Medical Case Study: Riding the Struggle Bus (PDF)

Two. There we go. All right, we're gonna talk today about a case named Sandy. So, for a start, I wasn't here for Doug. Doug's like my favorite case in the world. Doug was a super interesting guy. But this case definitely is a little bit different. In full disclosure, I did not take care of this pati...

Two. There we go. All right, we're gonna talk today about a case named Sandy. So, for a start, I wasn't here for Doug. Doug's like my favorite case in the world. Doug was a super interesting guy. But this case definitely is a little bit different. In full disclosure, I did not take care of this patient the first time that they presented. So I'll give you a little bit about the history of their first episode. But I did help take care of this patient the second time that they presented. So when I come back next week, we will talk about anticoagulation and the anti-platelets. All things blood thinner and we'll go through what makes them different. This is just a little primer. You're not gonna be tested on material from this slide. They'll use some of the slides from this deck in the deck that we'll be using next week when we go through the coagulation cascade. So, we are going to start off with this patient, how they presented initially and kind of understand what the physiology of that disease process is. And then we'll transition to future issues that arose that required this patient to return to seek medical care and how her management at that point was definitely different than the first time around. I'm gonna say I'll talk with you guys about how this patient has affected me and what we can learn from this patient. So, I called this case Riding the Struggle Bus because Sandy Lynn Chris is an 18-year-old female. She's a college freshman. She's a flute player in the marching band. She's not sexually active. She denies alcohol, tobacco, or illicit drugs. Past medical history is significant for dysmenorrhea, so irregular periods as well as acne. These two things combined kind of make me think a little bit of a PCOS picture, which is very common in females reproductive age. Medication, she's on yas, which is a combined oral contraceptive, though she was using it not for contraceptive purposes, but for the dysmenorrhea and the acne. And then travel history. This is really important. She had a five- hour bus trip with the band to go to another college to play in the football game. And so, on that five-hour bus trip, there wasn't a lot of time to get up and stretch her legs, so she's just sitting there, allowing blood to kind of be very stagnant and it's flowed throughout the body. And in case you're wondering where this picture is from, that is not Sandy. That is actually me back in college playing bass drum, but I don't have a picture of Sandy from college, unfortunately, on this side deck, but I absolutely hated carrying this heavy thing around. So, Pangent gets back from her trip. A few days later, she notices some significant swelling. It was swelling of one of her legs, the left lower extremity, very red, very painful, very hot to touch. Very scary. This is someone who is 18. This is their first time being away from family. Their family is three hours away. They're in another city, and they're like, what is going on? And so, they call their parent. Their parent rushes down and gets them to the hospital, and the hospital finds that, when they do an ultrasound of this left leg, that there is a blood clot in the Great Saphathis vein. Now, blood clots are relatively common. I mean, they're not so common that all of us are gonna have one, but they're not so uncommon that we can't predict them. This is a patient who has sat for a long period of time, who's on an oral contraceptive. So, all of those things give you a reason to be able to write off and just say, well, at least we have an explanation for these things. Thankfully, the doctors didn't just write it off, because normally, genetic testing is not indicated the first go around. So, I'm very surprised that they did a genetic workup, but they went ahead and did one, and they found, when they looked at the most, the four most common coagulation disorders, they found that she was negative for the prothrombin gene mutation, so that was good. She was negative for anti-thrombin III deficiency, great. She was negative for protein C activity, awesome. But then, we get to the factor V glidin, I'd say, and factor V glidin shows she has one of two copies that are affected. So, what does this mean, and why is this problematic for this patient, particularly later in life? And so, I wanted to take a step back and talk about how blood clots form in the grand scheme of things. So, there's a guy, his name is Dr. Virchow. This is called Virchow's Triad. Whenever you're, if you go onto a medical school, PA school, pharmacy school, and you start hearing triads and pentads, they're usually really important. So, this is Virchow's Triad as it relates to thrombus formation. The first rung that's necessary for thrombus formation is to have some sort of circulatory stasis. So, if your blood isn't moving very well, most common reasons are gonna be immobility, as well as varicose veins. These are some really good indicators of circulatory stasis. The next is some sort of injury to the endothelial cells. And the reason that this is not necessarily required, but very common, is that this is actually what starts the coagulation cascade. So, any damage to those endothelial cells releases cytokines that initiate the cascade of events that lead to thrombus formation. And then lastly, hypercoagulability is the third one. So, anything over here really starts to tip the scales. So, inherited thromophilia, which is this patient, she was on estrogen, and those sorts of things. And so, the reason that it's so important to recognize this is once the clotting cascade starts, the whole purpose of the clotting cascade is to make a very, very strong fibrin clot. If you were to be stabbed with a knife, would you like for your blood to stop bleeding? Yes, that is a very good goal, and our bodies can try to do that, but that may be a little bit extreme for them. But let's say if you were to put in an IV and take it out, you wouldn't want that IV site just to keep bleeding, right? So, upon exposure and damage, you have this clotting cascade that gets started, and we have various pathways. We have what's called the intrinsic pathway, which is measured by the APTT. We'll go over all of those in great detail next week. We have the extrinsic pathway, which is measured by the PT. And then finally, we have our common pathway, which is measured basically by both of them, the APTT and the PT. Incredibly important, when we start talking about mutations, anything that occurs in this common pathway, that becomes really problematic. And the reason being is regardless of how this cascade starts, whether it's extrinsic or intrinsic, it always has to end with the common pathway. So if your factor five is overly active, well, guess what? You don't require extrinsic activation. You don't require intrinsic activation. Your factor five may automatically start converting factor 10 into factor two, leading to massive clot formation. Now, if you're homozygous for this, that's really bad. Your odds of clots are like 100 to 1,000 fold at the regular population. For this patient, being heterozygous is not nearly as profound, though it is certainly significant. We will memorize the clotting cascade for the purposes of this course. It is an essential part of medical school. We are not gonna memorize this version. This is the whole clotting cascade and all the things that like regulate it and go back and forth. We have a lot of players here, and you'll notice that they kind of like weave back in, in forward feed and do loops. That's way too complex in my mind for anyone to memorize. So what we saw in that previous slide, we're gonna work through how we memorize that diagram. And that diagram will be incredibly important when you guys take your last exam in the course. You'll notice on here though, some key players. So I mentioned a couple things. I mentioned Prothrombin gene mutation. So this is Prothrombin, it's factor two. So if you have a mutation in this, it quickly gets converted into Thrombin 2A, which is basically the last step before clots. Of all of the clotting disorders, Prothrombin gene mutation scares me a lot. I mentioned Antithrombin III deficiency. Antithrombin is basically one of the breaks for this whole thing. So it's nice that all this gets started, but how does our body turn it off? And the answer to that is Antithrombin III. The other answer to that, the other breaks, are protein C and protein S. We also measured that activity, it was normal. If those levels were low, again, we would have way too much clotting going on. But this patient, this is where her deficiency or really her altered mutation is, is in this factor five. So her factor five basically is mutated to always be factor five A, bypassing all the other steps necessary. So anything that crafts 10A will quickly turn it into Thrombin. The other thing complicating this is birth control, specifically estrogen-containing birth control is pro-transcription factors. Estrogen stimulates your body to make various transcription factors, two, seven, 10, 12, 13, and vibranogen. When you're pregnant, you have a lot of estrogen. When you give birth, do you think your body wants you to stop the bleeding that happens afterward? Yeah, so that's why estrogen likely, from a Darwinian standpoint, is pro-transcription factor production. The other downside of this particular one that she was on is the whole idea with this Drospiranone is that it possesses antiandrogenic properties, so anti-testosterone properties. And the reason for that is because it can be really helpful in treating the acne associated with polycystic ovarian syndrome or PCOS. The downside of that is it is also incredibly profound to producing clots. So now we've taken this patient, they've sat for five hours, they're on an estrogen-containing birth control, they're on a Drospiranone-containing birth control that stimulates clot formation, and they have a hypercoagulability disorder. No point, so it's easy to see how all of this starts to add up, and in our patients, we have a lot of factors that are tipping us into forming a thrombus, and that is why she ends up getting a thrombus of her great saphenous vein. Really important when we talk about blood clots. Blood clots can occur in one of two areas. They can either occur in deep veins, or they can occur in superficial veins. Superficial veins are a lot smaller, so they're more prone to clotting, but they're also not as big of a deal if they get clotted off. If you get a blood clot of the deep veins, that is very significant, and you get put on anticoagulation for a long period of time. This patient was very lucky. She had it in her great saphenous vein, which is superficial, so this patient did not have to go on anticoagulants. So she was put on an anti-platelet. She was put on aspirin, and we're going to make sure that we understand the difference between anticoagulants and anti-platelets. You have two types of clots. You have clots that are derived from that clotting cascade and have platelets incorporated into them. Those are gonna be fibrin-rich clots. You also have platelet-rich clots. These are platelets that start the clot, and then recruit some of that clotting cascade into it, but are mostly platelets. So two very different types. In this patient, it was not necessary to anticoagulate her, which is awesome, because anticoagulation trumps anti-platelet activity. Anticoagulation is incredibly risky, really is associated with a lot of bleeds, so you have to be really cautious about who you start, and this patient was able to get away with aspirin, a warm compress, and some Advil to take away some of the pain associated with it. So overall, not that bad. The other thing, discontinue the use of oral contraceptives, specifically the ones that have estrogen in them. So this patient no longer can have any of the combined estrogen-containing products, has to take either the progestin-only pill, a progestin IUD, a progestin implant, which is a progestin that goes into the arm, or the copper IUD. There are other things about this patient's medical history that make this difficult, but for the purposes of where we are now, this is basically this patient's first episode in which he's been treated with. Questions about Sandy so far? Because Sandy's about to get interested. All right. So Sandy, 18, takes this. She's on NSAIDs for about 60 days, and aspirin for about 60 days, completely off of it. Transitions to a progestin-only pill later in life, and things are hunky-dory until she returns about 10 years later, once she's 28. And this, at this point, now, I became involved in Sandy's care. So she was in the band. It makes sense that she's now a music teacher. Past medical history has grown just a little bit, but still has the dysmenorrhea. We have the heterozygous factor five Leiden that we know about. And now she's presenting, and the reason she's here for this visit is for unexplained infertility. PCOS is a very common cause of infertility, so it makes sense that this patient would potentially struggle with infertility later on. And she also had varicose veins. And remember, stasis is a risk factor for blood clots. And so in this patient, she has varicose veins. Blood ends up pooling in those lower extremities, increasing their risk of blood clots. She goes to an infertility specialist who starts her on letrazole with the goal of inducing ovulation, and it was successful. So she's at her doctor today for a positive pregnancy test because there's an EDB baby, oop, oop, too far. EDB baby, right there. We have an implantation. We are good to go. She goes to her OB guy, and her OB guy goes, great, you're pregnant. You need to go to hematology oncology right away. Why do they want her to go to hematology oncology? Does she have cancer? No? What's she worried about? Do what? Yes! So when she had increased estrogen before, granted she was taking it by pill, she got a blood clot. Now she's got increased estrogen now because she's pregnant. And I don't know if you've seen someone who's eight or nine months pregnant, they're not moving very much sometimes and are a little bit immobile. So there are a lot of risk factors that start to go. In addition, we also have this patient who has varicose veins. We have the pregnancy. She's gonna have lab draws all the time. I mean, there are a lot of labs that go when you're pregnant. She's going to go in for the delivery, and that's gonna be certainly a traumatic experience in terms of trauma to the body of the risk of bleeding. And so whenever you have a risk of bleeding, you also have a risk of clotting. So the question then becomes is, what do we do? What do we do in this patient who has nothing wrong with her other than being happy and pregnant and has this genetic disorder that she hasn't had to think about for 10 years? Do we need to treat it? What do you guys think? Do you treat it or do you not? How many people think we treat it? How many people think we don't? Okay, let's talk about the risks. Let's say we don't treat it. What are we worried is gonna happen? She'll get a blood clot, she could be in the leg, it can break off from the leg, travel to the lungs, and then you have what's called a pulmonary embolism or PE, and she could basically suffocate to death and die. Okay, let's talk about blood thinner. What are the risks? Uncontrollable bleeding. She could fall down a flight of stairs. She could be in a small car accident. She could just bump her head on the headboard and pass away from a brain bleed. Weird day for that comment. And we had a colleague who unfortunately passed away from a brain bleed, and that just really hit me in that moment. Blood thinners are very, very dangerous. So it's a very difficult balance to decide what to do in these patients. Honestly, because she was heterozygous, no one really had a strong preference. One doctor said, yes, we're gonna do blood thinners. One doctor said, no, we're not. Another doctor said, yes, we are. And so two out of three said, yes, we're gonna do it. So this patient ultimately was placed on a blood thinner. Yeah, great question. Thank you for setting me up for this slide. So the question was, is does the blood thinner have any effect on the developing fetus? And the answer is really, it depends which one you use. So we have heparin products. This includes things like heparin and low molecular weight heparins. The most common one is anoxaparin. We have some new oral agents, factor 10A inhibitors. You'll notice all these have like an XA in them, Fonda Perinox has an X at the end. Yeah, it's kind of close. So that's our direct factor 10A inhibitors. We have our direct thrombin inhibitors, things like our gatriban and dabigatran. And then we have our tried and true, lovely, old drug, old rat poison, warfarin. All of these oral formulations, Fonda Perinox is not oral, but all of these over here are really convenient for patients to take, right? Pill by mouth. All of these, teratogenic, can lead to fatal birth defects and are all contraindicated in pregnancy. That stinks. So now we're really left with either heparin or anoxaparin. And these are injections that you have to take. Anybody like really scared of needles? Yeah, this patient has a huge phobia of needles. Went to the vet, saw a dog get an injection passed out at the vet. Ever since that moment, has been deathly scared of needles. They are not very thrilled when pharmacy lets them know, hey, here are your options, and they're going to be an injection. So this is definitely a team sport. So the patient's husband was involved in ensuring that the patient would get their medication appropriately. So let's kind of compare and contrast what we have available to us. I mentioned that we have either heparin or anoxaparin. So both of them are going to be administered as subcutaneous injections. So one's not better than the other. Why did they go backwards? I know why. So when we give these injections, most commonly, it's going to be the sides of the abdomen. You can also do it on the tops of the legs and on the backs of the arms, though the abdomen is the most common place. As you begin to grow a fetus in your stomach, the belly stretches and that skin becomes quite taut. So it becomes a little bit more difficult in the later stages of pregnancy, and it's associated with more pain. Really important that you tell people that you are on a blood thinner because I tell you what, this patient looked like they were black and blue all over like they were a domestic abuse victim. And I said it because if you think about those areas that we're talking about, we're talking about the stomach, we're talking about the legs, we're talking about the arms, we're talking about places that are very commonly covered by clothes. So it's very common for patients who are on anticoagulants to actually confuse with someone who may be a victim of abuse because this is not an uncommon bruise. This bruise is most likely just a really bad injection. However, it looks really terrible like someone is punching them and then they're covering it up with clothes. So really important that they be counseled effectively on, hey, this is what's gonna happen. You're going to bruise. It's not a matter if it's a matter of when, and you let them know what are some really dangerous signs of bleeding or bruising. Now here's where things start to divide between these two. One is given every 12 hours, one is given daily. How many people wanna inject themselves twice a day? How many people wanna inject themselves once a day when the other option is twice? Yeah, that one. Okay, so there's an advantage for Noxaparin, right? Now we're starting to see where the scales are starting to tip, okay? Noxaparin sounds a little bit better compared with heparin. As far as how they inhibit factors, both of them inhibit factors two and 10. Though Noxaparin has that XA, it is predominantly a factor 10 inhibitor. That's really neither here nor there in terms of how we clinically choose, though it is here and there when we talk about exam question writing. Though it really doesn't affect our choice. Onset, this is semi-important. One is 20 to 30 minutes of onset, heparins very quick, and Noxaparin has a much slower onset of three to five hours. And that's associated with their half-lives. So heparin's half-life is only two hours, and Noxaparin's is seven hours, which makes sense, right? Shorter half-life, shorter dosing interval. Longer half-life, longer dosing interval. So, why would I not want my patient to be on Noxaparin? Let's go there. Why would I say, you know what? This patient should get heparin over on Noxaparin, specifically a patient who's pregnant. Yeah, if they're close to being in labor, how come? Yep, so if they have a shorter half-life, it's gonna exit the body faster. Absolutely, so as we get closer, one of the considerations is, if you're gonna put an epidural in, one of the risks of epidural placement is a hematoba that can develop around the spinal cord and lead to profound paralysis. Really bad side effect. So it's contraindicated to place an epidural within six to 12 hours of heparin. However, it's contraindicated within 12 to 24 hours of an Noxaparin. I can tell you when my wife was pregnant, her words to me was, I'll be getting an epidural and you're gonna deal with it. And I was like, it don't matter to me, you be comfortable, that's all I really want. I am here as a hand to hold, nothing else. So get whatever epidural you want. So this is the reason why early on in therapy, an Noxaparin is the recommended. So for the first 36 weeks or so, an Noxaparin is preferred. And then after 36 weeks, once we're gearing up towards birth, that third trimester is going to be specifically late and the third trimester is going to be when heparin is preferred. What do you guys think about induction? Should this patient be induced or should they not? So induction means basically stimulating the baby to come as opposed to waiting for the baby to come naturally. Yeah, yeah, the nice thing about induction is you can plan for the bleeding that's about to occur. If you wait for it to happen naturally, you may give the dose of an Noxaparin and then, or heparin and then 10 minutes later, the water break. Oh no. So it's nice to have a defined induction date. So that way you can decide, okay, and in this case we did it at 39 plus one. 39 weeks is the very earliest of what is considered full term. 39 to 42 is full term. The OB-GYN made the decision that at 39 plus one, we were going to induce. And the reason for that was we didn't want to risk going any longer. Any shorter is hard to justify in certain patients, particularly those who have significant adverse effects of pregnancy, talking like preeclampsia, we will start to do deliveries around 36 weeks. But if we can, 39 weeks is definitely preferable. So that's what ended up happening to this patient. Is she was placed on an Noxaparin until week 36 and she was switched to heparin until week 39. Now, after pregnancy and after delivery, once we were sure her bleeding has stopped because postpartum hemorrhage is very significant, she was then placed back on a Noxaparin for the next six weeks because you're also hyper quaggable in that first six weeks postpartum because you also have a lot of hormones that are being released at that period too. So that was kind of her treatment plan. Now I will tell you that this was a lovely plan, 39 plus one. m. The plan was to do induction at 7 p. at night because that's when this patient's OB-GYN would get on service, so that way hopefully she would deliver the next day while the OB-GYN was on. On day 39 plus one, patients water broke at 7 a.m. in the morning, 12 hours early. Good news was heparin was given the night before and so the patient had already been off of heparin for 12 hours, so the risk of bleeding was very limited and this patient was able to get an epidural. Now you guys may remember that Doug Hole, it meant that he died a hole in his head. And this patient, I named Sandy Lynn Chris. And the reason I named this patient Sandy Lynn Chris is because I had to figure out an anagram and this was one of my favorite scenes in the Harry Potter movie and when I was reading the books I was like, oh my God, you're kidding me. Sandy Lynn Chris, if we rearrange her letters, is Lindsay Skinner. This is my wife and my child. So when I say I was involved in this patient's care, I mean, I was involved in this patient's care, okay. You wanna talk about someone who loves injections. She did not give herself a single injection for nine months pregnancy. I gave her all of them. Warning at the end, night all the other times. I also cleaned litter boxes for nine months. In case you don't know, there is a risk of a brain bacteria that you have to worry about during pregnancy that comes from cat ****. Toxoplasmosis, it's actually a fungal infection. So I cleaned all those and I slapped ham sandwiches out of her hand night and day because of the risk of listeria. We laugh, someone, not gonna say who, but they're like, well, I would only eat Boar's Head because it was like a fancy brand. And then Boar's Head had this huge listeria outbreak and she was like, maybe the lunch meat is not a good idea. So that was kind of my role through all this. And then the nice thing was, I'll be honest, if this is why I use this case, this was incredibly terrifying as a healthcare provider. It is absolutely impossible to leave your knowledge at the door when you walk into a doctor's appointment. We're sitting there, they're doing an ultrasound and she has a spot behind the placenta that's bleeding. She has a hematoma that's developed, small little pool. That's got me terrified. You know what that does? That bleeding can grow and cause placental detachment. And then you have intrauterine demise, terrifying. So I am internally freaking out. I'll leave out the other words. But on the surface, I'm having to remain like, I'm just gonna wait till the doctor says what's going on. Just gonna wait till the doctor says what's going on. And the response was, so this is something that could grow or hopeful that it won't, it normally can be reabsorbed by the body, though you are on a blood thinner, we'll just keep watching it. My wife probably forgot about it at that moment. Every ultrasound, I'm sitting here going, how's that hematoma? How big is the hematoma compared to last time? Because I'm wondering if it's gonna be growing or getting smaller. Because I'm literally debating like, do I need to ask the hematologist, do we stop the blood thinner? And now I'm starting to debate, whose life am I saving? Or who am I most concerned about between my wife and my daughter? This is really hard and really scary. My wife, here's middle name is not Grace, but should be, fell down the stairs, all six months pregnant, lost her balance, backwards she went, straight down. You wanna talk about freaking out. I am freaking out. Like I am checking her over, up and down, asking her, did you hit your head? No, did you hit your stomach? No, thankfully she fell backwards, mostly just on her rear. She had a bruise from here, all the way up to here. It looked awful, but thankfully we went, we got checked out, ultrasound, everything was fine. And at the end of this lovely process, my daughter was born after five years of infertility and lots of prayers and lots of crying. And so to add this as one other thing on top of it, and I won't even get into the other issues related to why infertility was such a big deal with my wife. Spoiler, there are anatomical reasons that made it very difficult. And once we've learned those anatomical things, the doctor was like, well getting pregnant is actually really easy with this one. The difficulty is carrying a term, it usually doesn't happen. Okay, so now I'm worried about the risk of preterm labor, in addition to the fact that my wife's on a blood thinner and could then spontaneously bleed out and die at any moment. So that was really great. But everything was fine. This is my daughter when she was first born. And then this was like three days after. Newborn photos are their best, gotta do it within the first five days. They don't really start crying until day six. So if you can get photos in day five, all you gotta do is give them a bottle to fall asleep. Great photos. And then here's my wife today. So my daughter's now almost four. And so this is from Halloween. So I'll be honest, I learned so much during this case. Like more than I think I've ever learned during any other one. And I learned how to be a healthcare providers, but also to be a support person. I always say that healthcare providers make the worst patients. It's because if I'm never admitted, you can bet I'm gonna be asking them, what are my labs today? What medications are you giving me? That's dosed incorrectly, please fix it. You know, those sorts of things. That was so tempting. And I asked my wife, we kind of had to sit down. I said, I need to know what role you want me to play in this. Obviously the role of husband is going to be done. Do you want me to be the role of husband and pharmacist or just the role of husband? Because the way I act and react are gonna be very different. And she said, I want you to be husband and pharmacist because I want the best chance for our child. And so that gave me blanket authority to ask very pointed questions, to be at doctor's visits that she probably would not have wanted me at if I wasn't gonna be the one asking so many questions. But she wanted to make sure that we got all the answers so that way we could be more successful. And that was throughout the entirety of the process of which drugs are we using for fertility? What are we gonna do about anticoagulation? I was already asking questions about anticoagulation well before we were even pregnant. So I knew what the plan was once that happened. So that way we could say, okay, we need to go get seen. Because her hematologist oncologist that she had previously was up in Munster, we now live in Indianapolis. So we're going to need to establish care with someone quite quickly. So I want to make sure that we got that on the books. So that was definitely, you know, one of the more sobering things about this. The other thing I realized is it's really easy to say, here go home and do this thing because it's the right answer on an exam or the right answer according to guidelines. And it's a whole nother thing to be the person having to do it. So here, take this injection once a day. Sounds so easy for me to put on the exam as the quote unquote right answer. Doing that with a patient who's deathly scared of needles, who has a child growing in her, a child that is pushing on one side more than the other. So really only one side of her abdomen could be used. They got incredibly bruised and was painful and went through multiple screening episodes as I'm trying to get these injections and try not to get punched in the face. That is really different. And that is really humbling to kind of put yourself into the patient's shoes without asking them. You know, starting a patient who's doing diabetic on insulin, here go home, ***** your finger four times a day, give yourself four different injections and track what you eat. Don't eat this thing, don't eat that thing. Is that really feasible? Some say, yeah, that's what they need to do. They're diabetic, this is the answer. As someone who has a family member going through this issue with diabetes, who's 75, very difficult. And so I just implore you guys as you are going through this course and as you go through whatever the training is after here, to always put yourself in the family member's shoes or the patient's shoes. Because it's very, very different than being the one just to say, oh, this is the right answer. Here, here's five new medications, go start taking these. You're not the one living with the cost of them. You're not the one living with the side effects of them. You're not the one living with the doing it and changing your routine and also knowing that at any moment, you could die of a fatal hemorrhage. So it's very, very, very humbling. So those are a lot of the things that I think we can certainly learn. And I think this one does a really good job of highlighting the fact that chronic illnesses are always chronic. They never leave. So even though this patient was done with treatment, quote unquote, for her thrombophlebitis at 60 days, went nine and a half years without ever thinking twice, that is still chronic disorder and it's so imperative that that remains on their medical chart. If it was not on their chart, none of this would have happened and Lord knows how it would have been different. Additionally, understanding of that pathophysiology is so important because when we start talking about these mutations, we can start making good predictions about maybe what would be better than another drug based off of what the mutation is and the pathophysiology behind it. And then of course, whenever you have a pregnant patient, just like as you pointed out, it's so important to make sure that the medications are safe for both mom, but then also safe for the developing fetus, which is a whole new layer of pharmacology that we have not had to worry about too much yet. You guys will talk about it certainly a lot more next semester when you get to the pregnancy section. The other thing, quick shout out, patient podcast project. There was a graduate, what was Tanner? It was he, 2020? Yeah, it's 2021. 2021, okay. Tanner Maxfield, 2021. I encourage you to listen to this podcast. You're gonna hear a lot of similarities. He interviews his wife and his wife also has factor five Leiden and is also pregnant with at this point their third child, I think. So it's a really interesting perspective as well. I'm not gonna take up the whole time today. That's kind of it for Sandy in her case. I'm happy to answer any questions as it relates to it, but if not, I'll see you guys next week. And we'll start talking about the nitty gritty of anti-coagutantiplatelets. All right, thank you guys.