Hello, everyone. So today we're going to talk about a bit, of collaboration. The coagulation.
I will briefly talk about the different classification. Just a little bit of part of physiology. But we're going to put emphasis on practical usage and also what kind of test we could do to test our different, types of coagulation.
And at the end, we're going to discuss the therapy. As for the classification, as we all know, we have primary, secondary and tertiary hemostasis and primary involves platelets and vessels. Secondary will involve the coagulation factor.
And the tertiary is actually the fibrin fibrogen clo that's formed How it goes. How it actually will, be fibrotic. So if there's any disturbances in these homeostasis, we can have a hypocoagulability status or a hypercoagulability or even a combination of two the two situations at the same time.
As for a very brief overview, pathophysiology wise, for the, for the coagulation. So we know that the primary hemostasis it's when you have a damage on a vessel or anything, then the platelet, together with the vron factor, and also the collagen of ender cells will form a clot. And once this clot is formed, it will.
It will activate the secondary Homosassa Cascade, where all your calculation factors will group together to form a more strengthened clot. And because we don't want the process to get out of control, we actually have an inhibitory process there, the fibrosis. So it keeps the clot at an optimal size and also that it does not stay too long when the healing process has actually improved.
We're going to start with hypocoagulability, as a disturbing factor of the coagulation. So if we go back to primary hemostasis, we know that disturbances in the vessel, the platelet or the Flo fractures will cause hypo coil, in patients and for for death and the primary disorder of the he say we will have trom trom paty and Osho vasculopathy. As for thy copia, we have different kind of causes.
I'm not going to go through all of them. You can have a look on the presentation, but the main four main things is increased consumption. Increased destruction.
Immune mediated is a very important part of that decreased production because of the bone marrow and sequestration on a little side note, there are, breeds, just like the cavalier king. She that could have a non pathological beta 12 billion mutation. It causes micro thrombocytes so those will have those patients will have thrombocytopenia without being clinically inclined to have increased risk of bleeding.
As for the primary hemostasis, problem would cause, trom paty The most important one for us to know is the von Veran disease. I have a list of all the other inheritor bill diseases that can also cause, trom atopy. But I will not go further in detail into them because they are quite rare.
As for the van V libra disease, we have three types. Inheritable. Type one is when they have all their multi metres, of the fibrin factor there, but just in a reduced amount.
Type two is that you don't have the high molecular multis, which will cause increased risk of bleeding and type three. You don't have the multi there at all. I will go into detail in this disease a bit further on, but just know that there's three types in the inheritable vula disease, and then you have also the acquired V vib disease.
So other diseases can actually cause a VLA brain disease. Which is described, for example, in micro diseases in strong infection or in high E bolus of starch? Supplementation another one for the thrombocytopathy.
Except for the inheritable group like Formula One disease would be acquired because of drugs and the most important drugs that we know. And we actually also use that drug to cause trom to reduce, hyper coil would be NSAIDs, just as acetic acid. Other diseases.
It's not an excluded list. So, for example, AIA hepatopathy, anaemia, D IC they can also all cause thrombocytopathy then the third group of problems that we could have causing hypo ability would would be vasculopathy vasculopathy can also be acquired or inherited. Inherited is also a very rare disease that most of us will probably never encounter for that, the one that I see most often that could really cause a coagulopathy is vasculitis, so vasculitis can cause really big hematoma like lesions.
That is because of the, the vessels being inflamed. Other causes such as atherosclerosis or hyper coric, they can cause vascular fatigue, but usually they don't lead to hypocoagulability. As for tests to test our primary heos would be tested for the platelet count.
Beca because of bleeding time, platelet function, testing and testing for the Villa Bron factor itself, I have listed here the test that you will most likely encounter in private practise or maybe a bit in a somewhat bigger clinic. There are other tests that are available in more in research, environment that I don't think is relevant for the practitioner. So as for platelet count, we know that normal platelet amount would be between 100 and 50 to 450,000 platelets per microliter.
It is very important if your machine says that there's trom set of especially, for example, a machine that you will have, in house. Always check in a blood Mear. If that is really the case.
Because very often, as you can see here, they would hide in the periphery as a clump of thrombocytes. So always look at the periphery. Whether you see thrombocytes yes or no.
And as the breed, for example, as a Catholic kings also look out for microthrombus as well, if you have seen them. As for the proposal muco bleeding time, it is an in vivo test. So we are testing this in a patient.
So it's a invivo testing how the calculation is really running. So the the mucosal bleeding time is actually the start time where you cut the mucosa till it stops bleeding. We say that if the BNB he is, increased over four minutes, that is actually prolonged.
And it is an indication for platelet aggregation defect or villa brain disease. But the BM BT is not super, exclusive. It's not specific, so it can be influenced by anaemia thrombocytopenia as well.
Hyperemia, it is very inter operative variable as well. Depending on where you make the cut, how close you you hold the clots against the lesion and so on. And also some animals needs to be sedated to do this because they are not always willingly to let you make a cut in the mucosa.
So narcotics can also have an influence on the BM BT. As for the practical guide for doing this test is you need a timer to just time. How long the bleeding will last?
A philtre paper or a gauze response? The bleeding time template, device, as you can see here. So most people use a S cut, and for anaesthetic.
So if you sedate the patient, it depends from patient to patient. You will probably, assess. You can assess it very well in the clinic.
Whether you think this patient would need a little bit of sedation to, perform this test, if you use, sedation, do not use certain, drugs. for example, agents like ella propofol. Barbi and inhalation gas anaesthesia is all, acceptable.
But narcotic drugs you should better avoid because that can influence your, BM BT. So what happens is that you use this S cut, machine, and you can make a cut in a meco on the upper part of, the lip. And then you hold the filtration paper just underneath the cut so that it can soak up the blood that's dropping down and you count the time till it stops bleeding.
That's very simple test to do. And it's something that we do tend to do if we think there's a primary hemostasis Stasis problem, Another alternative that we will sometimes find more in the clinic settings, is a platelet function testing. So for that, you need citrated whole blood.
And you would put it in the machine. And what the machine does is it aspirate through a very small thin capillary, and the capillary wall is coated with collagen. So this collagen will actually activate the trucy going in there, and it will make a clump.
So what it measured is the closure time. So how much time this cost for the clump to completely clot the capillary? So there's no blood flow detectable anymore.
As for cartridges, because of this machine comes from the human medicine. There are three possible additives that they put on there. One is a P.
The second is AD P. And the third one is PP two Y. So as for our canine patients, it is best to use the collagen AD P cartridges because they are most reliable.
This is a screening test and not a differentiation test. So again, it gives you an indication that there's something wrong with the primary homeostasis, but it is also influenced by other factors. So it will give you an indication whether you have have enough platelets, whether there is toop paty, and whether you have vron disease, but it is also influenced by how you sample.
So did you have a clean sample? Was there already a bit clotting going on when you have been sampling? Have you waited too long after sampling before measuring?
How is the hematocrit? Has the patient have any anticoagulant medication, for example? So those are all factors that can influence the test?
As for other tests that I mentioned, that, has been used mostly in research settings, would be like transmission Amery loom agro grame whole blood a Agogo, Mery and flowy Mery. I will not go into details in these tests because, in the practise, you will probably not, come into contact with this kind of test. As for the formula brand assay, this is definitely something that you can send away.
And as a blood sample. Always check with your lab beforehand what kind of samples that they want. When they test for the formula brand.
Make sure that they always test two things. One is the quantitative formula brand factor assay. And one is the functional quality formula.
Bond factor acid so quantitative they are measuring the amount of factor protein. So how many fact proteins that you have, whether they are low, molecular or high molecular and then the functional essay, it will test the ability of your formula factor to actually interact with platelets, collagen and other, factors. It actually gives you an indication what type of a formula brand you're dealing with.
So if you have, when they are measuring the co collagen binding activity in the functional assay, they will give you an idea if you are dealing with a sample with a lot of high molecular weights of enveloper factor, because those are the ones that causes clinically, coagulation. So, for example, if you have a lot of vli factors in your quantitative essay, and you put that, compared to the collagen binding activity. So how functional your villa factor is, it will give you an indication if you are dealing with a type one V, disease patient or a type two.
So if the ratio is about one, so that's the amount of Van Brandt factor is actually causing a good amount of clotting. Then you have type one because that means that this patient actually has all the memes of the vula brant factor. If the ratio is two, which means that you have more formula gramme factors, but less function.
That means you're most likely have a type two because you have smaller M this patient most likely, causing a less functional clotting. Then the third one is also the structure formula essay. So they will tell you exactly what kind of multi mere structures you are dealing with and that you can see here on the picture.
So with those three tests, you can actually classify your patient. And the classification is most important just to have give you an idea what the bleeding risks are. So, as I said before, type one is an autosomal recessive disease.
It has full array of the multimer, high molecular low molecular has a good binding activity, collagen binding activity. So that means it has a It has a capacity to coagulate, so it has a mild risk. Of breeding.
I have a list here also, with all the different dog breeds and also cats. That you can, look through, afterwards, the type two would be no high molecular, so the binding coagulation activity is reduced. And those patients have a moderate to high risk of bleeding.
The third type is an autosomal recessive, no plasma formula bond factor. And so when you have none, you also don't have really the coagulation capability. And those, we have very high risk of bleeding.
And then we come to the secondary hemostasis. So secondary hemostasis causes, is is managed by coagulation factors. So we want to test for those coagulation factors whether they are there or not.
And if you look at the light of hyper co, we usually use PT, as everybody knows already to proto bin time and activated partial tropin time. So a P TT, and then some clinic also has AC T activated clotting time and measuring of coagulation. Factors on itself can always be sent to a commercial lab.
As you can see, here we have a very simplified model of the secondary home status where you have the eccentric pathway and the intrinsic pathway and the common pathway that we see in the middle. The PT actually measures the eccentric pathway together with the common pathway and the A P TT and AC T measures the intrinsic pathway together with the common pathway. As for the PT, So it measures the factor from starting from factor 7 to 10, 10, 5 together with, Proton bin to trom bin.
And then you have the common pathway. So when PT is prolonged and when it's mildly prolonged, you always have to see whether you have a clinical picture that shows you that the patient is actually bleeding because the specificity for bleeding is not super high when they are mildly prolonged. So if they are moderate to mark prolonged, they are quite reliable in the sense of you do have an increased risk of bleeding or your patient is already, bleeding at this time point.
So what PT discovers or tell you more information about which P TT will not do is your factor. Seven. So that's an important factor, to remember so that you know what the difference is with a P TT factor seven has a short half life.
So in early stages of vitamin K deficiencies, which we have with, rodenticide cerina and so on, you will see actually factor seven disappear first. And that means that in those cases, usually you see that the PT will prolong first as well. What is special about PT machines is that usually if you are treating the patient with heparin, the cassette actually has an antagonist in the reagent, so it will not prolong the PT.
As for the other test would be a P TT. This goes to the intrinsic pathway with the factors 11. Sorry, 1211, 9 together with eight and then you have to go to the common pathway.
So we call the 12 and 11 the contact pathway because they make contact with the plugs, the initial plugs that is made by the tropy factor and the collagen. The intrinsic pathway is where they start the cascade, and then we have the common pathway. Also here if a P TT is mildly prolonged, always ask yourself, Is this clinic clinically relevant?
Yes or no? If they are moderately or mark marked prolonged then, this is most likely clinically irrelevant here when you have prolonged a P TT but normal PT you always have to think about if those patients, for example, have haemophilia eight, which is a factor. Eight Deficiency.
Haemophilia B, which is a factor nine and then in animals, is less well described. Hemo. Haemophilia C Where you have a factor, 11 or 12 deficiency.
It is very important to note that in some cats, could be domestic short hair. They can have a factor. 12 Deficiency, which is not clinically relevant and can give you a mark to moderate to marked prolonged a P TT.
So that is just something very important to remember. If you would have a case that does not have clinical bleeding, the A P TT is really prolonged. Think about Factor 12 in a cut and think about measuring it because it could be that is an inherited deficiency that has no clinical relevance.
Other things that could prolong a P TT that cannot prolong PT would be heparin therapy, as we discussed before, with the PT and then conjunction prolonging PT and P TT together would be vitamin K deficiency, liver disease. D IC, for example, or hypofibrinogenemia. As for vitamin K?
Antagonist intoxication. Just a very brief summary about what kind of factors we are actually missing because we do not have the vitamin K, causing the reduction and oxidation process, of the coagulation factor. So for vitamins, Ok, antagonist, you have you will cause a deficiency in factor 279 and 10.
As you see here and again, Factor seven has the shortest half time life. That means your PT will probably prolong first if you're early enough at the detection phase and another test that some clinics would have is the AC T, which is very similar to the A P TT. It's also, assess the contact intrinsic and common pathway.
But it does not evaluate factor seven and factor 13. It needs whole blood. Which is not always the case, for the, PT and PT a P TT, depending on what kind of cassettes that you use.
The difference with a P TT is it can be prolonged with severe thrombocytopenia because this cassette uses the platelet in the blood sample to provide the lipid surface for the activator. So if you have a patient with severe thomen prefer to use a P TT compared to the AC T other tests to consider, doing in patient where you suspect the secondary, coagulation hemostasis deficiency would be testing for specific coagulation factors. So they have to be sent to specialised lab and depending on lab, the amount of blood and also the type of blood that they need for the test will vary, So always check beforehand before you take the samples.
This can be used actually to confirm, haemophilia a B and C all those factor 12 deficiencies as we discussed before. In cuts where you have a prolonged a P TT and a normal PT and then the third, the hemostasis would be fibrinolysis. So once you have already built the clot, we want to see, like, how is the clot actually being deteriorated?
So here you have plasma activation and also fibrin dissolution to test this, fibrotic pathway. There is also about five tests that is most often used. Which would be measuring the fibrogen itself.
Testing for the trom in time. The fibrogen degradation process testing for that and the D dimers and also the antithrombin acid. As for the fibro lytic pathway, we have the fibrinogen.
This is mostly measured by the clause method, and what it can do is it can give you a a qualitative, answer whether you have this fibrinogen or a quantitative, whether you have hypo or a a fibrinogen, it can be acquired a deficiency or congenital. So acquired would be consumption hepatic dysfunction, a congenital, it could be inhibitory antibodies and so on. Other influencing factors that can actually reduce the fibrinogen would be anticoagulants, or hyperemia or specific factor deficiencies.
As for the trombone time, what happens there is you take citrated plasma, you will add trom bins. So here and then you see the time to the first strand of fibrin formation. So you measure how long it takes for the first fibrin strand to form.
It is an indicator of fibrogen activity and concentration. So if you have a normal, fibrinogen concentration or you have a normal function of the fibrinogen, you will have a normal, trin time. If you have a reduced concentration or reduced activity, your time will prolong.
It is also influenced by other factors such as anticoagulants. Increased fibrogen degradation product can also disturb the chin time. Also other things such as hyperemia and so on.
So then we can go into the range where there's test that can reflect as well. Hypo and hypercoagulability. So when we look at the fibrotic pathway, we have also two products that we can measure.
One would be the fibrogen degradation, product. So once a fibroid clot is formed, it will also be degraded because, we cannot wait till the clot becomes bigger and bigger or stays too long, causing thrombotic problems. So what happens is that we will have plasmin.
So in the the fibrin Sorry, a fibri clot. There will be cross linked fibrin mesh and normal mesh or even fibrinogen. So it's going to be a mix of the three.
And then we have plasmin that can actually degrade the whole complex. And it lies fibrogen, for example, fibrin mesh with mono meres or insoluble fibrin and also cross linked fibrin as you can see here, it can be increased. The fibrogen product that is formed after Replacement cleaves those complexes, as you see here, it can be increased due to D IC and thrombosis.
So if you have a hypercoagulability status, it can be increased, in, for example, rodenticide intoxication. Because you are using up all your coagulation factors. There's a lot of clotting and that you have to degrade.
So that will also increase the, FDPS, and inflammatory diseases or immune mediated diseases such as I MH a You have a higher usage at the beginning that can actually cause an increase of FDP as well. And neoplasia and many other diseases that can cause actually a hyper coagulase situation or, an increased consume, of your coagulation. The second one is D dimers.
Demers is a little bit more, specific compared to fibrogen degradation product. Because D dimers is the rest product of a cross linked, fibrin mesh. That is, degraded.
So it will not degrade fibrogen the mono. It's just degrade. It just comes from degraded cross link.
fibre mesh. It has a short half life, So five hours. And that means that if your D dimers are up, you know that they were actually reduced in a very short time before.
So it's an active process going on at the moment and also here, it can be increased due to coagulation consumption and also situations that cause hypercoagulability where you have a lot of clots that also has to be built off. Then the third one would be the antithrombin acid. So to keep our body in check and that we don't cause too many clots, we actually have negative feedback mechanisms, and one of them is anti Trine.
So anti Trine will build bin bind on the trom mine and inhibit its activity. And it will also inhibits the, factor 10 activity as well. So it will inhibit trombone and, factor 10 and then some, cases also factor two.
So which is the thromb so deficiency of, anti TRM will actually causes a risk of thrombosis because this is keeping the thrombosis in check. So if you have a deficiency of this, you will build thrombus. So disease is typically that, can cause a reduction of ant.
Ant Trine would be decreased production because of the liver. There's a huge liver failure. Renal and enteric loss is a very big, cause for reduction of antine.
And also consumption associated with coagulation activation. So, for example, D IC or huge consumption of coagulation, for example, traumatic bleeding and so on. So that could cause the consumption of antithrombin.
OK, so a test that I personally, really like to use is a test that shows you or try to emulate the general hemostasis. That, those are FAS hemostatic acids. What they try to do is actually stimulate, the in vivo blood coagulation in the in vitro situation setting.
What it happens is that they will measure the viscosity and the elasticity of the sample, and two types of machine are available on the market. One would be trombo, Lato, grammes, and, the other would be rotational thrombo astory. So, rom and tech here is an example of a tech.
So what happens is that you collect whole blood, and you put the whole blood in the cup at a certain angle and the machine will put a pin inside the cup, with the blood and the pin will have an electrical current, actually causing coagulation to start to form a small clot. And this clot will cause impotence and resistance, which is translated to a graph that you can actually see here. And this graph will emulate how the coagulation happens in vivo inside a body.
If you look at the graph. So there are a few parameters that, you need to understand how to interpret the graph first is the R value. So the R value is the time that you need to form the first small plot.
And then you have the K value. The K value is a set, time that you need to reach a certain amount of strength of clot. So this is just a set string 20 millimetres.
And then you have the alpha angle. The alpha angle is actually the speed with which your clots increase in strength. And the MA is the total strength, of your clot.
So the higher the MA is, the stronger your clot is, and the bigger your clots, will be. And then we have two very interesting parameters that other tests, till now does not have is actually how they evaluate the fibrinolysis. So it will show you how the clot is actually reducing after 30 minutes, of clot formation and 60 minutes after the clot formation.
So we do expect to have a little bit of an decrease of clot strength and formation after a while, but not too much, because if there's too much, then you would have a high fibro aly situation. So here I have put a summary of all the different parameters, to check in the tech on this graph, you can actually see the different kind of coagulation stages that you have an overview of. So this is the normal one, as we discussed before.
So here, if you would have a patient with hypercoagulability, that means your clot will first form quicker. That means shorter R your clot will quicker reach the set strength. So that means a shorter K shorter time.
Your clot will quickly increase in strength. So that means your alpha angle will be higher and then it will have a bigger size and a stronger, clot. So That also means that your MA, will be elevated.
The opposite is true for hypo status, so your R will be prolonged. Your K will also be prolonged. The angle will be smaller and the complete or total strength will also be reduced.
And then the added advantage of this test compared to the other test will be the fibro analytic activity. So here you would see normal cases and here you would actually see hyperfibrinolysis. It is also not without its downsize this test.
For example, we know that the hematocrit, the lower the hematocrit is the steeper your, alpha angle and your MA will be. So that means that even if your patient is not, hypercoagulable, it will look like an a somewhat hypercoagulable graph. So here, for example, we will see it will be higher and this one will be steeper.
Another thing is that if you have a severe thrombocytopenia, you can also have a hypocoagulable state. Although in vivo it might not be the case. For example, if your platelet will be go below 50 to 75 usually we will have a hypo.
Take the thing is the question at that time point will be Does the patient have an increased risk of bleeding? Yes. But will it bleed for sure that is not the case.
Not always. For example, Typical example I always give is that, take of a patient with immunity tropia, which is often can go to zero. The tech will be completely hyper because of the thrombocytopenia.
But your animal will still be pretty lively hitting the boxes that you have put him in without bleeding risk. I'm not saying that he doesn't have an increased bleeding risk, but they don't bleed out right in front of you. So it's always very important to check the tests and test it with the clinical situation.
Another thing that can also cause, lower MA would be the level of fibrogen, which is, yeah, self explanatory, a disease that I find very interesting and has been debated a lot. Because it causes a hypocoagulable and hypo status at the same time. What can cause both at the same time will be the intravascular coagulation.
So the this, what you have here is a systemic activation of coagulation so that cause this hypercoagulable state very often it is caused by sepsis or severe inflammation. So then we have two groups. We have a non overt D IC, which has no clinical symptoms or the overt D IC, which you do have clinical symptoms that hint you or, send you in direction, that this patient might have organ dysfunction or effective clinical bleeding.
Diagnosis of D IC is somewhat complex. And but there is in human medicine, consensus that, it's best to use several different parameters and make a score out of that to see whether this patient is in D IC or not. Most use, parameters would be the thrombocytes count the PTP TT, the DN and the froo degradation product.
If you have three or more of those anomalies you most likely are in AD IC, situation and another thing to, be sure of AD IC is also to find an underlying disease that, you know, that could cause the IC two. So that will strengthen your diagnosis. Of D IC.
If the D IC evolves into a hyper probability state because they have actually used up all your coagulatory factors. Your, a lot of thrombocyte fibr factor and so on. You have a patient that actually have a bleeding risk, and it is a negative prognostic factor.
If they are there, then since we have talked about the classification and pathophysiology with the different kind of tests, let's have a look at what we can do to treat the patients with, coop parties. So we're here again. We're gonna first talk about the treatment of Hypo coil.
The major major treatment that we can do in acute bleeding cases would be transfusion medicine. So we can give those patients whole blood transfusion if they are actively bleeding. So that means they are losing red blood cells, platelets, formula, gramme factors and coagulation.
So when they're losing all of them, full blood transfusion would be the best choice. You can have, an amount between 10 to 20. Some authors even write 30 millilitres per kilogramme.
Just always look, be careful that you don't Volume overload. The patient the second transfusion. product that you could use is a fresh frozen plasma.
Fresh frozen plasma is plasma separated from the packed red blood cells within eight hours of collection, because if you prolong the eight hours, you lose a factor factor eight and then it's not a fresh frozen plasma anymore. Those are the kind of therapy you give patient that has coagulopathy without, active, having lost blood so that you don't have a severe anaemia. Moderate to severe.
Let's say anaemia where the patient actually is decompensating because of the anaemia. So here in first Roop plasma, you have milligramme factors, all the coagulation factors, and you can store that in the freezer for up to one year. Then let's quickly talk about, the rodenticide intoxication again, not the vitamin K Antigo intoxication.
So as we know that when you don't have the reduction and oxidation capacity of the vitamin K epoxy reductase, you lose factors 279 and 10. So that means that you could use the fresh frozen plasma in cases with rodenticide intoxication. But you could also use frozen plasma, so frozen plasma is fresh frozen plasma where you have kept it for more than a year, or you separated from the petro bus cells after eight hours, and you can store that for eight years.
But you cannot, like, thaw and freeze and thaw and freeze several time. Because then you will also lose some calculation factors. Frozen plasma is lower in V willebrand factor factor eight and factor five.
And, as we said before, that is not belonging to the group of the vitamin K antagonist intoxication. So we can give this, frozen plasma to patients that have an intoxication. Another thing that we could use frozen plasma for is Chlo plasma volume expansion in patient that do not respond to Crys.
Infusion. Another thing that could be used is platelet rich, plasma plate rich plasma. You do need a special centrifuge for that because, you need to light centrifuge, the whole blood so that actually, you do not separate the platelet, from the plasma and you have to remove the platelet pore plasma and store it under the room temperature under constant agitation.
So it has to go back and forth and you can store that. But, around to each, seven days. As for the platelet rich plasma, you can give one unit per 10 kilogrammes.
And you This is an indication in patient with bleeding due to throt, ofen and thrombocytopathy the same goals. If you would have platelet concentrate, which is a bit more complicated to get so usually in private practise, you would have maybe access to platelet rich plasma. But not always platelet concentration.
Depending on where you work, you can also buy cryoprecipitates, cryos, supernatant or leola. Platelet, actually. So cryoprecipitate is when you thaw the fresh frozen plasma between 1 to 6 degrees Centroid and then sediment the large, cold, insoluble proteins.
What you will get is VV factor factor eight fibrinogen, fibronectin and factor 13. The reason or the advantage of this cryoprecipitate is actually the small volume compared to the large amount of factors inside of it. So you have a less risk of volume overload if you have a patient that is sensitive to volume overload.
So here you can give one unit per 10 kilogrammes again. So those are really good for Van vibrant factor patients. So everything before before, where we discuss, the sorry, the fresh frozen plasma and the whole blood.
You can also give to five milligramme factor patients. You just have to pay attention to the volume that you have that you are giving. So here.
Sorry. What you also can give it is for haemophilia a patient because you have the factor. Eight here and patient with fibrinogen defect.
Then you have the cryos super. So after you remove the cryoprecipitate, you get all the coagulation factors minus the Vlo brand eight fibrogen fibronectin and 13. So that means you can treat it for patients with haemophilia, B and other deficiencies of coagulation factors minus these ones.
So the Leo, Leo, Leo, thrombocytes You can also get commercially depending on, where you work. And those are also a unit per kilogrammes that you could give after restoring, them in normal volume. Important if you give the transfusion, medicine is always recheck the coagulation.
So check beforehand what your PPTP TT is. Give the therapy and check afterwards. The afterwards checking is to see whether you have given enough or not.
So if you have not given enough when it's still prolonged or when you're still active, bleeding, consider re giving it, a same amount and then retesting it. As for medications that help with hypo coil situations. Would one would be decimal pressing for V vib patients.
So desmopressin is a synthetic analogue for the after arguin vasopressin, it induces a release of environ store, so that means you have to have the store. So that means in type one and two, you can use it in type three. Most likely, it will not be successful.
The other. The thing that desmin does is enhance platelet platelet function. As a dosage, you can give 1 to 4 mcg per kilogramme scrupulously half an hour before the procedure.
So if you have a VV brown fracture a patient, about half an hour before your procedure, dental surgery and so on And give that, and the Maximum Inc increment of immuno factor is about one hour after administration, and it lasts for about two hours. Just that, you know, considering your procedure that you have to, have to do one dose is enough. Additional dosing does not improve the clotting capability.
Another medication is pretty new, on the market, and that has been, used in veterinary medicine or approved, in the in the European market for veterinary medicine is it that the action is a multimodal, model model approach to promote platelet aggregation. So it actually stimulates and supports the primary coagulation system. It does that by reducing prosy cyclin stimulating the expression of pectin that is a receptor on the pickle that helps it to grab the vascular wall and cause cell adhesion.
And it also inhibits anticoagulant activity of heparin. It has a very low toxicity, has a very wide margin of tolerance. There has been studies where they have given, doses up to 200 without seeing, noticeable side effects.
So what you will do is you give this medication, before a procedure during the procedure is mostly not necessary. And after procedures, you can keep giving it every 6 to 8 hours till the bleeding stops. And this is something that you could give an patient with acquired or her copies.
And you can also combine this medication with the following medication, which is anti fibrotic drugs. As for anti fibro fibrinolysin, those are Lizin analogues. They inhibit, plasmin activity.
And as you know, PLASMIN is actually cutting the polymers of, fibrogen. And it causes, the delay of fibro analysis. So it means that once you have formed the clot, the body will be less able to degrade the clot.
And that's why you could combine this with the atoms because the ATOMY is going to help you form a clot. And the anti fibro drug will help you that clot. So that's why they work quite well in synergy.
The only thing is that you have to be careful using those drugs in combination in patient, where you actually also suspect the hypercoagulability. So the two drugs that is antifibrinolytic and one is amino acids, and the other one is Tex AIC acid. You can both use them in acquired and hereditary coag coag coagulopathy.
And you can use that also after procedures when you notice that there is a bleeding tendency or even during procedures where the surgeons that I have the impression that there's more bleeding going on here for to exam acid when you want to give a B. Please also give Merapi be because it's shown that tram acid can, actually cause nausea and vomiting when given it IV. So always give Merapi beforehand Another medication that has been described in literature, in many different papers, also with coagulation measurement, in cases, for example, with canine hecho sarcoma and so on is, Chinese herb mixture in bio to help you stop the bleeding.
That can also help a little bit with pain and inflammation. Depending on where you look. For example, in the fin there are, colleagues that really have good results with them.
But very often the information is a little bit, anecdotal, and the science or the studies are catching up to see whether they are really bringing some improvement or not. There is almost no adverse effect, reported after topical or oral administration. So that means that if you have it in, if you have the herb mix that is sterile, you can actually even put it, during the surgery on, yeah, on the surface, where it's actually being.
The problem with herb mix is that, they actually have to go through quality control to see whether they have pesticides and so on, and it is a bit difficult to get high quality un bol. Knowing that they are, they went through a quality control. As for the dosage, as I said before, you could, give it orally and also top, and you can give it for a very long time.
Then we have drugs that, control hypercoagulability, one would be plate platelet antagonists we discussed before NSAIDs can actually cause, thrombocytopathy. So here we are, using that in our advantage. So, acetylsalicylic acid aspirin is a cox inhibitor.
It reduces the function of the platelets and also reduces, the prostacyclin, produced by the endothelial cells. Those are those are the meat. This is a medication that we use more often in the past or when there's budget restriction, preventing us using the second medication I will talk about, it has, more a wide range of usage for patients that are having hyper coil risk, or a patient that actually already has a proven thrombus, for example.
So the other medication that is used more and more, is clopidogrel. It is an AD P antagonist, and it reduces attachment to one milligramme factor and fibrinogen and also production of serotonin. As for the dose, if you have a proven, thrombus somewhere, you can start with the loading dose in dogs.
It is not described, in cats, but And it has a rapid onset. Of action. Notice?
Yeah. Important to note is that, it can cause G. I upset so vomiting diarrhoea.
So try to combine it with food, which would actually reduce the risk of the G I upset. And you do have an increased bleeding risk using this. So clo grow has been used most often in cats.
With AC, M and smoke. In the left atrium, for example. It is very important to tell the owner, that if you plan a procedure as simple as a cyesis, for example, you do have to stop this medication for several days up to 5 to 7 days before you do that.
Because it would not be the first time that you would cause, small hemo, ado or hematoma. After sampling something while the patient is on the clopidogrel, then other medication that is affecting the secondary hemostasis would be vitamin K antagonist like warfarin, which which we use more often in the past. So now we use it less, because that is, a quite broad, anticoagulant.
Because it has effects on all the things that vitamin K has effect on. That means factor 279 and 10. That means you have an increased hemorrhagic risk.
So if you would use this medication, please remember to check the PT, which will prolong first because of the factor. Seven, at least 1 to 2 times per week in the first weeks. What we will use more often now is unfractionated heparin or even low molecular heparin, depending on what is available and what the owner can afford.
So in cases where you have tomo emboli effects, for example, on PTE, those are cases that you can consider using unstructured heparin or low molecular weight heparin. It binds anti Trine, with this specific polysac sequence, and because the infra heparin has an extra loop, it also has effects. On the factor two, as well.
And the factor 10. So it depends on the activity of the ant, Trine, because it binds and anti Trine, and it is also protein bound, so it means it binds. So in the T cells macrophages, thrombocytes, which makes the bioavailability less predictable.
As for the dosage, usually, if you have, a preventative, measurement where you think this patient has a hypocoagulability? condition. For example, you have, pancreatitis with severe Sears.
And you have the impression that the patient might have D IC. But it's not in the hypo Coagulate coagulable region. Before you can consider using, ruction heparin around the lower edge.
If you have, really a truss that is already there, you might consider going a bit higher in the dose. But just be careful if you go higher. You also have higher risk of bleeding.
So for monitoring of unfractionated heparin, usually we use a P TT and AC T. And your goal, of using it is actually to have 1 to 1.5 to 2 times the normal value, or the baseline value of the P TT or AC T before starting the fractionated heparin.
Alternatively, you can measure the anti 10, anti factor 10 level and your goal would be between 0.35 to 0.7.
So we also talked about the low molecular weight heparin. As you can see, the low B weight heparin is smaller in size, which makes its primary effect on the factor. 10.
So, it will bind mostly factor 10. That means it has less side effects on all the other on the other. anticoagulant factors that means less breeding.
Bleeding risk. The bioavailability is also more predictable than unfunctional heparin. But it does have a bit of a longer half life.
With the long weight heparin, you can just monitor the anti factor eight. When you want to measure it, it's best to measure it four to six hours after the uptake just to see at its peak activity. If you use it in a patient predisposed to thrombus formation, you would aim for the level to be between 0.1 to 0.3.
If you have a documented thrombosis, you would prefer to have it between 0.5 and one another. Medication that is relatively new on the market is a factor.
10 a inhibitor. So it directly binds the factor. 10 a.
And it is not anti trin dependent. So the HEPA is that we have talked about bolt That's the unfractionated heparin or the low molecular heparin. They both need ant Trine to bind the factors this medication does not need that it can directly inhibit the factor.
10 A. And it has a much less risk of clinical bleeding compared to the other. You can also use them for long term, for the monitoring.
Usually we just aim to give this dose, which is partly extrapolated from human medicine. Because we cannot Mostly, we cannot measure the, the rivaroxaban specific, anti 10 A activity, because that is mostly done in research settings or in, human, hospitals. So if you would have given an overdose of heparin, what you always can, do is give an antidote for the heparin overdose.
So I'm talking about in fractionated and also low molecular heparin. It is actually protamine. And protamine is, inactive is a form that binds heparin and form an inactive anticoagulant, and it is collected and processed from semen from salmon.
What you do is you give 1 mcg for every microgram of, or 100 units of heparin that you have given because heparin has, quite a short half life time. So if it has been a while, as you have given the heparin, you actually have to decrease the dose, of the protamine. So for every 30 minutes that you have elapsed in time after giving the heparin, you should reduce the dose by hypertension.
Give it very, very slowly over 10 minutes, or maybe even longer. So that you, reduce the risk of a reaction. And always always monitor the patient very closely.
When you're giving this, then we have thrombolytics. So those are medications that you usually give to dissolve a clot. There have been studies where they have done this with, cats with troms, bila and on the leg, for example, to see whether they add any benefits also to the survival of the patient, which is not always the case.
So that's why they have a consensus about about indications of when to use a thrombolytics. So if you have an infarction of organs that has causes life threatening situations, you couldn't consider using a thrombolytics if the infection is causing irreversible organ dysfunction and damage, think of thrombolytics or if the infection causes such severe, chronic consequences that the owner is designing for euthanasia. So if you if it's trying thrombolytics first ehan Asia, try it and see what happens.
It is very important to monitor clinical bleeding because thrombolytics really can cause clinical bleeding. If you use it locally, and the solve the clots always think that you could have to deal with reperfusion injuries such as metabolic acidosis or, noticeable or even severe hyperkalemia. So as for thrombolytics, you have septic canals, or urokinase.
What it does is it combines with plasminogen. And as we discussed before, what plasminogen actually do is it degrades fibrogen clots, so it causes, fibrogen degradation products and D dimers. It does cause a Cina does cause a systemic proto state, so you really have increased risk.
But it has a short half life. So about, 30 minutes Usually, if you give the bolus, and followed by AC R, I you do try to put your catheter close to the clots. That you have already diagnosed.
You know, K A is more fibrin specific, than streptokinase, kid ase But those actually are two medications that are not used that often anymore. In, medicine. More and more people are using the tissue plasma activator instead of the strep and neuros because they are again more specific than the upper two.
Because what it does is it binds plasminogen inside the clots. So this is a very big difference. And it causes the activation of plasmin inside the clots, causing the degradation of fibrin, causing the degradation, producing fibr degradation products.
The other two products do not do that inside the clot, but more systemic. So the two medications that can be used here is outer place and nectar place. So now that we have discussed different kind of medications, Or let's shortly discuss a case where we, could use medications and patient with a hypo coccal ability or hypercoagulability.
So we have a pumba here, a five month old shepherd mix that came to our clinic presented with severe dyspnea and coughing. When we did all the diagnostic tests and so on, we saw that actually, the dog has a very strong, strongly Azor infections or long worm infection, causing, most likely lung bleeding. According to the radiographs, at a certain point when he was coughing, there was a little bit blood, in there as well, because he was so dyme he actually had to be ventilated.
Due to the breathing difficulties and ventilation problems, what we did in this dark with blood, in our blood exam is that it shows, a regenerative anaemia. The hematocrit was not super low. The thrombocytes were normal.
But if we did our D IC profile, So when we did the PTP, TT, fibrogen and D dimers initially, you can see that they are prolonged. So here again, if you look at the upper reference range, the PT and P TT is prolonged, but they are what we would call mildly prolonged. The fibrinogen is significantly increased.
Which is probably the body trying to meet the demand of the coagulopathy and the D dimers is also increased, which we meet, which we know. That means that platelet the plas are actually being degraded. So for us, with the changes we do say that the lung worms are causing AD IC in our patient here.
So what we had in this patient is a debate between, the internal medicine department and our EECC department. Whether or not we should give this patient, an plasma transfusion, yes or no. Because the PTP TT are actually not super prolonged.
As we said before, if they are mild, they know they don't always have, clinical relevance. But on the other hand, we do have the suspicion, as you can see here in radiographs that there is lung bleeds. And what the heis afterwards?
Yeah, we will show that there is bleeding. What the lung was also did, as we discussed before is that it can also cause a thrombocytopathy, so it might not always have to do, with, your secondary homeostasis coagulopathy. And what it also can cause is actually hyperfibrinolysis.
So if you would, cause a clot or produce a clot, it might not last as long. And because there is clinical indication of bleeding, and the values are abnormal. We did give the patient plasma transfusion, and we also added tram acid in the hope that when it builds a clot, it can actually maintain the clot, and we can reduce the bleeding.
So the patient was then ventilated had a plasma transfusion is getting tram acid because we wanted to kill the worm slowly, to reduce the risk of an embolic thromboembolic event. We used Femina zole so that we give every day a dose. And then as soon as we think that the patient is better, we actually stopped the tram acid, so we did not continue giving it.
Because if you have AD IC you, you are actually in a situation where you have hypercoagulability so you don't always want to increase the risk of thrombus formation with treatment of the trans exam asset. And also we know that when the warms, it can also cause thromboembolic event. And so you don't want the tram acid to increase that risk.
So we gave that at the beginning to hopefully stop the lung bleed. And once we have depression proximately under control, we actually stopped giving that. The other reason is we also started prednisolone, when we started the prenazone treatment to temper the inflammation caused by the dying of the wounds inside the body.
And we know that prednisolone, causes a hypercoagulable state. So once it has a hypercoagulable state, we actually don't always want to combine it with the Texan acid. So that was the reasoning.
In this case, if the patient would not. So, for example, if the patient would have been in a in AD IC situation and you do not have clinical indication of bleeding, and it would be, for example, other cause, causing the D IC, you could actually consider in those cases to use, an anticoagulant such as, the low molecular heparin. But in this case, because there was clinical bleeding, we, of course did not use that treatment.
And luckily, pumba made it, so he slowly improved. Could have been weaned off of the inhalation therapy. And it was quite happy and be able to go home.
So I thank you for your attention, of this presentation. If there's any questions, you can, relate it to our team. And I will see if I can answer that.
Thank you.