

So, there's 3 different types, Type 1, type 2, Type 3. Depending which of those the animal has, it, it leads to different bleeding severities. So, type 1 are when patients have low concentrations of a structurally normal protein.

And they may have very mild signs, variable signs, may not actually have an apparent bleeding disorder or they may only bleed after, you know, surgery or significant trauma. Whereas patients with type 2 have got structurally abnormal, von Bilbrand's factor and often have very severe clinical signs that can include spontaneous bleeding. Animals with type 3, not only, do they have, they have virtually no von Berbrand's factor.

Those don't clinically present that often because they probably die in utero or they die at birth with excessive bleeding. So it's normally the ones you'll see are patients with type 1 or sometimes type 2 hombrebra's factor. And we know there's a whole range of breeds that are predisposed to developing Bombarabrand's disease, and as I say, luckily it's less common nowadays because we have tests for it, genetic tests for it, and, you know, selective breeding has reduced the incidence of the disease, at least in something like the Dominuler, which is has a very high or used to have a very high incidence of this disease.

Many breeders will test or many owners will still test for this, this disease before they breed, and it's useful for you to be aware that there's definitely a number of Doberman pinschers that do have von Bebrand's disease. So, particularly if you've got a young Doberman pin that you're doing a, a routine surgery, maybe an ovarian hysterectomy or a castration, it's prudent to assess their clotting ability. So by doing a mucosal, a sorry, a buckle mucosal bleeding time is a, is a sensible thing to do.

So yeah, do that prior to surgery in these patients. It may be that owners have already done some sort of testing beforehand, genetic testing and the others, there are some good genetic tests to identify this, this disease. So animals with umbrella band's disease typically have signs of primary hemostatic defect.

So the ones we talked about before, things like mucosal, haemorrhage, so nose, mouth, maybe gastrointestinal tracts. They may show some bruising, they may show signs of TKI or ecchymoses. They may bleed excessively from surgical sites or from traumatic wounds.

Gain, particularly those patients with type 2, type 3 disease might have quite profound bleeding from mucous membranes, from the urinary system, gastrointestinal system, at the time of the stress. Bleeding from the mouth at the time of tooth er eruption or possibly at the time of a coarse parturition. So yeah, how do we diagnose 1 millibrand's disease?

Well, these patients have, A normal or near normal platelet count. Definitely not anywhere near that 50 times 10 to 9, they would be worried about spontaneously bleeding, but they'll have a prolonged buckle mucosal bleeding time, so a few minutes is sort of normal. If they've got the sort of type 1 form, it's gonna be maybe a little bit prolonged, but again, it's quite a, it can be quite a crude, test to do.

But those patients have got type 2, type 3, you're gonna have a significantly prolonged booking mucosal bleeding time, and often you'll You know, give up on, looking for any signs of, of clotting, you know, and finish the test, and they're still not, still not clotted. So you can send a blood sample away as an alternative rather than doing a vocal mucosal bleeding time or to complement it to an external laboratory and ask them to measure the actual protein levels. Occasionally labs ask you to send a sort of control sample, but often they'll use control serum.

And they'll give you a result that's compared to the control that you've sent or they've got that tells you how much von Willebrand's fat protein that a patient of yours has has got. Although there is data suggests that it doesn't necessarily always predict the risk of haemorrhage. But if you've got a patient, you know, that is, that is bleeding or a Doberman pre-surgery that you decide to measure the amount of boviebrand's factor, you know, I would act on the result, i.e.

In the patient that you haven't yet done surgery, you know, be cautious about doing surgery unless it's essential. In the patient that's actively bleeding, you know, you may need to do something like give them blood. So say there are genetic tests out there and available in in the UK and other, other countries as well.

What about the treatments, fresh frozen plasma or cryoprecipitate, which is basically, so the plasma that's been concentrated down has got a, and has got a higher amount of umbiobrands factor in it can be, can be useful to stop bleeding. Of course, these patients may need red blood cells if they've haemorrhaged significantly and are significantly anaemic. You can also give desmopressin, which is synthetic ADH, and we said that ADH causes endothelial cells to release vombilebran's factor.

So you can, can give that if you had it in stock, people use this around the time of bleeding or as a sort of prophylactic thing around about the time a patient is having surgery if they suspect or know they've got von Blebran's disease. OK, so I hope you found that session useful, so we talked about physiology of hemostasis, we talked about primary hemostasis being platelets, sufficient platelets, functioning platelets. And volos factor.

And then we talked about secondary hemostasis being, of course, that coagulation cascade that gets activated by release of tissue factor or damage to vascular endothelium, and then activates those sequential coagulation factors, resulting in cross-linked fibrin. And then we said that tertiary hemostasis is when you get plasmin, . Release, which is breaking down, cross-linked fibrin.

And we went through disorders of primary hemostasis, so not enough platelets, most common and most common cause of that is immune mediated thrombocytopenia, may have a problem with platelet function, thrombocytopathia. So it could be drug related. It could occasionally be congenital, which you may see in certain breeds.

And then we just chatted about von Bileban's deficiency. And then for the animals with disorders of secondary hemostasis, could be the hemophilas, so A and B, most common. Generally young animals, not, not that common.

You can measure specific coagulation factors. Could be liver disease, although we said that patients with liver disease don't spontaneous bleed. We only really worry about, coagulation testing around the time we're gonna do a biopsy.

But the far most common cause of an animal with a disorder of secondary hemostasis is anticoagulant rodenticide toxicity. And we went through, through a case of that and said that these patients have usually got prolongation of their intrinsic, extrinsic and common pathways. So they've got prolonged APTT OSPT and And then we talked about managing those patients by way of trying to find out what type of anticoagulant rodenticide they've got, and then managing them by way of vitamin K and then monitoring them with your coagulation testing usually sort of 48, 72 hours after you've stopped their vitamin K and you may need to continue the vitamin K if their coagulation time or times are still prolonged.

So yeah, I hope you found that useful, and thanks for your attention.