Cram The Pance - S1E38 Bleeding & Coagulation Disorders

Episode Date: October 13, 2021

Hemophilia A & B, Von Willebrand Disease, Factor V Leiden, Protein C & S Deficiency review for your Pance, Panre and EOR's. DB link (save 10% off by clicking the link!)https://bit.ly/37cP8YP►Paypal Donation Link: https://bit.ly/3dxmTql  (Thank you!)--- Support this podcast: https://anchor.fm/scott--shapiro/supportBecome a supporter of this podcast: https://www.spreaker.com/podcast/cram-the-pance--5520744/support.

All right. So we're going to be only over bleeding and coagulation disorders, specifically hemophilia A and B, Fonwilobrand disease, Factor 5 Lyden, and protein C&S deficiency. Sometimes people have trouble with these. Just, you know, there's not really that much to know, but they can just kind of all get mixed together. And sometimes it's hard remembering which is what. And so I'm going to do my best to focus on the main things that you need to know and help you to just remember them for the exam and what you really need to know for these. So thank you as always for the really great comments.

You guys are absolutely the best and I appreciate it so much. So thank you so much for that. If you haven't checked out, I have an Instagram page and a YouTube channel as well under Cram the Pants. Check those out. There's some other things that may help you for school. So let's go ahead and get started with our bleeding and coagulation disorders. And let's start with the one that you'll probably hear the most about. So that's hemophilia A.

This is your most common type of hemophilia. Not your most common type of bleeding disorder, but your most common type of hemophilia. more common than hemophilia B. So it's the one you'll hear about more between hemophilia A and B, which are very similar between the two. I'll go over the few differences. But essentially clinically, they're the same. Now, this is an X-linked recessive disorder.

So as far as your vignette, this is 100% going to be a male in the vignette. It affects the X chromosome, meaning if a male gets it, males only have one X chromosome. They have the disorder. There's no avoiding it. Females, on the other hand, have two X chromosomes. So they'll still have an unaffected chromosome. So they're usually going to be carriers. The way that I used to remember this was I used to remember hemophilia.

So the name it has phil in it. So hemophilia has fill in it. Phil is a common male name. I always used to just think of Dr. Phil and like his bald head. And as soon as I would see hemophilia, I would say, okay, I know this has to be a male. It would help me narrow it down. So it's little things like this that are going to help you on vignette. So you're going to have a question months from now.

you'll see hemophilia and the answer choices. And you'll remember a damn thing about hemophilia, but you'll remember Dr. Phil's bald head. I'm telling you you will. And then you'll be like, oh, yeah, so this is only seen in males, the patient in the vignette, maybe it's a girl. And you're like, okay, I can eliminate hemophilia. It's not going to be hemophilia because this is a female.

And I remember this is only seen in males. So is it possible with women to have the same presentation as a male? It's possible. It's very rare. It's only if they have like an X chromosome loss or deletion, way beyond the scope of what. what you need to know for the boards again it's rare they're not going to trick you like that so as far as you need to know for the exam this only happens in males look for a male in the vignette

and remember dr phil hemophilia so only males for hemophilia this is a deficiency in factor eight um i used to remember this because when you say the number eight the first thing you say is a so hemophilia a a a to you see what i'm saying so you say a when you say eight so hopefully you makes sense. That used to help me remember it. So, deficiency in factor eight. So as far as the patho, it's really straightforward. You have a deficiency in factor eight. Factor eight is part of the coagulation cascade, specifically the intrinsic pathway. And if you have low factor eight, you have disruption and decreased ability to form clots. Nothing really complicated there. Just remember factor A eight. So, all right, clinical manifestations. These patients are going to bleed. They're going to have

GI tract, bleed, urinary tract, eucosal membranes, intracranial bleeds, a bunch of different ones. But the only one that you need to know, the one that's most unique to hemophilia, that's again what you need to start doing for these exams, focus on the things that are unique, is going to be hemarthrosis. So that's bleeding into a joint space. It's the most common site for bleeding in your ambulatory patients with hemophilia. And it represents close to 80% of the hemorrhages you'll see in hemophilia. So really prominent in this disorder. So as far as clinical manifestations, know this one. How are you going to see it on a vignette, though? they're going to give this to you. So it's going to be a patient. Obviously, it's going to be a male.

It's often going to be a young boy. And they'll say he had a minor accident. He bumped his knee at the playground. Now he has this grossly swollen knee or elbow, wherever they bumped it, basically swelling out of proportion to the injury. They also may mention that he's had this persistently painful joints. He limps on his leg, always complaining of his knees, hurting his ankles, etc. So look for that hemarthrosis. They're going to give it to you in the vignette, because that's the most common presentation. Now, diagnosis, this is important. So your PT, your pro thrombin is going to be normal.

Your PTT, your partial thromboplastin time, is going to be prolonged. So remember PT and PTT are your clotting time to measure how long it takes the form of clot. But why is your PTT prolonged and your Pt is normal? It helps to understand these things to remember them for the exam. So let's go over what PT and PTT measures. So PT measures the extrinsic and the common coagulation pathways. So PT is going to measure 1, 2, 5, and 10 as well as 7. So 7 is going to be the extrinsic pathway.

1, 2, 5, and 10 is going to be the common coagulation pathways. Now, PTT, partial thromoplastin time, the one that's going to be prolonged, again, measures your common pathway. So that's going to be 1, 2, 5, and 10. But it measures the intrinsic pathway as well. And what's included in the intrinsic pathway, that's factors 8, 9, 11, and 12. What did I say there? Eight and nine. So that's specifically what's decreased in hemophilia A is factor eight, and then hemophilia B is factor nine.

So that's why you see a PTT that's going to be prolonged, that's going to be abnormal in hemophilia A and B, because your PTT measures your intrinsic pathway, which includes factors eight, nine, 11, and 12, or PT does not. It only measures the extrinsic, which is going to be factor seven. That's why your PTT is going to be abnormal. normal or prolonged in hemophilia A and B. Just a heads up, it's possible in a patient with mild hemophilia to have a normal PTT. So I always want to do confirmatory testing with a factor 8 assay to see if that's decreased or absent of factor 8.

So remember, your PTT is going to be abnormal. And then you also check for your factor 8 assay to see if that that's decreased or absent. Now, treatment. So there's two things you need to know. Factor 8 in fusion. So they're deficient in factor 8. You give them factor 8. It can be used for prophylaxis.

It can be used during an acute bleed. It's really your best treatment, but it's not your first treatment for hemophilia A. So in hemophilia A, you have another treatment option, and that's with Desmopressin, also known as DDAVP. So Desmopressin, DDAVP is really going to be your first line in mild cases of hemophilia A. So if you have like a little boy who came in to bump his knee, you realize he has hemophilia A, that's what you'll start with.

You're not going to give them these IV Factorade infusions. So you start with Desmoporpefors. So why do you give them desmodepressin? What does DDAVP do? So it stimulates release of something known as Von Willa Brand Factor. And why do we care about releasing Von Willabrand Factor? Well, Von Willabrand Factor Factor is actually partners with Factor 8. It binds to and stabilizes and decreases the degradation of Factor 8. So we have more Von Willowbran Factor with DDAVP. We have an increased stability of Factor 8. So it stays around longer, which is obviously important here. So patients with mild hemophilia A, you have the additional option of DDAVP. Keep in mind,

this is not going to be an option for hemophilia B because hemophilia B involves factor 9 deficiency, which we'll go over next. Vaughan-Willibrand factor has nothing to do with factor 9. These only buddies with factor 8. So you only use this in hemophilia A. What do you need to know for hemophilia A? You need to know it's a factor 8 deficiency. Remember factor A deficiency? You need to know it's going to be a male patient. This is X-linked reset. recessive. So hemophil, Dr. Filia, PTT is going to be increased, but not your PT. Then you need to know, not only can you treat them with factor 8, but you can also treat them with DDAVP, Desmocressin, which is generally going to be your first line treatment for those mild patients.

Hemophilia B. I'm going to run through this one fairly quickly because hemophilia B is almost identical to hemophilia A outside of a couple differences, which I'll go over. The first difference is obviously this is the efficiency in factor 9, not factor 8 like we did in hemophilia A. I used to remember that because I would just remember benign, like the tumor is benign, B9, and that helped me remember hemophilia B. Maybe that does not help you at all, but it always helped me. I never forgot it. So hemophilia B is a factor nine deficiency, benign.

The tumor is benign. X-linked recessive again. Remember, Dr. Phil, this is only going to be seen in males. Females are going to be carriers, but males will be the ones that are going to be symptomatic. Most cases. Clinical manifestations, again, they're going to bleed. G. I track, urinary tract, blah, blah, blah, me, coastal membranes, but you remember hemarthrosis

because that's going to be the most common. So you're going to have that hemorrhage into a joint. Diagnosis, same thing here. PT is going to be normal as well as, I didn't go over this in hemophilia, but as well as your platelets, your fibrinogen, all that's going to be normal. It's just your PTT that's going to be prolonged. Same reason I just went over, because PTT measures your intrinsic, which has factors eight and nine included.

If you ever forget which. measures which measures extrinsic and pttt measures intrinsic this is what i came up with um so you have pt and ptt so in pttt the t and the t are side by side it almost looks like they're holding hands and that's because in pttt t and t are in love aka intrinsic pathway pttt measures the intrinsic pathway because t and t are right next to each other like the top of the ts look like they're holding hands they're in love remember pttt measures the intrinsic pathway, and then PT, you don't see that second T there anymore. What happened? They broke up. They're X's. They're X's. PT measures the extrinsic pathway. T's gone. He's out of the

picture. He or she's out of the picture. They're no longer together. They're X's. So PT measures extrinsic. PTT, they're in love, measures the intrinsic pathway. Hemophilia B is going to measure the factor, or it's going to be a decrease in factor nine. So we also do a factor nine assay. So that's going to be decreased or absent. And treatment, really the key to treatment compared to hemophilia A is only that DDAVP, Desmopressin, plays no role here. Remember what I said before, Desmopresson releases Von Willobrand Factor, Von Willobrand Factor Von Fondon Stabilizes Factor 8. That's not a problem in hemophilia B. We only worry about factor 9. So DDAVP has no role in hemophilia B, only Hymophilia A. So really the main treatment option for

hemophilia B is going to be factor 9 infusion. So again, it could be used for prophylaxis. during an acute leave. It's really your best treatment option for hemophilia B. So what's different compared to hemophilia A as we went through it? Really, there's only two things. First, this is a factor nine deficiency rather than factor eight. And then second, DDAVP is not going to be used. Only factor nine infusions. Otherwise, everything else is pretty much identical. So what you need to know for hemophilia B. Remember, it's a factor nine deficiency, b9, tumor is benign. It's going to be seen in a male patient, Dr. Phil, hemophilia. PTT is going to be increased, but not your PT. And then you use factor nine for treatment, but no DDAVP. DDAVP is not for me in the hemophilia B. All right. So,

von Willa Brand disease is our next one we'll be talking about. So this is a decrease in the quality or the quantity of something known as Von Willa Brand factor. If you remember, I went over this in TTP. In TTP, we had an increase of Von Willowbrant factor, but in this, we have a decrease. So in TTP, we had a clotting problem. In Von Willowbran disease, we're going to have a bleeding problem. That's because von Willowbran factor, or sticky Willie, as I like to call him, his job is to act like glue for platelets, kind of like sticky paper for flies, but in this case for a platelet. So if you have an injury to a blood vessel, you have an opening in the vessel. The body sends Willie to come in, snatch up a bunch of platelets to form this platelet plug.

But in Von Willowbran disease, there's not enough of Willie or Willie's just not doing his job. So the quality of Willie is decreasing. or the quantity. And that's the problem in Von Willa brand disease. You have this ineffective platelet adhesion due to a problem with Willie, which leads to bleeding. Another thing that you need to know for Von Willa brand disease is that it is the most common bleeding disorder. It affects up to 1% of the U.S. population. So it's really common, actually.

There's a few different types of Von Willa Brand factor. There's inherited. There's acquired. Inherited, there's like three different subtypes. Don't worry about that at all. It's insane to make. memorize all of them. And it's a waste of time. The only one that I want you to remember is type one inherited. That's your most common type. About 75% of the cases are type one inherited. Therefore,

that's the one you need to know because that's the one to likely quiz you on. So if on Willowbran disease, remember type one's your most common, about 75% of patients. It's an autosomal dominant disorder. Now clinical manifestations, there's a couple things. You're going to have mucocutaneous bleeding and you're going to have excessive bruising. That's the ones you should know. So there's really just those couple things. So mucocutaneous bleeding like epistasis, bleeding following dental procedures. And then they're also more susceptible to bruising. So there's other clinical manifestations, of course, but those are the ones you should focus on.

They're the more common ones to look out for in the vignette. So remember, look for a nose bleed. They may mention they had a dental cleaning and they held all this excessive bleeding. They may say that they're always bruising or they bruise very easily. That's what you should look out for there. Now, diagnosis, this is going to sound similar. So PT is going to be normal. Your PTT is going to be prolonged.

So that's exactly the same as hemophilia. So why? So why is your PTT prolonged? You told me, I told you before, PTT measures factors in the intrinsic pathway, like factors eight and nine. But this is a Von Willa brand factor problem, not an intrinsic pathway problem. So why is PTT prolonged? Well, it actually is an intrinsic pathway problem.

If you remember what I told you about before with the treatment. So what we talked about before. How is Willie's relationship with factor eight? Remember, Von Willa brand factor essentially protects factor eight. It's like his big brother helps him to stick around longer. While in Von Willa brand disease, there's not enough of Willie around or he's not functioning the way he should. So we're going to have this increased factor eight degradation and less of factor eight overall.

So PTT, which measures the intrinsic pathway, including factor eight, that's why PTT is going to be prolonged in von Willowbran disease because we're having that breakdown of factor eight and that's why we have the same problem that we had in hemophilia. So Von Willowbran disease in general, another thing, it's going to be worse with aspirin use and you may hear that brought up a lot. So your PTT and your bleeding time will also be prolonged with aspirin use. It'll be worse when these patients take aspirin. It's pretty common sense though because as I went over before, Von Willowbran disease is a problem with platelet adhesion. So aspirin's an anti-platelet. So it makes sense this disease is going to be worse. Just remember that because they may bring that up.

that all of a sudden they took aspirin and all of a sudden their symptoms are worse, their bleeding is worse, et cetera. Another thing to look for in the diagnosis, there's Von Willa Brand factor antigen and Von Willa Brand factor activity. Don't go too crazy with this, but just know they're going to be decreased or no platelet aggregation. There's a variety of screening test. You don't need to know all of them.

Just know if they mention a Von Willa Brand factor antigen and it's decreased, most likely going to be Von Willowbran disease. The one thing that I'll mention because it's kind of unique and interesting that maybe will come up, maybe it won't, but the Von Willa Brand Factor activity test, the way that you measure this, and this is, I find it interesting, so maybe it'll help you remember it, is with something called Ristocetan. So Ristocetan, specifically Ristocetan cofactor, it was an antibiotic we used years ago until it was discovered it caused platelet agglutination.

So when you add ristocetan to plasma with normal von willowbrin factor causes all of the platelets to clump together, and you can visualize this coagulation. But when you do the same thing, you add that ristocetan to plasma in a patient that has von willa brand disease, this patient will not have that platelet aggregation. So that's what you're looking for. You actually use this antibiotic that we don't use anymore because of that specific reason to see if this patient has a decreased or non-functioning platelet aggregation, like in patients that have Juan Wollabrand disease. So that's why you use that. And that's how you check the activity of on willowbrant factor.

Now, treatment. Treatment is going to be mainly with DDAVP, Desmopressin, for your mild patients. So desmopressin, as we went over in hemophilia A, I know this is getting repetitive, causes the release of endogenous von WillaBrand factor. And this is going to be the one you'll use most frequently. And the answer likely on the. the vignette is going to be using DDAVP for treatment of Vonwillerbrand disease. You may have also, you have the other options of Von Willowbran Factor Concentrates.

So this is a combination of Von Willowbran Factor in Factor 8 and it's administered intravenously. So you're going to use this in type 3 or severe cases of type 1 and type 2. So this makes sense because DDAVP you can use in mild patients or in type 1. Now type 3, I don't want to go too much into the different types. but just so you kind of understand why we use this instead of DDAVP. So type 3, von Willa Brand disease, you actually have almost no Von Willowbran factor in the body. The body is almost completely depleted. And then if you have type 1 and type 2 severe cases, again, you barely have any DDAVB,

or you barely have any Von Willa brand factor in the body. What does DDAVP do? Well, it encourages the release of endogenous von Willowbran factor. But if you have no von Wynlebran factor in the body, what's DDAVP? what's Desmopressin going to do? Can't do anything if you don't have enough endogenous von Willowbrant factor. And that's why in type 3, which has like no Von Willowbrant factor or in type 1 and type 2, severe enough cases, you don't have enough floating around.

So DDAVP isn't going to do much. So that's why DDAVP, Desmopressin, while it's very useful in mild cases, you can't use it in type 1 and type 2 severe cases or type 3 where there's really like little to no endogenous von Willowbran factor. Hopefully I made that clear enough. Okay. So what do you need to know for Von Willowbran disease? You need to know that this is going to be a decrease in the quantity or the quality of Von Willowbran Factor.

You need to know that these patients are generally going to have mucocutaneous bleeding and easy bruising. And then you need to know as far as treatment, DDAVP is the main thing to focus on, but be aware in certain specific populations like I went over. Von Willoprand Factor Concentrates is going to be another option. All right. Let's move on to Factor 5 Liden. This is a single point mutation in Factor 5. leading to a hypercoagulable state.

Factor 5, it's a part of the clotting cascade, helps form clots by amplifying the production of thrombin. Thrombin is an enzyme that converts fibrinogen to fiber and clots. Anyways, factor 5, he helps us form clots. Thank you for that. Factor 5, that is very helpful. But the problem with Factor 5 is he doesn't really have a stop button. He just keeps going and going and going and helping to make all of these clots.

So someone needs to be around to tell him when to slow down. So then we have a protein that comes from the liver. It's called protein C. Protein C goes up to factor 5, tells him when he's done enough and says protein C to factor 5 says slow down. You've made enough clots. We're good. So that keeps factor 5 under control. So we don't have clots all over the place.

When factor 5 lied in, due to this point mutation that factor 5 now has, he no longer can be cleaved or inactivated by protein C. He does whatever he wants. So think about the point mutation in Factor 5 as earmuffs. He can't hear Protein C telling him to stop anymore. So he just keeps going and going and making more and more clots. So that was a mouthful. But nice and simple, factor 5 makes clots non-stops through the coagulation cascade until Protein C says, okay, that's enough.

Stop factor 5. But in Factor 5, Liden, Factor 5 is no longer listening to Protein C. He's got his earmuffs on. And that leads to this hypercoagulable state and a bunch of clots. So it is the most common cause of inheritable hypercoagulable state, specifically in Caucasian patients. To remember that, this is kind of silly, but it always helped me remember. So factor 5 Lydin, which is FFL, Factor 5 Liden, not the V, like Roman numeral, but factor five Liden, FFL.

To me, stood for frequently forming lumps. That's how I used to remember, like the clots, frequently forming lumps. And then helped me remember it was the most common cause of, of inherited hypercoagulable states. Remember, factor 5 Liden, if you see this patient with clots, that's going to be your most common cause. It'll most likely be the answer. So if they ask you the most common inherited cause of hypercoagulability,

it's factor 5. If they ask you the most common inherited bleeding disorder, remember that's going to be von Willowbran disease. Remember, factor 5 Liden, frequently forming lumps. Hopefully that makes sense or helps you. Clinical manifestations, well, they're going to have venous thromboembolism. So this is going to be the main clinical manifestation. That's what they're going to give you on the vignette.

In real life, only around 5 to 10% of patients with Factor 5 actually go on to develop venous thromboemolism. But anyways, that's what you're going to see on the vignette. So look for your DVTs, your PEs, your clots. Another thing, an interesting thing, is that these patients often have miscarriages. So there's data showing that Factor 5 lighting can lead to unexplained recurrent late pregnancy loss. It's assumed that this is due to the thrombolegged. of the placental vessels.

It's another thing I remember them liking to mention in the vignettes is a history of multiple spontaneous miscarriages. So look for that too with Factor 5 Lighten. Look for your clots. Look for them to mention these miscarriages. Diagnosis, genetic testing is going to be a big one. So if you have a patient that comes in, you suspect Factor 5 Lighten, they have this recurrent venous thromboembolism.

They have a family history of recurrent venous thromboembolism. You're going to look for that point mutinous. we discussed before with genetic testing. Nothing really specific here to know for the exam. Your PT and your PTT are usually going to be normal. You can also do a functional assay to test for protein C resistance. And the protein C resistance, the functional activated protein C resistance, as it's called, you normally do this first.

And if it's positive, then you move on to your genetic testing to confirm just because genetic testing is more expensive. So a lot of times you'll start with your functional activated protein C resistance test. If that's positive, then you move on to your genetic testing. I look for that point mutation. Now, treatment, it's pretty easy. It's really just anticoagulation. So whether it's done prophylactically prior to surgeries or indefinitely depends on the risk

factor of the patient. So what do you need to know? You need to know this is a mutated factor five out of control leading to a hypercoagulable state. Factor five's whiling out. Protein C can't do anything to stop them. Remember, it's the most common inherited cause of hypercugulability. Remember frequently forming lumps.

Look for your venous thromboembolism and your history of miscarriages and then treatment basically with anticoagulants. Pretty simple. All right. Let's move on to our last one. Protein C and S deficiency. There's not a lot to know here. You're going to have a decrease in protein C or protein S, which leads to a hyperquigulable state. So the path, though, don't dive too deep into this because it can become pretty complicated.

But protein C and S, they both come from the liver. They combine with something known. is thrombin and thrombolin. They cleave and inactivate factor five, as we discussed previously. But also protein C also cleaves or inactivates factor eight. And the end result is this prevents excess coagulation or fiber information during secondary hemostasis. So just to make it super simple, what I used to remember, protein S and C stand for stop clots. Protein S and protein C stop clots. That's what they do. They decrease clots by inactive. activating factors five and eight. So deficiencies in either one of these can lead to a hypercoagulable

state because factor five and eight are longer being shut down or cleaved. Clinical manifestations, pretty similar to factor five light and you're going to have your venous thromboembolism. They're more prone to DVTs, PEs. One thing that's a little bit more unique about this, it's not exclusive to protein CNS deficiency, but it's more common. It's something known as warfarin-induced skin necrosis. So patient starts on warfarin in the first few days. They may develop skin necrosis. Why does this happen? Well, it's due to protein C deficiency, but let's actually explain that. If you want to fast forward about 30 seconds, you'll not have to hear this, but I think it's important to kind of understand. So there's a few different mechanisms at

play here. One is just how fast warfarin kicks in. But one of the main causes is actually from a protein seed deficiency. So let's explain why that happens. So patients taking warfarin, when they're first started in the medication, or if there's a, temporary interruption and therapy and they have to restart back on warfarin. They actually should be bridged with heparin or another short acting anticoagulant temporarily for the first few days. Not in all patients, but usually are high risk patients you're going to do this in. And the reason you bridge with heparin or one of those agents is because when you first

start warfarin, you actually get this transient hypercugulable state. So within the first few days, you can potentially start forming all of these clots if you don't bridge with heparin. So you can actually start warfarin to stop clots. And in the first few days, you can cause a bunch of clots. So why does this happen? Well, warfarin works by inactivating your vitamin K-dependent clotting factors. So basically all of the clotting factors coming from the liver, warfarin shuts down. So that's factors 27, 9, 10. But it also, remember what else comes from the liver is protein C and S. So they're also shut down. When all of these factors are shut down at the same time, that's good. We don't have any issues. But the problem is,

they all have different half lives. So protein C has a really short half life, only a few hours. So within a few hours, protein C is actually shut down. It's not coming back due to the warthurn. But your other factors, they have longer half-life. So some of your other coagulation factors actually have half-lifes of two to five days. So it'll be a few days before these are actually shut down. And this is when you have this transient prothoramic state due to your natural anticoagulants,

like protein C disappearing early on and some of your other clotting factors with longer half-life still hanging around for a couple more days. So this leads to clots and ischemia and infarct and that warfarin-induced skin necrosis we talked about due to the protein C deficiency. So it's the absence of protein C altogether that causes this problem. And it's why we bridge warfarin with heparin or another short-acting agent for the first few days in our high-risk patients to prevent this from happening. All right. So diagnosis, you do a protein C and S assay. So there's a variety of assay methods that can measure protein CNS activity or levels. The diagnosis of protein C deficiency is established by just documenting a low protein C or S level.

Genetic testing is not often used. It's not really widely available like we saw in Factor 5 Lydden. So really you're just doing that protein C and S assay. Treatment, again, is going to be anticoagulation like anyone else who develops a clot. You're going to use anticoagulation. It's appropriate for individuals with protein seed deficiency, normally who develop a thrombo-emabolic event. You can also use protein C concentrate.

It's often given prophylactically prior to surgery or in pregnant patients around the time of delivery. What do you need to know for protein C&S deficiency? You need to know this is a protein C&S decreased level, which leads to a hyperquigilible state. Remember, protein S and C have the job of stopping clots. Remember, look for your venous thromboembolism. Also, your warfare and induced skin necrosis,

with that really complicated patho that I explained. And then remember as far as treatment, you're going to use anticoagulation and then protein C concentrate. All right. So let's move on to five questions and we will wrap this up. All right. So question one. A seven-year-old boy presents to the office today with significant swelling over his right knee. Other states they were at the playground and he bumped his knee on the slide as he was coming down.

She states he's always bruised very easily and often complains of joint pain. Regulation studies show a prolonged PTT, and plasma factor eight assays show decreased levels of factor eight. What would be the first line pharmacologic agent to administer in this patient? So that is going to be Desmopressin, also known as DDAVP. So this patient has a clear presentation of hemophilia A, male gender, remember hemophilia, X-linked recessive, remember hemarthrosis, which is the most common manifestation in your ambulatory patients with hemophilia, patient had a prolonged PTT, decrease factor eight,

So we know it's hemophilia A. And how do we treat mild cases of hemophilia A like this boy obviously had? That's going to be with DDAVP, which increases the release of endogenous von Willowbran factor. That stabilizes factor 8 in the body. Question two. What is the most common inherited bleeding disorder? That is going to be von Willa brand disease seen in up to 1% of the population.

Question three, 39-year-old female presents to the ER with lower leg pain and swelling. A Doppler of the lower extremity is performed. which reveals a DVT. She admits this is her third DVT in the last few years. She also has a history of several miscarriages and admits her mother had similar problems with blood clots. Genetic testing in this patient would likely reveal a mutation in which clotting factor.

So that's going to be factor five. So first, factor five Lydin is your most common cause of inherited hypercoagulable states. So always be thinking factor five before anything else, protein C rest deficiency. see, remember frequently forming lumps. So, especially in your Caucasian patients, which Factor 5 Lydin is seen much more commonly in. So patient has multiple DVTs.

We have a family history of DVTs plus miscarriages, which we know is another potential problem in Factor 5 Liden. So the most likely cause of this problem is by this patient having a mutation in Factor 5, leading to the resistance to it being broken down by protein C. Question four, hemophilia B is a deficiency in which clotting factor. So that is going to be factor nine. Remember, the tumor is benign, benign. All right.

Question 5, a 52-year-old female who was recently started on warfarin for DVT prophylaxis begins to develop necrotic lesions on her legs and feet. Deficiency in which vitamin K-dependent plasma protein likely led to this presentation. That's going to be protein C. So this patient has warfarin-induced skin necrosis. So remember with warfarin, the reason we bridge with heparin or low-molecular weight heparin in our high-risk patients is that tranrain. transient prothrombic state, where warfarin initially, where the protein C and S get shut down,

and our natural anticoagulants, and then the other factors takes a few days to get shut down. So we have that deficiency in factor or in protein C, which leads to this prothrombic state. So that is it. I hope that was helpful. Thank you so much for listening. Please let me know if it's helping you or if there's any suggestions you guys have for topics coming up or anything else, really. So thank you so much as always and good luck on your pants, your panor, your EORs, and good luck in PA school.