Has ITP Gone to the Dogs? The Parallels Between Canine and Human ITP

TRANSCRIPT

 

Dr. Dana LeVine

Canine ITP is very similar to ITP in people, specifically adult chronic ITP. Our patients seem to get ITP for the long haul and need chronic therapy.

 

Narrator

Welcome to the PDSA podcast, Bruised but Not Broken: Living with ITP. The diagnosis of a bleeding disorder like immune thrombocytopenia may leave you wondering, how can I really live my life with ITP? PDSA's podcast, Bruised but Not Broken: Living with ITP, brings empowering stories, the latest research and treatment updates, lifestyle tips, and answers to the real life questions the ITP community is asking. Here’s your host for this episode, Barbara Pruitt.

 

Barbara Pruitt

Hello and welcome to Bruised but Not Broken. I'm Barbara Pruitt, your host, and today we have a very special guest that I would like to introduce to you. Her name is Dana LeVine, and she is a professor of small animal internal medicine at Auburn University. She's a 2004 graduate of Cornell University's College of Veterinary Medicine. Dr. LeVine completed a rotating small animal internship at the University of Georgia and the Clinical Investigator program at North Carolina State University with a PhD focusing on the pathogenesis of immune thrombocytopenia. Dr. LeVine's clinical and research interests include immune-mediated blood disorders, neutrophil extracellular traps, hemostasis, and thrombosis. She recently authored, co-authored, a consensus statement for the diagnosis and treatment of immune thrombocytopenia in dogs and cats for the American College of Veterinary Internal Medicine. Dr. LeVine serves as president of the Association of Veterinary Hematology and Transfusion medicine, and she is the secretary of the Veterinary and Comparative Clinical Immunology Society. She also directs the Auburn Small Animal Blood Bank. Well, welcome, Dr. LeVine. I don't know how you have time to spend with us, but we are very honored and thank you so much for being here today.

 

Dr. LeVine

I'm very grateful for the invitation.

 

Barbara

Well, let's start off by talking a little bit about you. You seem like a, like I said, a very busy person. How did you decide to go into veterinary medicine? And more specifically, how did your interest grow in ITP of dogs and cats?

 

Dr. LeVine

So veterinary medicine, I was always a lover of animals. I grew up with pets and I horseback rode since I was six years old. So, I loved working with animals, but I also really liked science and spent a lot of time in labs as I was growing up. My mom was a researcher, and I would hang out in her lab when I was a kid. And then I started to do some summer projects in high school. And then all just naturally came together that I liked animals and science, and veterinary medicine was ah going to be a good fit for me.

 

Barbara

Sounds like you had some good role models, too, with your mom being in research. That's terrific. With you choosing to go into research, why specifically did you go into ITP research?

 

Dr. LeVine

My initial love of platelets came during vet school. It was just a summer job I took in the laboratory of Dr. Marjory Brooks, who's at Cornell. She runs the Comparative Coagulation Laboratory, and she knows more about coagulation and platelets in dogs and cats than anyone else in the world. And I just had a really great summer working in her lab, and she opened my eyes to platelets and that was, my decision was made. That was what I was going to work on for the rest of my life. And then during my residency, I saw a lot of immune mediated diseases, both destruction of red cells and destruction of platelets. And that really piqued my interest, and I wanted to understand ITP further and learn as much as I could about it in dogs. So, it's a combination of my vet school experience and my residency experience.

 

Barbara

That's wonderful. An inquisitive mind, you're looking for answers. And that's what we need. We need researchers that are looking for answers and things. So, thank you for following that path. I understand that canine ITP, which surprises people, is very similar to ITP in humans, is that right?

 

Dr. LeVine

Yes, canine ITP is very similar to ITP in people, specifically adult chronic ITP. Our patients seem to get ITP for the long haul and need chronic therapy as opposed to pediatric ITP.

 

Barbara

Are their symptoms similar?

 

Dr. LeVine

Their symptoms are very similar. They can have a range of bleeding signs just like people where their platelet count doesn't predict whether they are going to bleed or not. So, some of them are incidentally picked up just at healthy pet visits where they go in for a dental and they do a complete blood count and find out they don't have any platelets. And then others come in with severe bleeding. They can have just some petechia on their gums, some ecchymoses bruising on their belly, but they can also have nosebleeds and bleeding into their GI tract and vomiting blood, defecating blood, blood in their urine. So really a variety of signs depending.

 

Barbara

Wow. Does it happen in other animals other than dogs and cats? I mean, is it, are there other animals that are also known to have ITP?

 

Dr. LeVine

It is reported in horses, but in horses, it's more often secondary to an infectious disease. Cats, it's also very, very rare. It's much more common in dogs than cats.

 

Barbara

Oh, wow. I remember years ago taking my dog in, you know, to the vet and talking to him about my ITP, and he told me that, yeah, he sees dogs with ITP. I was was really surprised about that.

 

Dr. LeVine

It's more common in dogs than people. It's a more common disease in dogs.

 

Barbara

Really?

 

Dr. LeVine

We don't have the same epidemiologic numbers that you have, so it's hard to directly compare, but when it's not considered as rare disease in dogs.

 

Barbara

Okay, whereas with humans, ITP is considered a rare disease, because so few people have it. I know that recently, you co-authored the treatment guidelines for dogs that have ITP you, you must have seen a need for that in your community.

 

Dr. LeVine

Yeah, they're really both for diagnosis and treatment of ITP. There were no established guidelines. So just like in people, ITP is a diagnosis of exclusion, but there really wasn't a systematic approach that veterinarians were using to decide if a dog or a cat had ITP. And similarly, there were just no treatment guidelines that we would all use immunosuppression as the mainstay of therapy, but which medications to use beyond that and when to reach for other medications didn't have any clear guidelines for clinicians to follow.

 

Barbara

Wow. Well, I know that that's something that's so important. The American Society of Hematology has clinical guidelines for the treatment of ITP. And I was on that committee as a patient representative several years ago. And, you know, when a doctor diagnoses or suspects the patient has ITP, they can go to the ASH, American Society of Hematology, website and see those guidelines. Is there a place where veterinarians go to find those guidelines, or how, how is it spread out in your community?

 

Dr. LeVine

I will say that the ASH guidelines definitely were an inspiration for us, and we use them a little bit as a guide and wherever, we didn't have any evidence in veterinary medicine, we would somewhat default to the the human guidelines from ASH if they made sense for us. But in terms of access, it is very accessible. So, all of the American College of Veterinary Internal Medicine guidelines are open access. So, you can just go to their website and all of the consensus statements are available there. You don't need to be a member to access them. And the hope is that those will be used by general practitioners across the globe to at least give them a starting point and give some uniformity to how patients are diagnosed and treated.

 

Barbara

Yeah, no, that sounds terrific that there is a place that they can go because I think about the human body and all the different diseases and disorders that we can suffer from. But then when you're talking about veterinary medicine, you don't just have one type of an animal. You've got multiple types of animals. And how do the guidelines relate to other animals? Like you said, maybe horses have ITP, or with cats. Do they still follow the same guidelines or tailor them?

 

Dr. LeVine

For cats, we did, some of our recommendations were slightly different for cats, but we based all of our recommendations on evidence from the literature and in cats are really only a few case series of cats with ITP. So, a lot of it was, you know, with dogs, we had more evidence, and we said that the recommendations were stronger than in cats because the evidence just isn't out there. We did not approach horses because all of us were a small animal focused. So, we did not consider horses in our guidelines.

 

Barbara

Right. So, what's nice to know that your, your guidelines are evidence based though, you know, from reports and papers and stuff, because that, you know, from my experience that holds more weight, you know, otherwise it's just anecdotal evidence, you know, like, oh, this worked for my patient, but I don't know if it will for yours, but that's great. And the fact that you took that on, was it just you and another person that put the guidelines together?

 

Dr. LeVine

No, there, I had seven panelists. So, there were three co-chairs on our panel of seven that were internists, clinical pathologists, criticalists. So, we were the ones who led it. And then under us, we had over 40 volunteers from our profession, because we really wanted to systematically review all of the literature that was out there. So, we developed what we call PICO questions, which means that in a population, does a given intervention, compared to not using that intervention or treatment, improve outcomes? And we set up a list of questions that we then use the literature to address. And that really took a village to be able to do properly. And this was, it just, it's all just been published, but we started in 2021. It was basically a full-time job on top of my full-time job.

 

Barbara

I know it's an awful lot of work. It took us four years to get them published in 2019. And in 2019 a lot of the information was old, and there were new treatments already available that we could not include because we didn't have enough time to do all of that. The landscape is always changing, you know, with treatments and such. So, I was thinking about it also, have you in your research, have you had any recent breakthroughs or developments as far as ITP and canines?

 

Dr. LeVine

Yeah. So, we recently had a big development. It's under review. It hasn't been published yet, but we really haven't known a lot about thrombopoietin in dogs. So, as you know, on people with ITP, it can often be unexpectedly normal. And that's how come all the TPO analogs are used, TPO receptor analogs are used for treatment of ITP. We haven't had any evidence whether that should or shouldn't be pursued in dogs. And nobody had measured TPO in dogs with ITP. And the reason was we didn't have an assay. And so, I worked with collaborators at Cornell to develop an assay to measure TPO. And that took, hmm, since I think 2017. It was a lot harder to do than we'd expected. But we finally have a working assay and we're able to run a set of dogs with ITP and find out that yes, their TPO is low compared to healthy dogs. And so that sets the stage for potentially the utility of TPO receptor agonists in dogs.

 

Barbara

Right. Wow. That's great to know. Yeah. With the medications that are used for ITP patients, I know as a patient, we suffer from the cost of a lot of them. And how does that work for your canine patients? I mean, is the cost a big stumbling block? I mean, it's not as if they have insurance, you know,

 

Dr. LeVine

Yeah, some of our patients do have insurance, but the majority do not. And it is, it's a huge issue for us. So, the mainstay of our therapy is steroids. And a lot of times they're on long-term steroids. So, we don't do the the short course of higher dose dexamethasone. It's the longer course of prednisone. And then usually in plus or minus a secondary immunosuppressive drug like mycophenolate, cyclosporine, or azathioprine. If we want to do something like romiplostim, that can be cost prohibitive. In bad cases, we will use sometimes IVIG like you do, but we are limited to human IVIG. We don't have a canine one and we don't have insurance and that can be over $1,000 for a small dog and several thousand dollars for a large dog. So, a lot of clients cannot afford that.

 

Barbara

Right. And the human IVIG is, I mean, that's okay to use it in an animal?

 

Dr. LeVine

We do use it, but we are hesitant to use it repeatedly. So, we could use it in it over a short period of time, several doses, but then we wouldn't want to come back a year later because they could react to it.

 

Barbara

Okay. Yeah. And I'm sure that canine IVIG would be practically impossible to gather. I know just for human IVIG, it takes a lot of donations in order to get just one treatment.

 

Dr. LeVine

Yeah.

 

Barbara

So gosh, well, you've got, you've got obstacles there!

 

Dr. LeVine

That would be my dream. If I could find a company who is interested in developing canine IVIG, I think it would have a lot of utility in different immune diseases and dogs.

 

Barbara

Yeah. Well, I can't help but think that any type of research into our immune system has got to open doors to not just treatment of canines, but, you know, humans and any other type of animal out there when it comes to autoimmune diseases. How would you go about with your research that you do on ITP? And I know there's ongoing research all the time with humans with ITP. Is there a way to collaborate information if you were to find out something that was outstanding? I don't know. Do you all talk to each other? Is it something that that occurs?

 

Dr. LeVine

Yeah, so I have been very fortunate to have been sort of indoctrinated into the the small group of human ITP researchers during my PhD, my PhD mentor was a human hematologist, Nigel Key at University of Chapel Hill, North Carolina. And he introduced me to Jim Bussel, because I had found something in a dog model I developed of ITP, but we wanted to see if it was represented in people as well, if it was analogous in people. So, he introduced me to Jim so I could get some human samples. And we found that that it was the case in people as well. So, Jim really understands the the utility of learning from each other. And we learn a ton from human ITP, but I think there are places that the dog can maybe help people as well.

 

Barbara

Well, what was it that you actually found? Is it something that you could explain in simple terms?

 

Dr. LeVine

Sure. It was just that one of the inflammatory mediators called interleukin-8 was very low in all the dogs that had thrombocytopenia and that was, with the, so we got some human ITP samples, and it was also true that IL-8 was low in patients with ITP, and it went down with their platelet count. So it is basically this inflammatory mediator, platelets are a source of it that wasn't really recognized before.

 

Barbara

Wow. Well, that's great. I'm glad to see that there's communication and that you're, you know some of these people that are in research, like well, Jim Bussel is our you know one of our Medical Advisors, and he's been fabulous in that regard.

 

Dr. LeVine

Yeah, in fact, we just had a translational meeting, a translational summit at UNC, where we talked about different blood diseases and had veterinary and human hematology pairs. So, I spoke about canine ITP and Jim spoke about human ITP at the meeting.

 

Barbara

Wow.

 

Dr. LeVine

And I try and attend virtually the ITP breakfast every year.

 

Barbara

Oh, great. Yeah, I've been to that several times and it is very enlightening, you know, and, knowing that it can relate to your canine veterinary, you know, practices. I think that's terrific. Do you ever give blood transfusions to dogs, to ITP patients?

 

Dr. LeVine

Yes, we give transfusions pretty frequently, especially when they become anemic. Giving platelets is more challenging in veterinary medicine than it is in human medicine. I used to ask, you know, Jim and some other MD colleagues, well what's your what's your platelet product of choice? And they would just laugh at me and say, platelets, because they can go to the blood bank and get a bag of platelets. Well, I can't do that because you have to keep platelets at room temperature for five days and then and then dispose of them. And that's just not available. Yeah, it's not available in veterinary medicine. So, we often will use fresh whole blood donations because they contain viable platelets. There's also a cryopreserved, a frozen platelet concentrate that is made by a company that is stabilized with DMSO so that it can be stored in the freezer for six months. It does not work as well as fresh platelets, but it's something that at least a clinic could stock and have in their freezer if they needed something emergently and couldn't get in a fresh whole blood donor. So, we do keep that, and we have used that on occasion. Smells terrible. The whole clinic smells of DMSO.

 

Barbara

I wonder if that's ever been used in humans. I don't know. I've never heard of that.

 

Dr. LeVine

I think it may have been at one time, a long time ago, before you had better options.

 

Barbara

Because there is an issue with rural areas treating patients with ITP. If they need platelets right away, they're not normally readily available.

 

Dr. LeVine

We obviously run into that a lot. And the lyophilized platelets, the freeze-dried platelets that I know they're making for people now, we had the opportunity to use them for a few years. And then unfortunately, Cellfire, the company that makes them, decided we weren't, we weren't a profitable market, so that they're pursuing just the human side. But we all love that, because you could keep it on your shelf for three plus years, add water, and give.

 

Barbara

Wow. And I've never even heard of that. That sounds terrific. Yeah, but like you said, profit spoke louder than yeah practicality. What is your current focus of research? Is it anything in particular or is it just carrying on what you've been doing?

 

Dr. LeVine

One of the current projects that I'm working on, again in conjunction with colleagues at Cornell and also UC Davis, is looking at whether platelets lose their sugar residues or desalinated, which has been found in people where they kind of become like their old platelets early on and are cleared prematurely in people with ITP. We're looking at whether that's also true in dogs because in people that's led the way for some patients benefiting from Tamiflu and that's something we can access for our patients and is inexpensive. So, we're looking at that. We've developed a flow cytometry assay to look at that in dogs and we're starting to look at that in canine ITP patients.

 

Barbara

Yeah. Well, Tamiflu would be a lot cheaper than a lot of the other treatments for sure. So, and I know that they are, there is research, and drug development right now concerning the, what is it? Desalinization of platelets, right? So, a lot of this technical stuff goes over my head, but I feel like, you know, hey, there's hope out there, because there continues to be research and development and you know, hopefully the right treatments will come along, you know, for the treatment of ITP. How do you, how do you approach your, the owners of your canine patients? I mean, if they're like me, I love my dog, you know, and I'd do anything for him if he was sick. What are your conversations, kind of contain when you tell them they've got ITP and they have no clue what it is?

 

Dr. LeVine

We just explain, and we have to start from the basics, explain what platelets are, that it's an immune mediated disease. Usually, we have to rule out some known triggers. So just like in people, there are triggers that have been established for us. It's a lot of the tick-borne diseases, especially in the south. So, we have to do testing for that, and then look at, for evidence of any cancer with ultrasound to make sure there's not something that's triggering the ITP. Otherwise, the conversation will vary depending on disease severity, but they have to adjust to the idea that this is probably going to be a chronic disease with long-term therapy needed. If we can get them through, if they are a severe bleeder, if we can get them through that initial hospitalization, it is usually a disease with good prognosis. Depending on which paper you look at, I'd say at about a 10% mortality rate. And usually those are the ones that are having really bad GI bleeding or bleeding into their lungs or their central nervous system.

 

Barbara

Yeah, which is similar with human patients. Is there anything else that you'd like to share with us, that, regarding, you know, the research or the work that you do in any one of your areas? Because you certainly are a busy person.

 

Dr. LeVine

I think just understanding that dogs and people can learn from each other. I think one of the big advantages that we have in veterinary medicine and something that we're working on as well is genetic structure and sort of breed structure and the fact that some of our breeds are predisposed to get ITP. So, because it's a more common disease in dogs, because certain breeds are predisposed, I think trying to understand really what the underlying cause of ITP is may come from dogs. It's harder to do those studies in people because it's more rare, more sporadic in people, so I think the genetic structure of dogs, the fact that they develop ITP spontaneously, that they live with us, that they're exposed to the same sort of environmental triggers, if there's something in the environment we're overlooking, we can use dogs to help people just like we've been able to learn exciting new treatments from human medicine.

 

Barbara

Well, that sounds really fascinating because with people, we never know who's going to get it. And when you're saying that some breeds are predisposed to it, you can't help but think that there's some kind of answer there. And like you said, genetics might be the way to find some of this information out, and sharing it across species sounds like a fabulous idea. That's really great. Well, to conclude, this has been fabulous talking to you, but is there any dream or a goal that you have when it comes to what you're working on?

 

Dr. LeVine

Well, I think one thing that really started in my PhD and has continued on, I really want to understand both in people and dogs why certain people and dogs bleed and others don't, or why some are severe bleeders and others aren't. Because I think the ideal goal is to be able to really individualize therapy, to know who needs real aggressive immunosuppression, who doesn't and be able to predict how a patient will do. So that's really one of my career goals. I think the answer is somewhere in how inflamed a patient is, but initial markers that I've tried to pursue haven't panned out. So that is, that's something that I am determined to figure out.

 

Barbara

Well, I think inflammation is something that's very valuable in thinking about ITP and humans. You know, if the inflammation is higher, you could have a worse case. So, well, this has been very enlightening. I know I've learned a lot and I can't help but thank you so much for being with us today. It's people like you doing the research that are making such a big difference in the lives of, not only people, but animals too, which is a double blessing. We hope your continued research finds out even more ideas and answers to ITP. And we certainly, certainly are thrilled that you joined us today and hope that, wish you the best in the future.

 

Dr. LeVine

Thank you. Thank you for having me. I think your organization is phenomenal. And I think that all the answers lie in one health. So, the more we can work together and be a larger community, the the better.

 

Barbara

I agree completely. Thank you again. Thanks so much.

 

Narrator

How do you live your life with a bleeding disorder like ITP? From working in the kitchen with knives, to navigating sharp corners in your house, going out to eat in a restaurant, traveling on a plane, attending a sporting event, even dancing at a wedding. ITP patient, Barbara Pruitt, shares her tips and tricks for moving through life with ITP for more than 60 years. Here's her lifestyle lesson for the day.

 

Barbara

You've just smacked your leg on something, and you know you're gonna get a bruise on there, and you know it's gonna be a big one. What should you do? Well, first thing you do is you want to elevate that part of your body above your heart. So best to lie down and put your leg up, whether it's on a pillow or put your foot on the wall and keep your leg up. And then you want to put ice on that area. This will do several things. The ice will vasoconstrict the blood in that area from leaking out. Hopefully there will be less of a bruise, less of a hematoma. And elevating that part of your body above your heart means that it's going to be more difficult for the blood flow to get to that area to leak out. So, when you hurt yourself, and you know you're gonna get a bruise. Remember those two things. Elevate it above your heart, if possible, and put ice on it to help vasoconstrict that area. That's my lifestyle lesson for the day.

 

Narrator

Thanks for listening to the PDSA podcast, Bruised but Not Broken, Living with ITP. Made possible by our presenting sponsor, Amgen. Special thanks to Gus Mayorga for composing our theme music. To see what's coming up, visit our website at pdsa.org and subscribe wherever you get your podcasts. Please share this podcast through social media with anyone who you think might benefit from the information and stories we share with the ITP and other platelet disorders community. As always, please speak with a health care professional before making any treatment decisions. But know that pdsa.org is a wealth of information and resources to help you navigate life with ITP and other platelet disorders. Remember, you are not alone.