ITP - You’ll be cruising when you see bruising!

[Music] Continuing education credits for physicians and other healthcare professionals are provided by VCU Healthcare Continuing Education. Check out cribciders.vcuhealth.org for more information. The cribciders podcast is for entertainment, education, and informational purposes only. The views and statements expressed in this podcast are solely of those of the hosts. Welcome back to the cribciders. I'm Chris the Cheomancer. And I'm joined by my co-host, Dr. Sam Mazer. Say hi, buddy. Hey, and our super producer, Jennifer Chisholm. Welcome back. Hi, very happy to be back. So tonight we have a great guest, Dr. William Bo Mitchell, here to discuss ITP. We're very excited about this episode, but first, Sam, remind us what is this show about? Chris, I would love to remind you about what the show is about. We are the Pediatric Medicine Podcast. We interview leading experts in the fields to bring clinical pearls, practice changing knowledge, answering lingering questions about core topics in pediatric medicine. We have a fantastic conversation with our guest, Dr. Mitchell. Dr. William Bo Mitchell is an associate professor of pediatric hematology oncology at Cham Children's Hospital at Monte Phil, where he is director of hemostasis and thrombosis. His primary clinical focus is pediatric hematology, with expertise in diagnosing and treating rare bleeding disorders, and with a special interest in platelet disorders. Dr. Mitchell's clinical research has focused on novel therapies for rare bleeding disorders and sickle sorenemium, and his basic science research has focused on mechanisms of action of novel ITP therapies, platelet function in sickle sorenemium, and the production of platelets from stem cells. Dr. Mitchell teaches us the fundamentals of how to recognize, diagnose, and manage ITP. Jennifer, I think people will really like this episode. Should we get into it? Well, we have a lot on our plate, so let's simplify the topic. Welcome Dr. Mitchell to the show. Thank you. Thank you. I'm very happy to be here. Because we're sort of an informal group, is it okay if we call you by your first name? Is it Bo? Yes, Bo is good. Excellent. So just a little warm up, you know, just to get to know you for our audience. Can you tell us a little bit about yourself and maybe something that's non-medical that you want us to know about? Sure, I'm a platelet biologist. My favorite cell and subject is the platelet, and most of my patients have problems with their platelets, which is why they come to me. I love classical hematology and all things hematology. I've been doing this for quite a while, and so I've seen a lot of stuff, which maybe we can talk about during this interview. And something that's not medical, I love to build things like cabinets and I used to, I was a carpenter before I was a doctor, so I used to build barns and houses now. I just built cabinets and furniture. Wow. That's a hobby. Do you use, do you like hand tools or do you use a lot of machinery? I do the hand tools, actually. I do all my cuts, and it's fun. It's a learning curve, but it's fun. Very cool. What have you made most recently? Most recently I finished a nice cabinet and my wife's study. The project before that was where I'm sitting. You can't see it, but I have a floor to ceiling, with a 15 foot ceilings cabinet with space for library books and closed cabinets and a nice walnut desk for me to sit at. That was a lot of fun to make. Very cool. Very cool. Amazing. Jennifer, you got a question? Yes. As a resident, I feel like I love hearing guests answer this question because it always makes me feel a little better. But I was wondering if you could tell us what is your favorite failure and what did you learn from it? That's a tough question because I have a tough answer to it. One of my most special patients of all time had inherited immune disorder and we couldn't figure out what it was and could not figure it out. Then finally, after about a year of being at my president institution, we figured out what it was and we found genetic cause for it and we found something that could be a targeted therapy for it. We started that and maybe they were getting a little better, maybe not, and we kept trying to do everything we could to reverse this process for this person because they were really getting more and more ill as time went on and then COVID hit and this person got COVID and it never went away and she succumbed to COVID eventually. I felt like such a failure because I felt like we had worked so hard and we were so close to having something that would help treat her. What I learned from that was the only thing that the parents and the family cared about was that they knew how much I loved their daughter and that was the most important thing to them. They didn't care less about all these genes and immunology and special medicines. They just wanted to know that I had really cared for and loved their child. That was a big fail and a big win at the same time. Lesson learned. Thank you for sharing that. I'm definitely going to remember that. Yeah, that's super special. I don't know if my next question is really, you know, has much to compare against that, but I think we've all learned from that piece and appreciate you for sharing that. I will kind of take it a little bit in the opposite direction, more from the positive standpoint if that's okay. The best advice, we are all growing, we're all trying to learn. Is there any advice that you'd recommend? Either advice you received as a learner or advice you received as a teacher that we think that a listener should know? I've had a few great pieces of advice over the years and one that really resonates with me is, and I think of it every day, is that no matter the advice is no matter what the situation, how difficult it is, if you approach it with patience and courage, you'll be able to solve it. So I always try to remember that patience and courage. Excellent. Excellent. Should we go ahead and jump into some cases? Yeah, let's talk about platelets. Does everyone want to talk about platelets? I think that's what people are here, right? I feel like that's what people are here for. Let's do it. Jennifer, go ahead, read the case. Let's be honest, keeping up with Pete's literature is hard. Over a million new articles have put up that every year in only a handful really change how we care for kids. But if you missed a few articles that matter, it means missing out on better care for your patients. That's why we're into JournalFeed. JournalFeed.org is written by practicing pediatricians who scan the literature and send you quick, high-yield summaries of the most important piece and primary care articles right to your inbox every weekday. Each summary gives you the bottom line up front, the quote, spoon feed, plus a super short, practical summary. You'll get smarter in just two to three minutes a day. It's fast, it's easy, and honestly, it's fun, and you can even earn CME credit. So, Cribsenders listeners, try JournalFeed free for seven days and get 20% off your first year with CodeCrib25 at journalfeed.org/cribsenders. That's journalfeed.org/cribsenders. CodeCrib25. So, I am a case from cash-like children's outpatient clinic. So, Violet is a three-year-old girl who presents to a PCP for an ED follow-up visit. One week ago, she was seen in an ED with URI symptoms and had a CBC check. Violet's father reports that the ED doctor told them to follow up because the CBC showed a low platelet count of 38,000 and was otherwise normal. Violet has recovered from her URI symptoms. And when you ask about bleeding symptoms, Violet's dad noticed that she, just in general, always has a lot of bruises as an active three-year-old. It hasn't noticed any changes. So, to begin with, could you begin by taking us through how you are thinking about a patient like Violet based on that information and what different rules you'd be considering? That is a great case. I have all kinds of light bulbs going off on my head. The first thing that I'm thinking about is the presentation. So, combination of a viral syndrome with low platelets makes you sort of jump on the acute or newly diagnosed ITP, Ben Wagon, but then the platelets are not that low. And they're not really not that low enough to have acute bleeding. And the timing is kind of funny because the platelets usually don't drop until after the viral syndrome. And so, it makes me wonder if this girl has ever had a normal platelet count. So, I'd really want to find out from her pediatrician issues ever had a platelet count before. So, my other light bulb is that this could just be the uncovering of a inherited platelet problem. So I would want to follow, go down both of those paths and see what Seward falls out. And before we even kind of talk about work up and stuff like that, we are going to talk about ITP. From a differential diagnosis standpoint, it sounds like malignancy or other types of things. Those are not really under differential with a case like that. Is that correct? You're really thinking of two big, big things. And I was just wondering why that's the case and kind of how your differential is just kind of two categories. That's a great question. One of the things that one of the most important things that I've learned as a clinician is to tell when a child is extremely ill or is not extremely ill. And I've seen enough kids with leukemia to tell that those kids are usually really sick and they don't look well. And I've seen enough kids with ITP to know that those kids usually look fine. And they are usually bouncing off the walls to everyone's distress. And they don't usually look seriously ill like the kids with leukemia have. So I was about to say I've been wrong once, but I wasn't wrong because I never actually diagnosed them with ITP. I made them wait and wait. And after a couple of weeks, they presented with leukemia. So it does hold true that for the most part you can tell a really sick kid from a really well kid. One quick question. So we've said the word ITP a couple times. Can you help us define exactly what ITP means and maybe some of the pathophys? Sure. The current meaning is the immune thromocytopenia. So ITP. The first iteration of that was idiopathic thromocytopenia, which idiopathic because we didn't know what caused it. And thromocytopenia, because the platelets were low and it was causing bruising or apropara or ampeticia. But that's been shortened to immune thromocytopenia because now we know that it's an immune-mediated disease. And we know that it's the thromocytopenia is the cause of the bleeding symptoms. And so it's a simpler, a simpler name. The pathophysiology of it is very complex. The general big bucket of diagnosis is the immune system, which has somehow decided that the platelets are foreign antigens and is making antibodies against them. And then those antibodies are taken up by the macrophages and the reticulate and dithelial system of the liver and the spleen as well. There are many other ways to get immune thromocytopenia. And it's probably a kind of a one bucket for many different types of immune processes that turn out to have the same phenotype. So some people with ITP are not going to respond to the usual therapies. And so they probably have ITP of another flavor. And they need a different type of therapy. And so we're finding pockets of people with ITP that don't respond to the usual therapies, but they'll respond to something else. So it's a we don't really have a really specific diagnostic terms for those patients. So they all have ITP. But they do, we are separating them out into different phenotypes. If we bring sort of the conversation back to Violet Out 3, so you'd mention that sort of one thing that you're thinking is, you know, IDP tends to present to children who is well-apuring bouncing off the walls. Can you tell me a little bit more about how you see ITP commonly present? Sure. The most common presentation is a child about Violet's aid. Typically coming to the emergency room, sent by the pediatrician, covered from head to toe with spots and bruises. They, for some reason, they all are just bouncing off the wall and really unnerving everyone. And their platelets are usually extremely low. So I can see in the single digits. That's from the hospital point of view. That's kind of the most common presentation that we see. In the clinic, we see the patients with the more and city's onset, who maybe don't have symptoms, but their platelets were found to be low on a their annual visit CBC. And those will be referred just to the clinic and we'll we can evaluate them there. And those are, they're a little different. They respond a little differently sometimes to therapy and they're kind of a different cat and they're a little older than usually the teenagers. So they're a little bit of a different category than the younger school age kids who give the full on ITP with super low platelets. So you're mentioning ages. What age group is ITP overall most common in? It's most common in adults actually, but there's a peak around school age kids. So in my experience, anywhere from like three to seven, those are the kids that we see mostly that get the very low platelets, usually a viral presentation and then they usually with or without therapy get better after a few months. The teenagers, the older kids, those kids tend to have not so low platelets and they tend to not necessarily need any therapy. And they also tend to not necessarily resolve in a few months. So a lot of those will go on to become a chronic, which is after a year of having a TPA. Yeah. And one sort of final follow-up question about this common presentation as someone who's sort of a resident and still kind of hurting my clinical feels, I do find it tricky sometimes when it comes to bruising, especially in the toddler age group and for young children. Sometimes they have so many bruises. What's kind of your role of thumb of, you know, in, for example, a toddler age group, what degree bruising would start to concern you or strike you as abnormal? So one rule is that the bruises should be flat. If they're if they're really raised and you can really feel them and they're human tomas, that's not normal. If they hit themselves that hard and got a human tommorow, they probably need to go to the emergency room. But you and then the other thing is the size. So people with platelet disorders often will get bruises the size of their palm, like they can be really big. And typically regular bruises are smaller. Even on active toddlers, the bruises are usually relatively small, like a centimeter or so less. But the bruises with ITP can be very big. And really alarming looking. That actually brings up a follow-up question at what plate in your experience, at what platelet level would you expect to have kind of bruising or end-or symptoms? What's your kind of cutoff in your head? It's actually a really tricky question in ITP because the patients with ITP sometimes don't have bruising or bleeding even down to platelet counts in the single digits. Whereas if my platelets went to 10, I would be bruising and bleeding a lot of the place. So it's a little trickier in the kids with ITP. So I don't really tell the parents, if there's no bruising or bleeding, the platelet count is fine because that may not be true. The platelet count may be 1000. So it's difficult to tell an ITP to be honest with you. But generally, around 10,000 or so, you start to see more bruising and particular. And then the mouth lesions and all of that. So if I'm at 30 to 50,000 or something like that, I might not have any symptoms regardless of what my disease process is. And then you were kind of mentioning also that platelets, we gave the patient the initial platelet count is 38,000. Is there a level with which you'd say this could be ITP or not ITP? Do you have a cutoff, for example, on your platelet number? Well, the definition is under 100. So anything under that, really. I think the highest platelets that I've seen in ITP is, I think it has the highest platelets in ITP. I have had a patient in the 90s, in the 90,000s. So it does get up that high and it can be a little variable. So my next question is, say I'm the pediatrician seeing this child. And based on physical exam, I have ITP higher, my differential. I'd only just done like a quick CBC just because I was worried. And now I think it is, what type of workup should I be doing in the office setting? Or is it something that I need to send directly to the hospital? Or what would I be doing? What would I be testing? My advice for what workup to do after you get that platelet count is send them to some place where they'll be seen by a hematologist. So send them to the emergency room. If they don't have a lot of symptoms, send them to our clinic. We, and most other hematologists, will see a patient with low platelets the same day. So that's, it's an urgent matter that should be looked at pretty quickly. I'll follow that up with. Yeah. We love to try to figure out, and this show, what is happening at that first office when we see that sub-specialist. So say we refer over there. What test are you ordering then? And what are you looking at so we can kind of do that next step if we want to? - So I am doing my assessment from the door. Is this a very sick child or is this a well-child? I'm doing my exam of them. What are their bleeding symptoms looking like? Are they someone who's covered with bruises in particular or are they somebody who doesn't have any bleeding symptoms? And those are two different buckets of patients. If they are a school-age child and they're covered with bruises in particular and they're having some bleeding in the mouth, then I need to go down the path of figuring out, do I want to treat them? And what lab tests have to happen before we can do that? If they're a teenager and they're play-as-they're not that low, I'll probably want to do just a basic immune type workup and we can talk about that a little bit too, but then go down the path with them. So a little bit different depending on how they look. If they look ill, then they're going right to the emergency room from clinic. - I see. So if you are sort of thinking about doing a bit more workup in clinic because they're not sick looking, what sort of that initial workup, so you mentioned sort of immune workup, would that be an A and A immunoglobulins anything else? - Usually the A and A and immunoglobulins are the main thing. I usually will just send thyroid studies just because that can cause low platelets and the what else to resend. - And we're talking about total immunoglobulins or? - Yeah, just the subsets, just the IGA, IgG, not E, but IgG, IgM, just looking for the occasional patient that has severe combined immune deficiency, which happens every once in a while. So it is important to send it. And that's about it. Those are the main things that we send. - And we say thyroid labs, are you just doing TSH or are you doing TSH? - Just the TSH. - Yeah, just the TSH. And the other thing that I usually send is a direct anti-global test at Acoum's, just to make sure they don't have also another cell line that has immune immunity against it. So like an Evan syndrome, which is when you have immune destruction of two cell lines. - Great. And you mentioned that sort of a virus proceeding or sort of an infectious trigger proceeding, a QITP's comment, do you ever find that it's useful to sort of send up any kind of infectious workup, or is that not usually useful sort of for a first visit and clinic? - We don't usually do it for the first visit because they're usually well. By the time we see them actually, it's usually a week or two before, for the ones that do have low platelets and they're still sick, then we would probably send, you know, looking for EBV, Epstein-Barr virus, that kind of thing, something that could cause a lot of negative even to make the platelets slow, that kind of thing. - So let me just see, let's just kind of summarize this for a second and then we just have a follow-up question. So it sounds like we'll just say, you know, the platelets are 10 for really well-appearing child and your end-hide virus two weeks ago, and you're like, "This is probably ITP." You said you were gonna send an A&A immunoglobulins in thyroid studies. For the A&A, I am probably not on them. - Oh, gotcha, 'cause you feel like that one's so slam dunk. - Yeah. - So say you didn't have a viral trigger that was clear for you, but you're looking for that other trigger. So say everything else of that case is the same. The A&A, what are you looking for on the A&A from that category? 'Cause I don't know of any like specific answer, nuclear antigen that has, you know, is an anti-ITP one. - So the, excuse me, the rate of positive A&A and ITP is something like 35, 40%, it's actually very high. And those kids are the kids that are at risk for going on to develop lupus. So it's good to find that up front and then we can refer them to our rheumatology colleagues to get a workup from them as well. 'Cause ITP can be the first sign of lupus. And it can happen, I've seen it happen, you know, a year before they develop lupus. So it can really take a while. So that's the reason for the A&A good looking for kids who are at risk for developing lupus. And that's typically in the teenagers. So not necessarily the school age kids. - Any other trigger tests that you might send? - We always get a smear, a peripheral blood smear to look at it in the microscope. It's really important to look at the white cells, make sure they're all looking completely normal unless there's activated limbs looking like a viral infection. I always look at the red cells because red cells are important. And then I look at the platelets. The platelets in ITP are usually absent and the ones that are there often really big 'cause they're young platelets being thrown out of the marrow. So looking for those typical findings. If the platelets were all uniformly large and it didn't have that picture of looking like, "ITP platelets," which are either absent or huge, then that would make me think maybe there's an inherited platelet problem going on here. But I always look at the smear before doing anything and any kind of treatment. - So let me just summarize just to see, if we have a case of ITP where we presume to be ITP, it sounds like there's no diagnostic test to say this is automatically ITP. Instead, it sounds like if you have a clear trigger and we'll kind of go through those in a second, then you can kind of let that relax. But if not, you're certainly getting an A&A for an associational lupus. Immunoglobulins associated with any sort of immunodeficiency, a peripheral smear to really look at those and also see the other lines as well as a TSH, T3, T4, whatever you reflex it to to see if you have thyroid disease. Is that an appropriate summary? - Yeah, I think that's about it. And there's a reason behind doing all these tests upfront because one of the treatments, and we'll maybe talk about treatments at some point, is to give immuneoglobulins. And so you can't do a lot of these tests after you'd give immuneoglobulins because they're nullified by the immuneoglobulins. (upbeat music) - Do you feel like you can never get ahead of charting? Imagine a world where you don't need to think about notes again. Introducing free, an AI medical scribe built to free clinicians everywhere. It listens, transcribes, and writes instant clinical notes for you in your style. Freed can be used across all specialties for in-office as well as virtual visits and it works in multiple languages. Written in your style and writing the moment the visit is over, all you have to do is copy it into your EHR. Freed is hippocompli and only takes seconds to learn. Over 15,000 clinicians, including doctors, APPs, therapists, use free to save up to two hours every day and free themselves from documentation. Just imagine the great feeling of coming home without any notes hanging over your head. Get back to doing what you love and let free do the rest. Start your free trial today, no credit card needed. Use code Curb50 to get $50 off your first month when you subscribe. Let's code Curb50 to get $50 off your first month when you subscribe. CURB50 to get $50 off your first month when you subscribe. (upbeat music) What are your classic triggers for ITP? I have to admit, I'm not a person so focused on triggers, but typically there's some story of a viral syndrome in the last week or two. The other thing that we see is actually post the MMR vaccine. I've seen that a few times. And then the most reason thing too, which is alarming is the COVID vaccine ITP or this TTP actually, which fortunately we didn't see too much of. And as far as other triggers, we don't actually know what causes ITP. So we don't have a good answer for that. It would be great if we could say, check this box for ITP and check this box for not ITP, but we don't know what to label that box. Out of curiosity, so for those children who do have ITP that is possibly triggered by either COVID vaccination or MMR vaccination, how do you cancel them about future vaccines? - That is a great question. That's been studied. We don't generally like them to get that vaccine while they're getting in the midst of ITP. So we're usually talking about a year of not getting it. But then after the ITP is gone, if it goes away, kids are actually not at risk for getting it again if they get the MMR again. And the COVID vaccine is very interesting because the, there was actually a study during COVID showing that the risk of getting a platelet reaction. So having thermosetopenia from the COVID vaccine, it doesn't depend on what happened to you the first time. So if you had decreased the first time, you may not have a decrease the next time and vice versa. So you can imagine that makes it difficult to counsel patients on what to do because we're basically saying it's a toss up. We don't, you know, we can't predict. We do know that for that specific instance, getting COVID was much worse than getting the vaccine. So we were recommending that was the party line to recommend getting the COVID vaccines for people with ITP. Speaking of things that we give to patients that may cause thermoside epineia, are drug induced thermoside epineas within the realm of ITP or are they considered something separate? Oh, that's a great question. So drug induced thermoside epineas can be, can be immune mediated. So there are some drugs that cause an immune reaction, which can be, it can be a, I'm blanking on the word, when the new, when a new epitope is formed with the drug and the platelet and causes the antibody to bind there, it can be that, that response. And those are interesting because you can actually test for them if you send the platelets to a place that can test for it. And the New York Blood Center does that in New York. I don't know where else people send up their testing, but they can test for the antibody binding in the presence of the drug. So it's a very, so it's a, and then it gives you a very clean answer of what's going on with, with the drug and the platelets of the person. So are there common drugs that we need to worry about or is it just, it can be anything. Common drugs are antibiotics and anti-epilepsy drugs, especially the Valbrok acid can do that. I've seen that a few times and yeah, that's someone that we see most actually as far as having a definite immune attack upon the platelets. That makes sense. It lines up pretty well with also our other disease processes that are caused by my drugs. Yeah. And I assume once we discontinue drugs, it would help treat the cause, but also maybe we would never give those drugs again because of the same issue. Yeah, you would have a record essence of it. Usually when you stop the drug, it stops within a couple of half-lifes of the drug because the antibody won't bind the platelets without the drug present. So it's a very quick turnaround. I think we've been teasing treatment for a little bit. Chris, kind of into it right now. Jennifer, if you want to kind of read the rest of our case so we can kind of start talking about treatment. Yeah. So getting back to Violet. So Violet's PCP orders a repeat CBC. And the CBC again demonstrates isolated thrombocytopenia this time of 6000. She remains well appearing and has no active bleeding symptoms. So how would you sort of start to think about an initial management approach for acute ITP? That's a great presentation and a great case. So my acute ITP, light bulb is brighter now going off and my inherited thrombocytopenia, light bulb is getting dimmer. The treatment really depends on what the patient looks like, meaning are they really bleeding a lot? If the patient is looking well and has a few bruises and a few particular and does not have any bleeding from nosebleeds or bleeding in the mouth with wet purplera, which are those blood blisters that develop in the mouth, then that person doesn't really need to be treated. They can just be observed. And their course is most likely going to be a very easy one. The kids that come in who have just covered with PTKM bruises from head to toe, I think the official number is 100, if you have more than 100 PTKM, then you're at a treating level. I personally don't count them, but if they're covered from head to toe, that's got to be 100 at least. And it's usually binary. They're usually either covered with PTKM or not covered with PTKM. So it's usually an easy choice. And if they have, especially if they have wet purplera in the mouth, so the blood blisters that happen in the mouth, then those would be in the category that would need to be treated in my opinion. And it's been going around in circles for years, but the first line therapy is recommended to be a course of steroids. And people do different things. They have different regimens, but generally a short course of steroids. And it's something that they can take by mouth at home. It doesn't, doesn't, they don't have to be admitted. And most of the time that will bring their platelet count up in about three days or so. And then follow the current treatment as like a whole subject myself, maybe we'll talk about it a little bit more. The other first line therapy is the immune globulin. And that is that used to be some people's first line therapy over in steroids because it does increase the platelet count faster. And there's some sense in thinking that if somebody is actually bleeding, then you would want to probably do the immune globulin up front because it brings the platelet count up faster. But I would argue somebody's actively bleeding, like having heavy menstrual bleeding or a lot of nose bleeds that you probably want to give both the immune globulin and the steroid, you know, a much higher dose of the steroid together at the same time to decrease the bleeding. But for a violet, probably if she had lots of bruises in particular and some wet proper, she would go home with a short course of steroids. I was wondering if you did in a very brief way. And I don't know if this is possible. But kind of take us through just a little bit of the data between steroids and IVIG because it's bounced back and forth just in the last seven years since I've graduated medical school. And I just want to have just a kind of a broad strokes understanding of what is the durability. Is it immediacy? You know, kind of what's the what's the thing? To be honest, it's more instead of bouncing back and forth, I think of it more as a wearing blinder of platelets and IVIG and steroids. And a lot of it depends on who you trained with where you trained. There's really not a lot of hard data on one being more efficacious than the other. There was some, I don't know where it was from, but some evidence which wasn't which was all retrospective on giving IVIG first made them more likely to have chronic disease, which is I don't think is the case. I think if it's a selection bias. So it's there's not a lot of hard data out there's no there's no study to answer that question of definitively. The real treatment choices whether you want to bring those platelets up today or tomorrow morning or do you want to bring them up in three or four days at home. And it depends on how the person is looking if the person is looking like violet who seems to be doing okay. And I think she's not having a lot of bruising and bleeding. Then she somebody who could go home with just the oral steroid course and then follow up in a few days after the platelet should have come up a bit. But if it's somebody who came in who was covered with bruises and particular and had wet proper in the mouth. You might consider doing the immunoglobulin for that person depending on their activity level and depending on sort of what what their home situation was etc. When you say send them home with corticosteroids can you describe exactly what that regiment might look like sure it would be my my go to regiment is two milligrams for kilogram per day divided twice the BID. And I usually do five days and that usually dumps them up enough actually plenty over the course of the next few weeks. And sometimes we'll get them all the way through their it course and sometimes you would need to treat them again potentially. But if they respond to that then typically they're going to do well. When you say that you may need to retreat them how often are you following labs on them and is it just mostly a CBC that you're following. So for sort of the more straightforward kids with it. I'll start off weekly unless they're really bleeding a lot if they're not bleeding a lot like violet I would say that she could probably come back to clinic in a week. And we would check her we would check the play it's again and then I would probably follow her for two more weeks and if she is doing fine and stable then I would go for two weeks and that just continues. And what I tell the families and what I've what I've experienced is that the all the treatments that we give them that it doesn't modify the disease is it's not a cure. It's just stopping the symptoms long enough for the disease to go away by on its own long long enough for it to burn itself out. So you say that we're only sort of helping with symptoms and so previously you said that a viable strategy is also just observation and treatment correct. So is that follow up the same are you following them with CBC. every week to monitor, make sure they're improving. And then I guess then I have one more question after that actually. Yeah, if the playlets are low, but they're not having a lot of bleeding, I will definitely want to follow them until their platelets are clearly showing signs of going up, which would mean up over 20,000 would make me, it would make me very happy. So it's usually going to be weekly for a few weeks until they start to recover and just go from there again, spacing out, not I spaced out a little timidly. And also I would have them go, they could go to their BD nutrition in two weeks and then come back to me in a month, like that kind of thing. And just kind of spread it out. I know if I was a parent and I had a child with the spruising and possibly a little bit bleeding, but then you felt like they were doing probably well enough that they just needed observation. What does that discussion look like with a parent? Do you have a server spiel or a script that you talked to them to educate the family? This is what ITP is and this is the expected course? Yes, I do. Would you like me to reiterate that? I would love to hear it. So my first goal is to reassure the families, especially once I've seen this mirror, reassure the families that their child does not have leukemia because that's probably what everybody has told them from the PD nutrition to the emergency room to the taxi driver. And so I just want to reassure them that it's not leukemia, their child doesn't have that. And that usually is very helpful because that's usually what they're thinking. And then I talked to them about the platelets, what the platelets are sort of how they function a little bit. And what happens if they're low and how low they have to be for that to happen and sort of where their child is in that framework for somebody who's platelets are six. That's concerning, more concerning. For somebody who's platelets are 70. They could have surgery, so it's less concerning. So that's we kind of go from there. And then we talk about what immune-thromacidopenia means and what that is, meaning that for some reason the body has decided that the platelets are these platelets, those tiny little cells are foreign objects and they need to be attacked and killed. And so they make the bodies, making antibodies against those platelets to kill them. And so what we need to do is to find some way to either if needed stop that process from happening. Or if it's not too severe, just wait it out and it will usually go away in a few months. That's kind of where where I go with that. And just a follow-up question about first-line treatment for acute ITP. So you mentioned it's steroids or immunoglobulins and because not a ton of evidence, but generally steroids first. When you say immunoglobulins, do you mean exclusively IVIG or are you putting anti-D in that category as well? I I don't know how much I should say about anti-D because it's I have not had to go to experience with it and so I don't use it that much. So maybe I can just leave it at that. It's not my go-to. The immunoglobulin that we use is in fact IVIG and not the the anti-D it's the it's the it's the big dose of IVIG and I use the higher dose, the one gram per kilo and the one gram per kilogram on day one and then again on day two if necessary. And the reason for using the big dose is because there's in all that big bottle of IVIG, there's a tiny fraction that has the right glycosolation pattern that actually stops the immune process that's causing the these cells to make all those antibodies. And so you have to give enough of it to to make that happen. And so one IVIG does many different things. One thing that it does is it turns off the dendritic cells and resets the immune system basically and you have to give enough of it to to make that happen. So the more IVIG you give the worst side effects you have and the steroids given at the same time can actually help the side effects but it's it's a lot it can be difficult for the kids to to take the IVIG at that dose. That was going to be my next question is you know we're talking about first-line treatments as corticosteroids or IVIG right now. At what point what if they're not responding to which one you chose like would you maybe start IVIG? Well say they were going home on corticosteroids they seem to be getting worse would you then bring them into IVIG or even if they're if they're in you start IVIG inpatient and they don't seem to respond would you start corticosteroids? You are practically a hematologist now. So that's that is that's pretty much what happens. So if the corticosteroid doesn't work in a few days to you know five to six days when we check again then and the count is going down or they're having bleeding then they're going to get immune globulin and typically I would give them you in globulin with a big dose of methylbridness alone IV at the same time because if they didn't if they didn't respond to that steroid dose they're probably not going to respond to any continued low dose to lowish dose of steroids they're going to need a real slug of it to have any effect and typically the immune globulin and the methylbridness alone work pretty well together and the methylbridness alone can help mitigate some of the symptoms from the immune globulin to the headaches and the nausea vomiting. Summers here, more sun, more light, more time to do all the things that make summer so special. And the number one thing you don't want to be doing all summer? We're here in the hospital. 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All the meals are nutritious, delicious and ready to go. Enjoy more of the summer. Get Factor if you want all the flavor and none of the fuss. So, crib sideers listeners, get started at FactorMills.com/CribSiders50Off and use code crib sideers50Off to get 50% off plus reshipping on your first box. That's code crib sideers50off at FactorMills.com/CribSiders50Off for 50% off plus reshipping. FactorMills.com/CribSiders50Off. Are there any second line treatments then? You start looking at if they fail both steroids and IVIG or is that all we have available? Wow, that's a loaded question. There are several things that are in the second line category. Interestingly, the things that have moved up the ladder on the second line categories are the thromopolarthrin receptor agonis and there are two that are approved in pediatrics. If they don't respond to the glubulin and steroids, we'll probably do it again. Maybe a couple of times to really convince ourselves that it's not working. Then we may have to go to, depending on their symptoms, we may have to go to second line therapies. Second line therapies would be in pediatrics anyway, it would be the thromopolarthrin receptor agonis. My other second line therapy is actually retoximab, the anti-CD-20 antibody, but I typically will go to the receptor agonis first at this point in time because they have such a good track record. I have a couple follow-up questions regarding that. The first is how, essentially, trying to frame it in what doesn't mean to fail. We said, for example, if there was an outpatient, we would give a five-day course of cortical steroids. By the way, I presume it's prednisone when you're referring to one-megapirchig BID, but we would give that. Second, two-megapirchig daily. One big-megapirchig BID, you're correct. I'm sorry. Yeah, my fault. But when you're, I assume, you get a little bit of response next week. Now it's low again. We do it again. How many times would you do that in a row before you would consider it failure? That is a good question. Some of the depends on how bad the failure is. If they come off of the first course of the prednisone with low platelets, but don't bleed, then I wouldn't consider that a failure. I wouldn't be too unhappy with that and we're just going to watch them and see what they do clinically. they just tank their platelets and start bleeding, despite the steroids, then it's unlikely they're going to respond to another course of it. And then we would probably switch to the immune globulin and methylpred. But I think the kids will show us what works for them and what is not working for them pretty rapidly. It's pretty easy to tell. If the patient has a great response to the immune globulin and the high-dose methylprednis alone, but it lasts for two weeks, which happens sometimes, I would try it again, because maybe the next time it will last for four weeks. And we just have to kind of make up the schedule as we go along, depending on how they respond. And so just take the bleeding patient for a second. We all got to know what happens when you give them platelets. What happens when you give them platelets? All of the doctors and nurses in the room sigh, give them a high relief. They're getting platelets. That's the main thing that happens. 2,000 people have to give them something. Yes. And that's the main effect, basically. Usually if we give them platelets, we'll do a one-hour post-platelet count. And depending on how that is, it can give us a clue to how severe the destruction is of the platelets. If it's back down to 2 in an hour, then they're going through platelets a lot. If it's 10 or if it's 15, then maybe it's helping a little bit. And their disease is not so forceful. So that can give us some information, definitely. If somebody is bleeding, so if somebody comes in with heavy menstrual bleeding, or somebody comes in and bleeding a lot from the nose having hour long nose leads, those patients really should consider getting platelets. I got along with immune glibulant and methylpidness alone throwing the kitchen sink at them to really try and get the bleeding to stop. Yeah. And then for hemoglobin's low, they get red cells too, right? They just get everything. Yeah, yeah, get everything. So we've been talking about acute ITP, which is what violet has. I was wondering, when is the cutoff when you would start to call ITP chronic? So the current classifications are a new onset ITP for the first three months. And that's because a fair amount of kids will resolve within three months. A lot of them will come in either they get treatment or not. And either way, their platelets just go absolutely over the next couple of months, and they kind of sail through. The next category is the persistent, which is kind of the midway between acute and chronic. And that's from three months to a year. And it used to be only up to six months, but there are some patients who will spontaneously resolve within a year. And so they kind of want to scrape those patients out of the chronic barrel and put them into the persistent barrel. I think it's a really good idea because I've had several patients who have done great, and they resolve their platelets. And then they come back at 10 months, and their platelets are six again. And so I don't really let them out of my sight until a year has gone up. Even the ones that resolve really well, I make them go back to their pediatrician, at least, at least at six months in a year, to make sure all the platelets are OK. But I think those are good kind of a guideposts to judge. And then the chronic ITP is when it lasts for more than a year. Awesome. Let's talk about treatment options a little bit for chronic ITP. How does that change? I imagine giving a year's worth of corticosteroids is probably not recommended. Yeah, that would be a disaster. That used to be the only thing we could do, though. And poor kids would get so much steroids. It was really awful. But now we have so many second and third-line options that really can work in a lot of cases. It's actually a golden era of ITP treatment. So where should we start? Yeah, exactly. Where do you want to start? So I think sort of the huge windfall for ITP was the thromboportom receptor agonist. And there's three on the market. Now only two of them are approved for pediatrics, though. And I think there's another one coming on the market soon. They work by stimulating the-- sorry, thromboportom receptor on the mega-caricides, which are the big cells that make the platelets. And that thromboportom receptor makes the mega-caricides mature. And it makes them make all their platelets. And so the interesting thing about ITP, the immune thromocyteapenia, is that it's also the combination of a destruction of the platelets, the platelets could destroyed. But there's also a decreased production of platelets. And that is a huge part of the ITP problem. And the reason for that is that the antibodies go into the bone marrow and kill the mega-caricides before they can make platelets. And so if you look at the bone marrow, there's a lot of mega-caricides that usually increased, but they're not making platelets. And they just don't survive long enough to do that. And in the lab, in my experience, the antibodies from people with ITP prevent the mega-caricides from maturing to the point where they can make platelets. So it's a little bit-- so if you stimulate the mega-caricides with this thromboportom receptor agonist, you can sometimes overcome that production problem and increase the platelet count in that way. And it doesn't work all the time, but it works a lot of the time. One question I have is, with these patients who have chronic ITP, I assume there are other complications that we need to worry about. Obviously, ITP itself is a immune type process. So I assume they might be immunosuppressed and then if they're on chronic steroids and they're also more immunosuppressed. So I think if I assume infections would be one thing we worry about, are there other types of issues, whether it's renal impairment or other things that we need to be worried about as the pediatrician for these patients who might be dealing with longer-term ITP? The long-term effects of ITP are definitely partly due to the steroid. That is becoming less as we have more and more second and third-line therapies and more than are available to children. So we don't use as much steroids as we use to anymore. So that's a good thing. So that really helps the immune system. But some of the other medicines that we use for people who with refractory or who don't respond to the first and second-line drugs are immune suppression. Everything else is immune suppression, basically. So those patients aren't going to be at some risk of viral infections. They're going to be at some risk of just getting the common cold or having pneumonia, that kind of thing. More than the usual person. The other thing that can happen is that they cannot get live vaccines because of the medicines that they get. And so they can get behind on their immunizations like that. So that can be a problem as well. Yep. And then along those lines that Chris was asking, the thrumbo-poetan receptor agonist, what are the side effects of those medicines specifically? Fortunately, those medicines don't have too many side effects. The main side effect of that we see is headache. Some people get headaches from it. I haven't seen anything really severe, but some people do report headaches. I've seen the only severe severe headaches that I see is from the IVIG. The IVIG can give you horrible headaches. I had one patient actually get aceptic meningitis, which with increased intracranial pressure from the IVIG, which is rare, but it does happen unfortunately. So it can have a lot of side effects. But the thrumbo-poetan receptor agonist, the two that are available, one is an oral medicine. It comes in liquid or pill. And the other is an injection, which does sting to get. So that's not a lot of fun. And it requires a weekly visit to the clinic, but they both have-- that it feels like a good effect on the ITP. And they will often work if the other one doesn't work. So they're not the same medicine. They work differently. And who are the patients with chronic ITP who end up needing splinectomies? Are they the patients that have just failed? Absolutely, every therapy. It would be hard to give someone absolutely every therapy. There's just not enough time. But the-- so the second line therapies are the thrumbo-poetanachines, and usually the retoxamab. And then the third line therapies are the more classic immune-suppressive drugs. Like, micro-familate. I don't know the-- I don't know the generic name of it, but one thing I use is serolimus. that is it. good one for immunosyopenia and other things that also are similarly immunosuppressive. So, that's when you're getting into the immunosuppression and might want to think about putting them on penicillin prophylaxis. We typically try to avoid having to spleen out in kids. It is, you know, safe fish, safe fish to give after like five years old or so. Some people do after two, but we really try and save the spleen in the kids. The adult providers tend to have the splinectomy in their second-line tier. So, they're often that thing out soon as soon as they don't respond to therapy, which is changing a little now with the thermoportum receptor agonist. So, this spleen for me is generally after a year of trying different therapies and that usually is plenty of time to go through a lot of them. The other third and fourth-line therapies that I've used that have worked are even chemotherapy agents like Vincristine. I've used a couple times, more than a couple times, and it's actually worked. And I've also used anti-plasma cell agents. And there's certainly off-label, but the portus and the anti-plasma cell, the multiple myeloma drugs have actually worked. Super refractory ITP. Would you be able to tell us a little bit about either your experience or what the research shows how racial and socioeconomic disparities affect children with ITP? I've had the privilege of working at a hospital in the Riches Zip Code in the country. And now I have the privilege of working at a hospital in the poorest Zip Code in the country, all within a few miles of each other in New York, which is, which I won't say anything more about. Personally, I haven't noticed a lot of change in treatment of ITP here, but I've also been very active in really bringing the guidelines of treatment for ITP to the emergency room to our clinic practice and really trying to educate people on platelet disorder as an ITP, doing grand rounds, reaching out to the pediatricians, that kind of thing. I think, like everything else, I think that there are probably people that are not getting to us because they're not just not going to the doctor. And that's certainly something that we see, people who have had bruising bleeding for the past six months and didn't come in or didn't weren't able to or didn't think to. So that's a little different than some of the other places that I've worked in New York City. So I think health literacy is really a big issue, which is not on the patients, it's on us. And I think that outreach has helped a bit, because once I started scratching for ITP, it started coming out of the woodwork. There are patients coming in with platelet disorders and ITP and the numbers really increased over the last few years that I've been here and been really trying to get the message out about platelets. So I think there is a disparity and I think I can be mitigated somewhat by education and outreach. Perfect, thanks. And sort of direct things up, this has been a fantastic conversation about ITP. I was wondering, from your perspective, what are the big key take-home points that you would want sort of a general audience to remember about ITP? I think the main thing to remember about ITP is that most of the time in children is going to go away. It's not always the case with the adolescents, but even then it's much more likely to go away than in the adult patients. So especially with school-aged kids that most of the time is going to go away. The other thing that I would love to share with the pediatricians and the people in emergency rooms is that don't tell the families that the child has leukemia and tell their intestines. They have the child has leukemia and leave that to the hematologist to do or not. Because that's one of the most stressful things about the whole episode is that the parents feel and are told that the kid probably has leukemia. So that's a really stressful thing. That's another take-home point. The other take-home point I would have is that Play-Late Biology is really fun and great to learn about and study and practice and we really need more Play-Late Biologists to come up and take my place as I grow old and retire. So I'm putting out a plug for more people interested in Play-Late Biology. Awesome. Well, thank you so much for spending the time with us today. I definitely learned a whole bunch and I'm very sure our listeners did too. Thank you so much. You're so welcome. Thank you for having me. This has been another episode of The Crib Siders. Get show notes and sign up for a weekly knowledge food formula feeds newsletter on our website at www.thecribsiders.com. We're committed providing you with high-value practice changing knowledge. And to do that, we need your feedback. So please subscribe, rate, review the show and Apple podcasts or contact us at [email protected]. Special thanks to our producer for the episode, Jennifer Chisholm, and our wonderful social media team on Twitter and Instagram. I can say amazing. And I've been Jennifer Chisholm. And this has been Chris the Chey-Manchey. Thank you and good night. And by the way, The Crib Siders is for the kids! For the kids!