[00:00:00] Introduction: wWelcome to All Cats Considered, a podcast from the Feline Veterinary Medical Association.
Here we interview professionals from across the veterinary world and take deep dives into the latest evidence-based research developments, studies and guidelines that improve feline health and wellbeing.
We are the home for veterinary professionals seeking to enhance the care of cats through high standards of practice, continuing education and evidence-based medicine. In each episode you'll hear interviews with a variety of experts in our field covering a wide range of topics and the latest developments in feline health. We'll share the key points you need to know to improve your patients care.
Let's dive in and listen to this week's experts.
[00:00:47] Dr. St. Denis: Welcome everyone. I am Dr. Kelly St. Denis, coeditor of the Journal of Feline Medicine and Surgery and JFMS open reports.
I am here today with Dr. Joseph Evans and Ronald Li from North Carolina State University and we are talking about their recent Clinical Spotlight article in JFMS Clotting and Coagulation Disorders in Cats A Clinical Review of Causes, Diagnosis and Management.
Welcome to both of you. Thank you for joining me.
[00:01:16] Dr. Li: My pleasure.
And thank you for having us.
[00:01:19] Dr. St. Denis: It's nice to have you guys here. And I before we get started, I did want to say thank you so much for writing this article for us. It is such a nice, practical article that will be really helpful for people in general practice to use, you know, just to read it in general, but also have as a reference article in their practice. So I really appreciate your hard work.
I would really like to start these interviews just by saying if you could have each of you just tell us a little bit about yourself. Maybe Dr. Lee, you want to start, you know, where you how you got into this, this sort of area of research and what your current interests are for research.
[00:01:56] Dr. Li: Yeah, absolutely. So I'm currently an Associate professor of Emergency and Critical Care at North Carolina State University and so I am the principal investigator of the Comparative Platelet and Neutrophil Physiology Laboratory.
I'm actually Canadian, so I did my veterinary school at the University of Guelph and then I completed an internship in Toronto, Canada and then I went on doing a emergency and critical care residency in the UK.
And so it is during my residency that I started a project on Platelet function in dogs with sepsis and basically the interest just snowballed from there. I realized that there is a lot of areas that we don't really, really know and understand in veterinary medicine.
[00:02:47] Dr. St. Denis: Yeah.
[00:02:47] Dr. Li: And so that led to my PhD in Platelet and Neutrophil Biology at the University of California, Davis.
And so currently my research interests, a lot of my research currently are done in feline medicine, particularly in cardiomyopathy. My interest is really looking at the crossroad between thrombosis and inflammation and looking for normal pathways that we can potentially target as a way to improve clinical outcomes, especially for cats with HCM, which is one of the most common heart disease in cats.
[00:03:30] Dr. St. Denis: Yes. And I think you've also written an article for us on that as well, if I remember correctly. So, also fellow OBC grad, so kudos there.
[00:03:39] Dr. Li: Yeah.
[00:03:40] Dr. St. Denis: Dr. Evans, what about you?
[00:03:42] Dr. Evans: Yeah, so I am currently going to be a rising third year emergency critical care resident here at North Carolina State. So I'm pretty early in my research years, but my clinical interests are coagulation, endocrinopathies and kind of since it started to become bigger and bigger. Like artificial intelligence and like its applications, more like clinically in terms of, you know, paperwork and documentation and the like, medical management of things. In veterinary medicine, I did my vet school at Mississippi State and then did a rotating internship here at North Carolina and then stayed on for critical care residency. So going to be a third year, but I've been here for three years already.
[00:04:38] Dr. St. Denis: Awesome. The long haul.
[00:04:40] Dr. Evans: Yeah.
[00:04:41] Dr. St. Denis: Lot of training. A lot of training. Well, again, thank you both for being here. We're talking about coagulation disorders, so for all of us out here who don't always think about these things as much as you guys do, I wondered if we could just go through a little refresher on the three phases of hemostasis in the traditional models. So, you know, the primary, secondary, tertiary. Maybe Dr. Evans, you want to take this one?
[00:05:05] Dr. Evans: Generally when we think about the, like the traditional model, like you said, there's. There's three phases. Your primary hemostasis, secondary hemostasis, and then the last part is tertiary hemostasis.
And it's more of a model that helps us conceptualize how hemostasis works, rather than like these different pains in the body, because they're all happening all and about the same time at different speeds.
[00:05:35] Dr. St. Denis: Yep.
[00:05:36] Dr. Evans: But for things like primary hemostasis, I think a good way to think of it is just P. Primary is like platelet plug.
So that's where we generally have our, like our platelet formations, aggregation. So that comes in three steps. So you have adhesion of platelets, activation of platelets, and then aggregation of platelets.
And we can get like pretty deep into the physiology, like biochemistry of it. But really what it is is that there's a just have some sort of insult, some sort of activation for the platelets which become activated, then begin to aggregate.
And I can go, we can go into more detail, but I think that,
[00:06:25] Dr. St. Denis: and that's, that includes the von Willebrand factor. Right. So that's the factor you're talking about that's helping to activate those platelets.
[00:06:31] Dr. Evans: Yeah, exactly.
That secondary hemostasis in the traditional sense, it's the like this cascade model. So it's all of our, our clotting factors that work together ultimately to form a fibrin clot like helping attach to those platelets that become activated and really the ultimate goal of secondary hemostasis is to form fibrin. You have the two pathways, intrinsic and extrinsic.
Both of those have like different activation. Like the extrinsic pathway is NR, factor 7 that then comes in contact with tissue factor becomes activated and starts off this whole cascade. When we think about the intrinsic pathway, so our 12, 11 factors to get down to factor 10, that is kind of the amplification pathway. So we start to see that like once the intrinsic pathway becomes activated, doesn't activate itself again. And that's really where we get this cascade that where that cascade model comes from. It's just factors begin activating factors begin activating more factors to as a, from one single stimulus, just a massive activation of clotting factors very quickly rather than just a slow process.
[00:08:00] Dr. St. Denis: Right.
[00:08:02] Dr. Evans: And then again like ultimately the, the product is fibrin. So that's fibrinogen into fibrin, which is factor 1 into 1A is down from 12 to 1.
Our last part of the traditional model is fibrinolysis or the tertiary hemostasis. So that's when we start to form clots from the platelet plug and the cascade clotting factor cascade, we then have to break it down. Otherwise the blood would just become one big clot.
So it's really involving plasmin mediated breakdown fibers. So the things like tissue plasmin is an activator. Urokinase, like different molecules in the blood are both breaking down the bonds between fibrin and helping loosen up those clots as well as independently inhibiting different clotting factors when they become activated by the activation of clotting factors.
[00:09:06] Dr. St. Denis: Okay, good. Thank you.
It's something that if anyone's wanting to review it too, I mean, thank you for spelling all that out for us because the review is really good. You guys have a really nice figure in this article for people to have a look at too, just to really keep it in mind. I know some people just remember these things easily and then the rest of the of us maybe not so much.
And I think like when we talk about coagulation disorders, a lot of us think about bleeding disorders. But of course the article also talks about hypercoagulable disorders. And Dr. Li, this might be an area that you want to talk about is, you know, wondered how common these are and you mentioned HCM in cats as one of the potentially related issues. Do you want to just talk a little bit about hypercoagul disorders in cats than what we're looking at there?
[00:09:55] Dr. Li: This is my area of interest and you know, I'll try to be brief. Cats are really unique compared to other species.
The reason why I love studying platelets in cats is because I think if you think about them being carnivores and subject to injuries, it's an evolutionary advantage for them to have their activated platelet.
And so in that sense studying the platelets is really fun because they evolved have these hyper reactive platelets. Unfortunately, that also translates to thrombotic disorders.
And how common is it? Well, if we think about HCM, right. We think about one in seven cats, right. The number is much higher in older cats. And, and out of those HCM cats, we think about about 11% of them having complications manifested as thromboembolism or clot formation. The most common word is what saddle thrombus we call it. Right.
But we now also recognize that thrombosis can also manifest as a stroke-like event. Based on our recent studies that we found that a lot of cats, acute neurologic signs, deterioration, sudden death, we don't always think that they have arrhythmias, but it could be acute CNS thrombosis, like stroke-like symptoms.
[00:11:21] Dr. St. Denis: right.
[00:11:23] Dr. Li: Apart from HCM, I think another disease that we commonly see that manifests as thrombosis in cats is neoplasia, particularly pulmonary carcinoma, second most common arterial thrombus in cats and then heartworm disease and other types of neoplasia.
So arterial thrombosis I would say by far is the most common in cats. And mainly because of the activated platelets, compared to humans and dogs, they probably less likely to have venous thrombus, something like pulmonary thromboembolism is less likely, less common, I would say in cats.
[00:12:02] Dr. St. Denis: Okay, thank you. And I know with HCM, and I'm sure you can talk about this a little bit, is, you know, we're, we're looking at that two pronged medical approach to treating those hypercoagulable disorders. So platelet inhibition, drugs and clotting factor inhibition.
[00:12:19] Dr. St. Denis: you want to touch on that a little bit? Even as it relates in general, but also to
[00:12:23] Dr. Li: HCM. Right. And so that's a great question. You know, Dr. Evans did a great job dissecting what we learn in school. Right. Primary, secondary and tertiary. And we learn it as separate entities.
[00:12:37] Dr. St. Denis: Yes.
[00:12:39] Dr. Li: However. Right.
You know, during rounds, during CE lectures, I tell veterinarians that this doesn't exist inside an animal. Right. Everything happens at the same time.
[00:12:52] Dr. St. Denis: Right.
[00:12:53] Dr. Li: And so the idea of two prong approach really is that inhibiting primary hemostasis actually indirectly inhibits secondary hemostasis and vice versa, because the outcome of ATE or saddle thrombus is so bad. Right. The mortality rate is really high. We're still looking at 50%. Right. 50% mortality in hospital, really high recurrence rate.
Our effort really now is to look at what is the best prophylaxis or prevention at the time of diagnosis, Right. Before saddle thrombus kicks in. Right. So, so, and so the idea of a dual pathway inhibition, a two pronged approach where we're inhibiting primary stasis mainly by clopidogrel or aspirin.
[00:13:44] Dr. St. Denis: Right.
[00:13:45] Dr. Li: And secondary hemostasis using either heparin, low micro heparin, and more recently, a lot of research about direct oral and dicoagulin and limited outcome, limited evidence that we have right now seems to favor dual pathway inhibition more than pathway inhibition.
[00:14:06] Dr. St. Denis: Yeah,
[00:14:07] Dr. Li: yeah. And so in our practice, we usually will recommend dual pathway inhibition in cats that we think are at high risk of developing ate. So these are cats that have a very enlarged left atrium when we see smoke or spontaneous echo contrast and atrial fibrillation as well, although that's not very common. But when they have atrial fibrillation, very, very high risk as well as intracardiac thrombosis. So there's a clot that we can see.
[00:14:38] Dr. St. Denis: You can see it. Yeah.
[00:14:39] Dr. Li: In the, in the left atrium. Those are really high risk patients and we would start them on dual therapy.
[00:14:45] Dr. St. Denis: Okay, thank you for addressing that.
So, I mean, we're talking about platelets here to some degree. And I, I always call this elephant in the room platelet clump. And you mentioned cats have hyperchoil.
They auto aggregate quite easily.
And I know this is a problem. I see. I'm a consultant on vin, and we often have people that are, you know, writing in and saying, this cat is low platelets. Low platelets Low platelets, but it doesn't have any clinical signs.
And we always say we need to go back and actually really check to see how much aggregation you have.
So I just wondered if maybe Dr. Evans can talk to why it is that this is happening and what kind of things that we do with our blood samples and that predispose to this happening so that we could try to avoid seeing this occur so much in cats.
[00:15:33] Dr. Evans: Kind of like Dr. Li was alluding to earlier.
Because cats, they just tend to have these hyperreactive platelets. Like anything, any sort of stimulus can get them to start activating and aggregating because like they aggregate, they activate with really such little stimulus that there are a lot of things that can cause like iatrogenically low platelets. Right. Like when we take a blood sample, even if it's like run immediately.
Right. The cat is upset, it's activated, it's got high epinephrine response, it's freaked out, struggling, kind of fighting, trying.
[00:16:17] Dr. St. Denis: That never happens.
[00:16:19] Dr. Evans: The very first step of clinically normal, but low platelets on an analyzer can be that there's just lots of agglutination and the platelet clumps that form just from a hard stick or the cat being stressed out aren't caught by like an automated analyzer.
Really like I'd say far and away the most common thing that like we see, you know, here in RER here and all of our, for all of the patients that we've got here.
[00:16:48] Dr. St. Denis: Yeah.
[00:16:48] Dr. Evans: I'm gonna everywhere else to handling. Right. So if the, if the blood sits for too long, even in the case where we put it in calcium EDTA or like appropriately handle it, if the sample sits for too long, those platelets could still become activated, aggregate and then become falsely low.
[00:17:08] Dr. St. Denis: Right.
[00:17:09] Dr. Evans: Analyzer as well as the temperature. Right. Like if it's very hot or not put in a fridge or cooled down right away, then uh, all of those cells, red blood cells, platelets especially can still be metabolically active.
[00:17:25] Dr. St. Denis: Right.
[00:17:26] Dr. Evans: And still continue to be. And can still continue to aggregate and be well.
[00:17:32] Dr. St. Denis: so
[00:17:33] Dr. Evans: I'd say those are like the very big things for the clinically normal.
But you know, hey, this is a really scary low platelet count on our, on our analyzer. That doesn't make sense.
[00:17:44] Dr. Li: Yeah. One tip that I commonly would tell you practitioners is that especially when they're doing automated count in their practice is if their first count is low, place that tube of blood in the warmer, let the platelet rest a little bit for at least 30 minutes and recheck it again, most time the count will jump back up. It's I cannot stress. Right. And I know we certainly do it here in our practice that always, always verify your platelet count with a blood smear.
And so if you see clumps, then definitely your automated count is an underestimate.
[00:18:25] Dr. St. Denis: Right?
[00:18:26] Dr. Li: Yeah.
[00:18:26] Dr. St. Denis: And that's always a question. That's a question, actually I have for you guys is that when we're looking at like I know that in the article you talk about doing manual counts and there's a really nice box describing how to do that since we don't have people doing manual counts on anything anymore as much as we used to.
But if we're looking at a blood smear or blood film and we're looking in that feathered edge and if we detect any clumping of platelets, does that basically say, yep, there's that we need to do something else to get a number from this cat because even a bit of clumping is going to affect the number.
Like how do you interpret that? I've had people say, oh, I've only seen a couple of clumps, but to me, if you see any, that's a sign that probably can't rely on that number at all.
[00:19:07] Dr. Li: Again, I think it's always interpreting the numbers with the patient. Right. If the patient has no clinical signs suggestive of bleeding and would get, let's say, a moderately low number, declumps, likely, that number is a very underestimate. Right. It's an underestimate of true normal count. And so I would say if you see clumps and your count is moderately low, anywhere from 75,000 to above, it's likely fine.
[00:19:37] Dr. St. Denis: I say, at least in my practice over the last 27 years, the more cat friendly I have become, the less often I see platelet clumping. So we're being very minimal restraint, feeding the cat or having the caregiver petting the cat while we're doing the blood draw, things go a lot more smoothly and I'm seeing it a lot less. So I know that's helpful.
[00:20:00] Dr. Li: That's a good trick because we do a lot of feline studies and so we commonly recommend pretreating gabapentin prior to coming to see us and having a really good atraumatic. So obviously having someone in, in their practice who could hold the cat,
[00:20:19] Dr. St. Denis: it's usually me. The technicians are better at blood draws.
[00:20:22] Dr. Li: Yeah, yeah, yeah. And you know it's always the holder, right?
[00:20:25] Dr. St. Denis: Yeah.
[00:20:25] Dr. Li: And. But you know, having very atraumatic puncture is really, really important.
[00:20:31] Dr. St. Denis: Yeah, good, good. So that aside, and I'm looking at platelet counts, but now I just. Maybe we'll take a jump over looking at testing PT, APTT and ACT
Just wondering, there are some point of care tests available now in hospital.
What are the considerations that people are using point of care tests in terms of interpreting results versus sending it out to an external lab?
[00:20:57] Dr. Li: Joe, do you want to take this one?
[00:20:59] Dr. Evans: Yeah, yeah. And I think that the PTT, APTT, like, ACT, all of those are going to be testing for secondary hemostasis. So they're more focused on like clotting factors rather than platelets.
All of them have different stimuli, different times that depending on you know, PT versus PT and T versus like a, like an activated PT or an APTT, all of those have different ranges, different values, and kind of different stimuli that they use to start the reaction.
So like the point of care versus the like sent out tests. I think that for the most part the point of care tests can be like, they're cheap, they're very quick and they can give you an answer right away.
[00:21:50] Dr. St. Denis: Right.
[00:21:50] Dr. Evans: But in terms of like interpreting them, taking that sometimes with a grain of salt, like they can be very finicky. They can give us some very weird results. So
[00:22:00] Dr. St. Denis: yeah,
[00:22:00] Dr. Evans: similar to what we were talking about with the platelets, where if you have a thrombocytopenia that doesn't make sense, then maybe rechecking it or warming up the sample.
[00:22:11] Dr. St. Denis: Yeah.
[00:22:12] Dr. Evans: But for, I'd say the same thing goes for these point of care tests where like, if you get an abnormal result like the PT or PTT is, you know, markedly out of range or it's unreadable high, then kind of the first thing, if it doesn't make sense clinically. Right. The cat's got no bruising, the cat's got no like clinical signs of bleeding, then rerunning the point of care. So you know, I've found like anecdotally and then also there are some studies that show that the very first sample that's run can have a like a, like it can be falsely elevated and just rechecking it, sometimes like 30, 50% of the like of those abnormal values will resolve and be within the normal range.
[00:22:59] Dr. St. Denis: Wow.
[00:23:00] Dr. Evans: Just doing the test again.
[00:23:02] Dr. St. Denis: Right. Good to know.
[00:23:05] Dr. Li: And one thing to add also is there seems to be poor agreement between some of these point of care tests and our reference laboratory. Again, like veterinarians get these spurious results. My personally, I think PT point of care is more accurate than apt. APT tends to Be a little bit more variable, especially in hospital cases where they've received some intravenous fluids and it's inflammatory. Then I do take those APTT results with a grain of salt. And again, what Dr. Evans is saying is that, is that if it's out of range, right. And you repeat it, it's still the same. We would probably send the samples out to a reference laboratory.
Remember that the reference ranges are very different when you send those out to a reference lab versus some of these point of care cloning times, it tends to be very different. So we need to pay attention to that.
[00:24:04] Dr. St. Denis: I guess one of the last things I don't mind if you don't mind covering whoever wants to take this one. Just in regards to preparing samples to send them out for those tests in the external lab. I know there's some caveats to how, again, just like with platelets, how we deal with the sample. Do you want to just kind of talk about what we need to be careful with when we're doing?
[00:24:24] Dr. Li: No matter what, even if it's point of care versus sending it out, always, always make sure that the blood is filled to the mark that is indicated on the tube. Because of the 10%. Right? It's the 10% citrate. Any alterations in the ratio of blood to citrate will affect your test because how we test these is basically recalcifying our samples. And so if there's too little or too much citrate, it will affect our results.
[00:24:56] Dr. St. Denis: Okay.
[00:24:56] Dr. Li: And so really pay attention to those tubes. They come in different. Even they could be in the same size. But sometimes there's like 3 mils versus 1.8 versus 1.4.
So really pay attention.
A lot of reference laboratories also are very, very militant about how these are built. Right. Let's say you can't send the samples right away. What we recommend also is spending the this plasma down and immediately freezing it.
That would help to preserve a lot of the clotting factors for reference laboratory testing.
[00:25:35] Dr. St. Denis: Dr. Evans, do you have anything to add to that?
[00:25:38] Dr. Evans: I don't think I have much to add.
[00:25:40] Dr. St. Denis: Okay, cool.
Well, I just. I want to take a minute just to say thank you again to both of you for this article and I hope everyone checks this out. This, like I said, it's such a good reference article to have as I love having these types of articles in my practice. So if I can't remember something or I need a quick information when things are happening, these are really good. You guys have some amazing tables in here talking about the different hemostatic disorders. So, yeah, if you have anything to add before we close up.
[00:26:10] Dr. Evans: And I guess I think that it. It just all comes down to, like, it is very complex. There's a lot of things going on with coagulation, but I think it can be like, very easily broken down into just platelets, clotting factors, clot breakdown, and like all of those tests. I know we didn't get too much into the breakdown part of it, but really, I mean, there's lots of point of care tests. There's lots of very easily, like, cheap things that can be done in a rural practice. Like you said, you work at.
[00:26:44] Dr. St. Denis: Yeah,
[00:26:45] Dr. Evans: the MPT point of care PTT. You can get a lot of really good information just from like your history or physical exam and like a couple of tests that, that are just a few dollars to run.
[00:26:59] Dr. St. Denis: So relatively simple things and still lots of info,
[00:27:02] Dr. Li: I guess for me is, I guess, bleeding disorders, whether it's congenital or acquired in cats, pretty hard to diagnose. And I think time and time again we always teach students that primary hemostasis have mucocutaneous bleeding, minor bleeding, whereas secondary hemostasis is cavitary big bleeds.
[00:27:26] Dr. St. Denis: Right.
[00:27:26] Dr. Li: From my personal experience, cats don't follow those rules.
And so they can have primary hemostatic disorder and still bleeds like a hemophiliac cat or vitamin K, you know, so that really muddles the clinical picture a lot. I think just because a cat is having minor bleeding doesn't mean that it does not have hemophilia. So I think it does make the diagnosis of bleeding disorder quite challenging in cats because we don't currently have any good platelet of function testing that are available for practitioners. So it's pretty much a process of elimination. Right.
[00:28:07] Dr. St. Denis: Okay. Yeah. Good. And this article really helps with that, so I appreciate it. I appreciate you both. Thank you again for your time. I hope you have a good rest of your day.
[00:28:18] Conclusion: Thank you for listening to this episode of All Cats Considered. We hope you enjoyed this interview. For more information on the topics discussed in this episode, please head over to catvets.com/podcasts and explore the links in the show notes. Don't forget to subscribe to this podcast on your platform of choice so you won't miss any episodes as we release them. Have thoughts or ideas about the interview you heard today. Share them with us by leaving a comment on our Facebook page or shoot us an email
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