Pediatric hematologist-oncologist Tiffany Lucas, MD, formerly a pediatrician, knows that primary care visits for bleeding issues are common, with signs ranging from frequent nosebleeds to low energy. She describes how thinking about the normal steps of hemostasis can facilitate assessment, then offers questions to ask and keys to the physical exam. She also explains what PCPs and patients can expect from UCSF bleeding disorder referrals.
nice to actually meet everyone. I'm Tiffany. I'm one of the pediatric hematologist oncologists here. I'm also the fellowship program director. Um And so um love educating. Um Today I'm focusing on my time on the first steps in the evaluation of a bleeding patient, talking about how I think about a patient that comes to my office that's bleeding. Um And I'm happy to answer any questions. I'm hopeful that, but this won't take the full amount of time. So um if any questions or patient related questions, I'm happy to answer them. Why is this relevant to you all? Um I spent three years as a general pediatrician and so you know that you have to keep a pulse on everything. Um But in this particular realm I feel like it we have a lot of crosstalk bleeding super common. Um It can be unfortunately both normal and abnormal, which means you never really know when there is a red flag, it can be congenital. Um And there are some bleeding things that can be acquired later on in life. And so we don't really have an idea of when it might start. Um And um part of the reason that I chose this topic is because this is one of the things that I'm referred most commonly. Um Really the two situations that I feel like I I kind of crosstalk with this is um a patient that comes into me that has a history of Everest axis and the patient that comes to me with iron deficiency anemia, a referral to me. Um usually if there's not a clear dietary cause I find myself thinking about bleeding and prompting a bleeding work up um for patients that have iron deficiency that aren't kind of in the typical toddler drinking 24 oz of milk or 32 oz of milk range. Um so hopefully this is it does feel relevant to you and um we'll jump right in. So I think the best way for me to set this up is to talk about how I think about bleeding as a pediatric hematologist, because it helps frame what I evaluate and what questions I ask and what you could do with your patients prior to them to come coming to see me um to to get them closer to a diagnosis and um getting them an answer that they need. So when I think about bleeding, the first thing I think about is what normally happens or what needs to be working correctly for you to stop bleeding because all of these problems, problems with bleeding, it's a problem in one of these steps that I'm going to talk about. Um and so the blood blood vessels and blood is kind of an amazing thing and that's why I'm in hematology obviously, um it it flows and brings everything that you need to to various parts of the body, but if there's a situation where there's a blood vessel broken, it stops bleeding, but it doesn't clot your whole blood. You only clot at that one spot. Um and so there's a complex system that makes that happen. So one thing that needs to happen normally is um step one basically in a normal situation you have to have exposure of collagen and tissue factor whenever you break a blood vessel or then diphtheria lining. And so um that needs to happen normally if you're gonna have normal homeostasis and we'll talk about the problems with these. The second step that needs to happen normally so that you won't have excessive bleeding is that collagen I think you can see my pointer. The collagen that's exposed from the endothelial lining needs to recruit tissue factor and Von Willow brands which is here in these little black bars um to activate platelets and plug the opening. So I tell patients it's like when you have a hole in the wall, you need to immediately fill the wall first with something and we usually use plaster um or kind of a piece of drywall and that's what's happening first. The glue which is the von Hildebrand holding the platelet plug together. Um So that's step two. That needs to happen normally if you're gonna not have excessive bleeding. And then the other way that you protect yourself from having excessive bleeding is step three, which happens after step to um in step three, you form a fibrous clot. Um I think of it like a mesh um that you put over the top of your drywall that you put up. Um So the activated platelets services surface for this vibrant clot to form. And the vibrant clot is a mesh of proteins um that's cross linked. And those proteins are kind of familiar to you guys from your medical school days. Um All the coagulation factors of those types of protein. And then um the fourth thing that you need to do um to make sure that you don't have excessive bleeding is you have to have a controlled process to trim the ends of the clot. So you made this clot on top of your activated platelets and you have these little things actually in your body. You have T. P. A. Which you may have heard of being used for stroke prevention, you have T. P. A. That naturally occurs in your body to slowly trim off the ends of the clot because you don't want to clot off all your blood. So if you can imagine if your clotting um and you're doing a lot more trimming than you're supposed to. Um So if you have a deficiency in any of these things then you can actually end up having bleeding. So what causes pathologic bleeding? I talked about these are the things that need to happen normally or correctly for you to be able to not bleed all over the place. Um And um basically if you have a problem in any of these four steps then you can have pathologic bleeding. And so what are some examples of problems with Step one? So step one is when um you expose your collagen and tissue factor with your endothelial lining. Um One of these is trauma, which is the most common reason for episode axis. So if you have a kid that picks his nose constantly for whatever reason, um and you have repetitive trauma to your, the inside of your Neri's, you're going to have repetitive bleeding. Um And this can be true after a surgery, for example, um if there's a tonsillectomy where there's an artery cut or I'm not enough of the vessels in the local bed cauterized, then you can have excessive bleeding and I know that seems silly to think about, but sometimes the most obvious reason is the reason that the patient comes in with bleeding. Um you can also have underlying vascular malformations and anomalies that make it um so that your tissue factors exposed more commonly, college and vascular disease such as airlines Danlos. So if you have a, let's say, a teenager who um maybe is very highly successful in ballet or gymnastics because they're hyper flexible, you might want to think about. Um and they have heavy menstrual periods. Um Oftentimes their diagnosis is that being a collagen vascular disease, which has given them success in other realms of their life that might cause them to have easy bruising or bleeding and then other causes of increased exposure of tissue factor are hormonal causes like maharaja often is related to this. Um If they have no other pathologic bleeding, they might have maharajah because of a hormonal imbalance that causes them to build up and shed the lining of their uterus a frequent or prolonged amount of time. So those are some problems that can happen with Step one. These are often overlooked, but I'm often asking myself these questions or the patient, these questions about what predisposing things might have caused their bleeding when they come in to see me. And then let's get into the meat of the pathologic bleeding that you guys probably think more commonly about. Um if you have problems in step two or step three, you can have a named bleeding disorder or something that predisposes you to bleeding. So what are some problems with step 2? Let's remind ourselves what step two does in step to the exposed collagen, which is represented by this blue stuff on the bottom, recruits von will brand, which is a protein that acts as a glue um for your platelets to kind of scaffold on. Um And so if you have problem in any of those things, then you have a name gambling disorder. So you can have a lack of or dysfunctional or less than normal amount of on gillibrand's again, that glue that I talked about. Um If you have it, if you don't have it um at all, then you have type three. Von gillibrand's, which is very severe, you don't make any of it. Or type one, you just make less of it. Um or if you have von Miller brands but it's dysfunctional and not working. That's Manuela brand, type two. and then you can also have problems with step two if you have a lack of or dysfunction in your platelets. Um and I'm gonna put up a slide next about what medications can cause dysfunction of platelets. There are a number of them. But the most common ones that are readily available to people are aspirin which kids don't take very often. But um. Nsaids which are obviously very available and then people take without a prescription all the time. And so I've definitely had patients come in um that I've had new onset of bleeding or bruising. And it turns out there they're taking ibuprofen, you know three or four times a day for a separate issue or muscular skeletal issue. And it turns out that that's why they're having bleeding. Um Any inherited platelet disorder which I'm not going to go into the details of. Um But that's my job, lots of different ways that I can find out they have an inherited platelet disorder or just a lack of clothes in general thrombosis, Wikipedia. So um here are some medications that affect platelets like I said, it's an aspirin. Aspirin affects platelets for the life span of platelets just 5 to 7 days. And so if they even just take windows um they can have problems a week later. Um obviously quote plato grill and too close to pine. Um, hopefully none of your Children are on these medications, but these are platelet inhibitors that are often used for people that have stents. And then I highlighted in orange, the ones that we don't think about very often, but SSR eyes um often have an effect on platelets that make them um make them dysfunctional and you more increased risk of bruising. Um and oftentimes patients are on accessorize. Um, but they don't let you know where they, they're they're giving them from a different provider. Um and sometimes they don't think of them as their medications. Beta lacked. Um antibiotics have this association as well, alcohol and alcohol overuse. Um, definitely has a strong correlation with a religious function. Um, some over the counter or available supplements. Ginkgo ginseng and saw palmetto will have effects on platelets. And I ask always about any supplements that the patients are on and then this isn't a medication, but patients that have yuri mia or patients that need intermittent hemodialysis um will have a dysfunction of their platelets when they're Buon is high. I just put the slide here and I change the background color. Just so just as a reminder for you guys, there are things that cause low platelets, I'm not going to get into a lot of them um, today or the path of physiology, I'm happy to answer questions, but if you have low platelets and you're going to have a problem with type two as well, there's a number of things that can cause some fluids. So then um we move on to step three. And so as a reminder, step three is when the platelet plug is already there from step two with the von Will Brandt's glue and the platelets. Um But step three is when the fiber in platforms and the fiber in clot again, is this mesh, I think of it like a mesh that plasters over the top of the thing that filled the hole. Um And so there's no co ag talk without co ag cascade. You don't really need to remember what's kind of up front or what's intrinsic or extrinsic. The whole point is that a whole bunch of numbered factors come together and they make this vibrant plot at the bottom. Um And so it's my job to to know what each of these um komag factors do. But the short of it is if you're missing any of these numbered factors, Then it's going to make it difficult for you to form this vibrant clot, which is the problem in step three. Um So uh problems in step three can be described, drainage anemia or low fibrinogen level. If you go back to the slide before fibrinogen is this lasts a little bit that you're making to make the fibrous clots. So if you don't have or you have dysfunctional fibrinogen, this factor one you're gonna have a problem and then low levels of any of the other coagulation factors hemophilia. I put an orange because it's the most common, which can be a lack of factors 89 or 11. And so they're numbered in order ascending A. B. And C. Selector. Uh No factor eight or a low factor eight is hemophilia A no factor or nine is hemophilia B. And no factor 11 or low factor 11 is hemophilia C. Which is not excellent. Um But in K deficiency or being on the medication warfarin um decreases your level of coagulation factors. And so you also have a problem with Step three direct thrombin inhibitors. Um you might have heard about dough acts, which are more commonly used in adults, but recently have been approved for treatment of venus Rambo embolism and kids. Um These are direct inhibitors of thrombin um which is what is being generated when you make the vibrant clot. Um And so being on that medication is gonna decrease your level of coagulation factors liver disease. Since liver delivers the site of synthesis for most of these coagulation factors and Factor 13 deficiency. Um which if you go back to the side before, once you make the vibrant clot. Um you need to cross link it to make it strong and factor 13 is another factor that does that that can cause delayed bleeding for those of you that potentially ever need to study for boards. Factor 13 deficiency um is something you need to test for when you have a pediatric patient with intracranial hemorrhage post birth. So because it's associated with delayed bleeding and has a high association association with um intracranial bleeding. And one of the signs that you can find when you think about patients that have Um potential factor 13 deficiency is they also have bleeding from their umbilical stump more than five days after birth. Um that can be a sign of factor 13 efficiency as well. So um where is the bleeding? Um So as I talk with the patients get their history and figure out where the bleeding is. It tells me what part of this step, what a part of these steps I need to interrogate. So if there's bleeding where there's trauma um then it's more likely a problem with step one. Um Petechiae or mucosal bleeding, It's much more likely to be a problem with step two. Here's just some photos of wet purpura and the tongue um which is more common with I. D. P. And platelet dysfunction. And um petechiae like on the eyelids. Just again problem with step two and if you have joint or muscle bleeding so large um effusions that are filled with blood in your joints it's more likely a problem with with step three. So um part of what I'm here to talk to you about today is how can you help start the assessment process. Um I think the most important way to assess this and you probably have been able to tell from how I've discussed this before is a good history and physical. Um There are certainly labs and I'm going to talk about soon, but um in order for you to do a history and physical, you have to have an ability to discern what is concerning or what can be concerning and so to make sure to elicit those. Um So the personal history questions that I start out with um wearing my pediatrician hat is really starting from birth. And I kind of think about all the challenges that they might have from birth until whatever age they're presenting um with. Um and oftentimes the first thing that kids come up against if their mail is potential for circumcision. And so how did the circumcision go? Um immunizations like hepatitis B and vitamin K. These are intra muscular injections. How did those go where they're bruising? And was there bruising at the site or Developed a hematoma? Those could be early signs. Like I said, umbilical stump separation can ask me um can tell me some things about whether I should consider factor 13 deficiency. And then one of the questions that I ask often that most patients that come to me have never had asked before is um were there bleeding problems when your teeth came out? So for dental eruption and also teeth tooth loss if they're old enough that they might have lost some teeth already. And then there's taxes often is a more um kind of obvious one that you ask about but um Oftentimes people say, well they've never really had any other reason that they might bleed before. So I don't know if this is the first time they've bled or not, but there are some potential reasons that you can ask in that, in that even a very young child that will help you decide whether you should be a little more concerned if they have any of these previous bleeding. And then um as a pediatrician, we often find ourselves um getting information about patients mostly from their family history. Um and because um the bleeding disorders that I talked about, many of them are congenital. Um It is important to ask about family history of bleeding disorders and I usually say, have you ever heard of the term hemophilia or von Bulow brands are rare enough that I think if anyone's heard of them, then there might be some concerns that there's a family history of them. Most people can't exactly remember which one they are, but that would be a big enough signal that we want to interrogate further. Um The other thing that I asked about that everyone kind of has to go through in a, in a child's family is um whether the mother had maharaja. Um and people might not know that term or heavy periods sometimes can give a lot of false positives. But I usually ask um has did the did the mother ever need a blood transfusion or how she needs to be on iron her whole life because of heavy menstrual periods? Or did anyone in the family end up getting a hysterectomy because they bled so much. That's another kind of signal or red flag. Um And so most people will know the answer to that and whether or not there's someone that needed a blood transfusion in the family, but they might not know if they have a diagnosis of a bleeding disorder, adult onset or adult onset, but adult um Tempest axis is unusual. And so I always ask about that and then again, blood transfusions required in the family. Most people are aware of blood transfusions but may not know of other things. And then every kid um will uh have the history of how their childbirth, their actual birth went. Um I always ask about postpartum hemorrhage as a signal that can be um concerning as well. And then on the physical exam there are some things that you can look for bruising an unusual pattern. So not just at areas of known trauma. I usually ignore for kids under the age of seven, any bruises that happened from knee below, but if bruises are happening kind of on the buttocks or in the chest then that that would be unusual obviously looking for. I have had a splendid mentally or olympic Ganapathy since bleeding that's kind of acquired or happens later on in life can be associated with malignancy. If you have any kind of infiltrated process in the bone marrow like um a leukemia. And you might be able to see some physical exam findings as well. And then there are some um syndromes that are associated with platelet dysfunction or platelet abnormalities. Um And so they have these concerning additional physical exam findings like Oculus, cutaneous albinism, absent radio and the underside of penny caps and radio I syndrome eczema. For patients that have Wisconsin Aldrich probably remember that triad and then a condition called Jacobson syndrome that's associated with platelet disorder um is associated with developmental delay and facial dysmorphic ISMs. Um But the developmental delay can be mild. Um And so Jacobsen syndrome is probably one of those syndromes that can get picked up later on in life and often gets picked up when they come to me for excessive bleeding. And so then your next steps in evaluation are to think about testing. Um This is my first line list of testing. Um I always get a cbc with differential including platelet count. Um Sorry sometimes I just say that because sometimes um some labs don't do platelets with cbc. Um fibrinogen also known as fibrinogen activity in case your lab asked for differently but that would be a test that looks for low fibrinogen or vibrant again, activity abnormalities. Um the PT and PTT and then usually um if you're talking to a patient that might be bleeding, not only do you want to know whether they have a bleeding disorder or start that process before they get sent to me. But um usually want to know how much have they been bleeding and so often times I find myself um sending an iron panel and arithmetic as well as an iron panel and a ferret in because you're worried about iron deficiency anemia. Um So if you're gonna be poking the kid to try to figure out why you also want to make sure that they are not um losing so much blood that they're having iron deficiency anemia and that those labs will help you with that. And then the next steps of evaluation kind of the second line test would be considering, especially if there's a family history of bleeding disorders or bleeding that might be concerning to you. The von Hildebrand panel and I just listed on the slide what von Hildebrand panel actually comes with comes with the antigen restaurateur and co factor activity in factor aid activity. Um Sometimes um if you're unlucky you're lab doesn't have the panel available and you remember the names of these things but um usually most places you can just click onto the front panel and kind of order all three at the same time. Um I also put the slide in here just to have it if you look on up to date. Um There are reasonable age specific norms in case the lab doesn't flag them correctly. Um But it's on up to date, so I'm assuming most people have access to be able to have that, but I also copied it here because the age specific norms do change with time and so I think it's important to know that um it's worth it to double check um even if the lab is flagging something that the patient doesn't actually have any significant symptoms and then what do you do next? So you have a patient that has bleeding, they may or may not have a bleeding disorder. You sent the first line testing waiting for the results to come back um when I see them. Um The first thing I do is talk about all the things that we're going to have you take care of um while we wait for these lab results. Um and one of them is episode access management. So like I said, one of the most common reasons that I see patients um with with potentially disorders episode axis. And so um I talked about episode IX all the time, making sure that they have a good emollient that they're using for their nose and that they're using it regularly kind of positively reinforcing anyone that's using either aqua for Vaseline in their areas. Um Just talking in general about how to apply pressure correctly um to the nose and not continue to kind of keep checking or putting something in the nose and taking it out commonly to have more trauma counseling against. That is really important. Um Because even if they have a brain disorder, I'm still gonna want them to take care of their their nose bleeds um in the correct way rather than just fixing their underlying brain disorder. Of course we'll do that. But they still need to the supportive care they need for their efforts. Access management. Um If they need it you can give them oral iron replacement while they're waiting to see us. Um and then counseling on how to prevent additional bleeding. So um avoiding insects and aspirin is probably the most common way that we tell all patients. Um while we're figuring out this work up, why don't you avoid taking ibuprofen or aspirin? Because those are known to affect your ability to stop bleeding and we don't want to add insult to injury basically. And then one of the other things that you can start thinking about that maybe you don't think about often is um are bleeding disorder patients do end up having problems when they need dental care. Um Because if they need a root canal or they need teeth taken out, it becomes really difficult because we need to control their bleeding so that they can get the procedure that they need. Um So I spent a lot of my time reminding kids to brush their teeth twice a day. I feel like a dentist um and floss. Um Because preventing any dental problems will be much higher yield than um than later on needing to deal with fixing their bleeding disorders, they can get their teeth taken out safely. And then I like to tell you a little bit about what happens with us. So when when they come to us, if you're if you suspect a bleeding disorder after kind of going through the exercise that I just went through in your mind um then we can confirm the diagnosis or um do additional testing beyond what I had mentioned there. There's a number of other tests that we have available to us that we consider. Um If the bleeding history is strong enough and even if those tests are all negative will certainly think about other more rare bleeding disorders. So we can get you that diagnosis and then what happens after that is um if they do have a diagnosis of a bleeding disorder, then we see them um in our comprehensive bleeding disorders clinic at that clinic we see patients that have hemophilia von Bulow brands and platelet function abnormalities and some rare um other subtypes of bleeding disorders. Um And a it's a great community for the patients so that they get to know each other and they don't feel like they're the only ones that have to deal with nosebleeds all the time or really heavy periods. Um We have a social worker that's involved in our team um But also it gives them kind of access to us for us to make a bleeding plan for them. Um So usually they have this um in the in the form of a letter. Um We also work with their schools to have an I. E. P. Available or 504 plan if it's just medical. Just to be able to say they might have a nosebleed. This is what you have to do. Um We give them travel letters to make sure that they have the medication they need if if there um any sort of movement is managed by a medication um And and kind of see them on a regular basis and they have a pretty close relationship with us. But the most important thing to for you to know is that it's important for them to come see us because um we can make that bleeding plan for them and if they need to have a dental procedure for example um we can connect with the dental team here at UCSF. Um For them to get the dental work done in the hospital potentially hospitalized if needed. Um with the right supportive care medications they need. Um It's hard to do that until they're kind of plugged into our obliques research clinic. And this is just a slide with the members of our human team. Um You'll see all of our names. Um We recently um are kind of sub specializing a little bit too human ecology and oncology. Um And my name's kind of on the second column here for human biology, also still see some oncology patients. And I just want to remind people how to refer to us. You can um Call the 1877 you see child. Um and if you ever have questions, that access center number can get the hematologist on call to.