WEBVTT - Ep 79 Hemophilia: A Hemorrhagic Disposition 0:00:01.880 --> 0:00:04.800 As long as I could remember, in my early childhood, 0:00:05.120 --> 0:00:08.800 I always knew that my dad had hemophilia. I can 0:00:08.840 --> 0:00:12.440 specifically remember we had a whole shelf in our refrigerator 0:00:13.000 --> 0:00:17.680 full of these little white boxes of factor nine, which 0:00:17.800 --> 0:00:19.800 as a kid, I didn't really know what they were, 0:00:19.840 --> 0:00:22.720 but I knew, like, pretty frequently my dad would have 0:00:22.760 --> 0:00:25.400 to take one of those boxes into his room and 0:00:25.440 --> 0:00:27.040 he'd close the door and we'd have to leave him 0:00:27.040 --> 0:00:30.160 alone for an hour, and as I learned as I 0:00:30.200 --> 0:00:34.159 got a little older, he would be transfusing himself with 0:00:34.560 --> 0:00:39.760 factor nine. He was a wonderful dad, but you know, 0:00:39.880 --> 0:00:44.479 because of a long history of bleeding into his joints, 0:00:44.960 --> 0:00:47.479 he couldn't interact with us the same way maybe other 0:00:47.560 --> 0:00:51.440 dads would. He had a lot of joint pain and 0:00:51.479 --> 0:00:54.760 it was visible in his hands and his feet, and 0:00:54.800 --> 0:00:57.360 he would try his best, but I think I drove 0:00:57.440 --> 0:01:00.880 him crazy wanting to be carried constantly, which he could 0:01:00.880 --> 0:01:03.800 not do, and we just always wanted to, you know, 0:01:03.920 --> 0:01:07.240 play like little kids do, and he'd have to try 0:01:07.240 --> 0:01:09.839 his best and then step back from that. I'm sure 0:01:09.880 --> 0:01:13.280 we probably contributed to him needing to transfuse more than 0:01:13.959 --> 0:01:18.000 otherwise he would have but that's okay. He never minded, 0:01:18.440 --> 0:01:24.440 He never complained at all. So when I reached around puberty, 0:01:25.640 --> 0:01:29.080 maybe I was told earlier, but I definitely distinctly remember 0:01:29.120 --> 0:01:35.080 being told, you know, hemophilia is genetic, and that they 0:01:35.280 --> 0:01:38.320 found out when I was born that I was a carrier, 0:01:38.680 --> 0:01:40.280 but they would need to find out if I was 0:01:40.319 --> 0:01:46.040 a symptomatic carrier. So in my probaly between ten and twelve, 0:01:46.880 --> 0:01:50.000 went to the hospital, got some tests done and found out, 0:01:50.040 --> 0:01:52.760 sure enough, I am a carrier, and not only that, 0:01:52.880 --> 0:01:58.400 but a symptomatic carrier. Nowadays, they actually just consider women 0:01:58.480 --> 0:02:02.480 who carry that gena dar symptomatic to just have chemophilia. 0:02:02.560 --> 0:02:07.240 They don't call symptomatic carriers anymore. So, like my dad 0:02:07.400 --> 0:02:11.080 and actually both of his brothers, I have hemophilia B, 0:02:11.760 --> 0:02:16.360 a factor nine deficiency. Unlike them, mine is mild and 0:02:16.639 --> 0:02:19.799 doesn't affect my life day to day, since two out 0:02:19.840 --> 0:02:21.800 of the three of them are no longer alive to 0:02:21.840 --> 0:02:24.840 speak to their own stories and tell you a little 0:02:24.880 --> 0:02:29.480 about them. So, my dad and his older brother both 0:02:29.520 --> 0:02:34.600 had very severe chemophilia B. They produced zero factor nine 0:02:34.639 --> 0:02:37.880 on their own, and they were born in the nineteen fifties, 0:02:38.360 --> 0:02:43.800 which was before pretty much any good treatment existed. All 0:02:43.840 --> 0:02:47.519 three brothers, actually, my grandmother used to tell me, they 0:02:47.600 --> 0:02:51.600 refused to cooperate with all the restrictions on their behavior, 0:02:52.240 --> 0:02:55.880 and at the time, the lifespan for them was expected 0:02:55.880 --> 0:02:58.480 to only be into their twenties, so my grandmother tried 0:02:58.480 --> 0:03:01.040 as hard as she could to keep three young boys 0:03:01.280 --> 0:03:05.440 well contained, and they didn't cooperate at all. My dad 0:03:05.440 --> 0:03:08.240 even at one point took me down the road from 0:03:08.240 --> 0:03:10.440 his old house to show me the field where they 0:03:10.440 --> 0:03:14.120 would all go play football and subsequently all need to 0:03:14.160 --> 0:03:17.360 be driven to the hospital to get blood transfusions. So 0:03:17.520 --> 0:03:21.640 my grandmother said their childhood was full of at least 0:03:21.639 --> 0:03:24.560 one trip to the hospital every week, and it was 0:03:24.600 --> 0:03:28.079 so frequent that their pediatrician would actually pick them up 0:03:28.160 --> 0:03:32.000 at her house and bring them there himself. I can't 0:03:32.000 --> 0:03:37.400 imagine having a childhood like that, and I also suspect 0:03:37.400 --> 0:03:41.160 it probably contributed to a lot of the symptoms my 0:03:41.280 --> 0:03:45.040 dad had just from just constant bleeding. But I also 0:03:45.120 --> 0:03:49.320 can't imagine living a life as restricted as kids with 0:03:49.440 --> 0:03:54.080 humohilia really needed to Back then, when I was actually 0:03:54.120 --> 0:03:57.400 soon after I found out that I was also a 0:03:57.440 --> 0:04:04.240 carrier and symptomatic with humophilia. My uncle became symptomatic with 0:04:04.640 --> 0:04:08.800 his HIV, had SYRUH converted to AIDS, and I never 0:04:08.880 --> 0:04:12.200 knew growing up that he had HIV, and I never 0:04:12.280 --> 0:04:15.440 knew that my dad had hepatitis C. But when he 0:04:15.520 --> 0:04:19.680 got really sick, my dad found it important to sit 0:04:19.760 --> 0:04:23.320 us down and tell both me and my sister that 0:04:23.320 --> 0:04:27.440 that they both developed HIV, and then my dad HEPSI 0:04:28.040 --> 0:04:31.400 and my uncle as well HEPSI as a result of 0:04:31.560 --> 0:04:35.880 blood transfusions and blood products because back when they were 0:04:35.920 --> 0:04:39.520 young and getting them, they didn't know that they contained 0:04:39.560 --> 0:04:44.800 all these viruses. And they told me then that about 0:04:45.200 --> 0:04:48.880 half of all people with hemophilia back then would go 0:04:48.920 --> 0:04:51.240 on to get these diseases, and never really gave me 0:04:51.279 --> 0:04:53.760 a number on how many of them died, but I 0:04:53.880 --> 0:04:57.560 understood them that it was pretty grave. So when I 0:04:57.600 --> 0:05:01.559 was fourteen, my uncle passed away from implications from HIV 0:05:01.640 --> 0:05:05.160 and AIDS that again he contracted as a result of 0:05:05.360 --> 0:05:09.560 treatment for his hemophilia. When I was in my early twenties, 0:05:09.720 --> 0:05:13.160 my dad also passed away from complications of hepatitis C, 0:05:14.560 --> 0:05:20.920 again from requiring blood products for hemophilia. I remember for 0:05:21.080 --> 0:05:25.400 my dad it was really profound he actually, up until 0:05:25.440 --> 0:05:27.839 the point that he got really critical with his hepsia, 0:05:28.000 --> 0:05:31.840 had said that it was almost like a silver lining 0:05:32.560 --> 0:05:36.040 of hemophilia to get hepatitis c because a liver transplant 0:05:36.040 --> 0:05:40.719 actually would have functionally cured his hemophilia, and he felt 0:05:40.720 --> 0:05:43.560 that life post transplant would have been a better quality 0:05:43.600 --> 0:05:48.520 than that of living with hemophilia, even with home transfusions 0:05:48.560 --> 0:05:55.200 and all the other treatment options, which is really devastating 0:05:55.240 --> 0:06:00.200 to think about, especially knowing how positively he viewed life 0:06:00.240 --> 0:06:06.000 and how little he complained. So for me personally, like 0:06:06.080 --> 0:06:09.560 I said, day to day, my quality of life isn't impacted, 0:06:09.680 --> 0:06:13.880 although I do have other medical issues and hemophilia always 0:06:13.920 --> 0:06:16.920 complicates those. So when I go to a doctor and 0:06:16.960 --> 0:06:21.800 we're talking about treatment options for other things, my bleeding 0:06:22.080 --> 0:06:25.159 and clouding status is always at the forefront of my 0:06:25.240 --> 0:06:30.359 doctor's minds. Whether I need to be hospitalized inpatient for 0:06:30.520 --> 0:06:33.480 something that other people would go home from the same day, 0:06:34.120 --> 0:06:38.440 whether I need to be infused with factor before during 0:06:38.640 --> 0:06:42.520 after the next day, whether I need to take something 0:06:42.560 --> 0:06:47.359 like amacar for a mild procedure, and even down to 0:06:47.920 --> 0:06:49.960 the reason I had had to go back when I 0:06:50.080 --> 0:06:55.320 hit puberty for periods which are heavy and really unpleasant, 0:06:55.760 --> 0:06:58.400 which everybody deals with, I'm sure, but for someone with 0:06:58.520 --> 0:07:04.479 heem affiliates particular gularly burdensome. And I always worry if 0:07:04.480 --> 0:07:06.520 I get into a car accident or some sort of 0:07:06.560 --> 0:07:10.160 other trauma, if I don't go to a hospital that 0:07:10.200 --> 0:07:12.400 has my records or my husband's not with me to 0:07:12.600 --> 0:07:15.800 tell somebody when I'm bleeding. Will they give me normal 0:07:15.840 --> 0:07:19.280 blood or red blood cells, which will only thin out 0:07:19.360 --> 0:07:23.840 my factor levels even more, dilute them even more, or 0:07:24.600 --> 0:07:29.680 will I be okay? But mostly I'm grateful that I 0:07:29.760 --> 0:07:33.400 was born when I was in the eighties. I'm grateful 0:07:33.480 --> 0:07:36.600 that one of my uncles is still alive, that he 0:07:36.680 --> 0:07:39.560 was born later than the other two and has suffered 0:07:39.640 --> 0:07:42.880 less because things like cryo precipitate were already known about 0:07:43.240 --> 0:07:48.720 in his early childhood. And other than that, I think 0:07:48.760 --> 0:07:53.920 that hemophilia is It's not something we hear about regularly, 0:07:54.080 --> 0:07:57.960 but it's it's a fascinating look at a disease that 0:07:58.040 --> 0:08:02.960 can just ravage an entire family line, one that can 0:08:03.280 --> 0:08:08.320 have devastating impacts if it's not diagnosed early. Living with 0:08:08.520 --> 0:08:13.000 humophilia now is so much easier than it used to be. 0:08:13.520 --> 0:08:16.320 But I think that even though the treatment options have 0:08:16.440 --> 0:08:20.120 improved dramatically, we can look back at the very recent 0:08:20.280 --> 0:08:24.600 history of this disease and see that it's really important 0:08:24.680 --> 0:08:28.760 to evaluate, you know, looking for treatment options, but also 0:08:28.800 --> 0:08:32.520 evaluating the safety of them, because the impacts that they 0:08:32.520 --> 0:08:35.680 can have on the people that we're treating can be 0:08:35.760 --> 0:09:19.760 really devastating. 0:09:22.720 --> 0:09:25.600 Thank you so much for taking the time to chat 0:09:25.600 --> 0:09:27.520 with us and for sharing your story. 0:09:28.080 --> 0:09:28.920 We appreciate it. 0:09:29.760 --> 0:09:31.960 Hi, I'm erin Welsh. 0:09:31.440 --> 0:09:33.319 And I'm erin Oman Updyke. 0:09:33.280 --> 0:09:35.520 And this is this podcast will Kill You. 0:09:36.000 --> 0:09:39.839 And welcome. I lost track of our episode numbers again. 0:09:40.040 --> 0:09:41.480 It's over seventy something. 0:09:41.960 --> 0:09:47.040 Yeah, I think this is seventy nine. How I know, 0:09:47.280 --> 0:09:50.600 let us go, I know, I know we're getting up there. 0:09:50.720 --> 0:09:51.400 We really are. 0:09:52.120 --> 0:09:52.320 Well. 0:09:52.360 --> 0:09:56.000 Welcome everyone. I'm pretty excited about this episode me too. 0:09:56.360 --> 0:10:01.600 It's kind of an unusual one, different in that for 0:10:01.640 --> 0:10:04.600 a number of reasons. Number one, it's not an infectious 0:10:04.640 --> 0:10:08.520 disease m H. And number two maybe this doesn't make 0:10:08.559 --> 0:10:12.640 it different, but like the research turned out to be 0:10:12.679 --> 0:10:14.079 a lot different than I expected. 0:10:14.880 --> 0:10:17.600 Yeah for me as well. And I'm really excited about 0:10:17.640 --> 0:10:20.840 the biology section because it's totally different than what I 0:10:20.920 --> 0:10:22.360 normally do in this series. 0:10:22.679 --> 0:10:24.040 Yeah, I feel like it's going to be a really 0:10:24.040 --> 0:10:26.440 interesting one to kind of dive into parts that we 0:10:26.520 --> 0:10:30.400 don't usually talk about or have only touched on briefly. Yeah, 0:10:30.440 --> 0:10:33.680 and also because the history for this is so massive, 0:10:34.320 --> 0:10:38.000 I like barely stumbled onto any biology, and so I'm 0:10:38.400 --> 0:10:42.400 really excited to learn exactly how these different things happen. 0:10:42.520 --> 0:10:45.640 But arin, what are we talking about today? Today? 0:10:45.679 --> 0:10:47.720 We're talking about hemophilia. 0:10:48.240 --> 0:10:52.320 Yes we are, which is also kind of like with 0:10:52.400 --> 0:10:56.840 our last episode, Bartonella, an umbrella term for a lot 0:10:56.880 --> 0:10:58.600 of different types of things. 0:10:58.920 --> 0:11:01.320 It is, it is. But luckily the biology is not 0:11:01.480 --> 0:11:05.160 nearly as confusing as Bartonella. It's like all very straightforward. 0:11:05.240 --> 0:11:09.280 It would be surprising if it were as confusing as Martinella. 0:11:09.320 --> 0:11:12.040 I don't know if there's anything quite as confusing as that. 0:11:12.480 --> 0:11:13.760 Let's hope. Let's hope not. 0:11:14.080 --> 0:11:15.480 Yeah. 0:11:15.600 --> 0:11:18.200 Well, in the interest of how long this episode's going 0:11:18.280 --> 0:11:21.160 to be, I think it's about time for a quarantini 0:11:21.640 --> 0:11:22.240 it is. 0:11:23.160 --> 0:11:24.640 What are we drinking this week? 0:11:25.040 --> 0:11:29.240 We're drinking the transfusion. Get it, like a blood blood 0:11:29.240 --> 0:11:30.959 transit you get it? You can up with it. 0:11:31.040 --> 0:11:32.000 I get it. I get it. 0:11:33.440 --> 0:11:35.080 Aaron, what's in the transfusion? 0:11:35.640 --> 0:11:41.840 It is whiskey, simple syrup, blood, orange juice, lemon juice, 0:11:41.880 --> 0:11:43.720 lime juice, and grenadine. 0:11:44.280 --> 0:11:47.600 Niceon red, very red, very red. 0:11:48.160 --> 0:11:51.199 And we will post the full recipe for this quarantini 0:11:51.320 --> 0:11:54.160 as well as the non alcoholic place sy burrita on 0:11:54.200 --> 0:11:56.839 our website This podcast will kill You dot Com, as 0:11:56.880 --> 0:11:59.960 well as on all of our social media channels. 0:12:00.000 --> 0:12:02.480 Speaking of our website, this podcast would kill you dot Com. 0:12:02.520 --> 0:12:05.320 If you haven't checked it out, you should definitely do so. 0:12:05.440 --> 0:12:09.800 We have so many things there, from merch to transcripts, 0:12:10.000 --> 0:12:14.079 to links to our music, to our Patreon to every 0:12:14.200 --> 0:12:17.160 source we've ever used in an episode. We've got bookshop, 0:12:17.240 --> 0:12:19.560 We've got a good Reads list. Oh my gosh, there's 0:12:19.600 --> 0:12:21.240 so much there. Check it out. 0:12:21.440 --> 0:12:24.679 Yeah, there's a lot, there's a long list. 0:12:24.720 --> 0:12:25.680 I ran out of breath. 0:12:25.840 --> 0:12:29.439 Well, I think that's good timing because I think we're 0:12:29.480 --> 0:12:31.760 ready to just dive into the episode. 0:12:32.080 --> 0:12:33.760 I think, so this is going to be a good one. 0:12:33.840 --> 0:12:38.360 Let's take a quick break and then get straight to it. 0:13:08.240 --> 0:13:11.400 So Hemophilia, I'm not gonna step on your toes erin, 0:13:11.520 --> 0:13:17.560 but obviously Heme is blood and phil is love, so 0:13:17.679 --> 0:13:19.760 hemophilia is love to bleed. 0:13:20.360 --> 0:13:23.400 I okay, I don't really love that name for it. 0:13:23.440 --> 0:13:24.200 I don't know why. 0:13:24.520 --> 0:13:27.920 It's not great, but it's very what is it Greek, 0:13:28.160 --> 0:13:34.880 Latin Latin? Sure? Yeah. Anyways, So hemophilia is a disorder 0:13:35.000 --> 0:13:40.040 of blood clotting, and once you understand what is missing, 0:13:40.200 --> 0:13:44.640 what the essential underlying problem is, all of the symptoms 0:13:44.679 --> 0:13:47.920 that make up the disorder become incredibly clear because they're 0:13:48.040 --> 0:13:52.840 essentially just problems that will then lead to bleeding, which spoiler, 0:13:53.200 --> 0:13:57.160 those are the main symptoms. So this episode's fun because 0:13:57.280 --> 0:14:01.800 we're gonna go over in very general terms some really 0:14:01.920 --> 0:14:05.640 basic human biology, and that is the clotting cascade. 0:14:06.040 --> 0:14:09.240 Oh okay, I was hoping I was gonna learn about this. 0:14:09.640 --> 0:14:12.160 That's pretty much gonna be the main that's the whole 0:14:12.200 --> 0:14:16.080 biology section. Great, okay, because once you understand how our 0:14:16.120 --> 0:14:19.200 blood normally clots, then all of the problems that arise 0:14:19.200 --> 0:14:22.720 from hemophilia, they're just like an extension of that. It's 0:14:22.760 --> 0:14:26.080 a direct consequence of interrupting this clotting process. 0:14:26.200 --> 0:14:26.920 Right, Okay. 0:14:27.560 --> 0:14:30.480 I will say upfront, if you are someone who needs 0:14:30.760 --> 0:14:34.200 or wants to memorize all of the details of this process, 0:14:34.320 --> 0:14:37.080 like every number of every factor. I'm not going to 0:14:37.160 --> 0:14:39.120 go into that, but I'll link to a con Academy 0:14:39.200 --> 0:14:42.840 video that's excellent. We're just gonna go over it in 0:14:42.880 --> 0:14:47.240 pretty broad strokes, all right, So everyone knows that our 0:14:47.280 --> 0:14:50.640 blood is very important in our bodies. It's how we 0:14:50.680 --> 0:14:54.080 carry nutrients and oxygen to all of our tissues, and 0:14:54.200 --> 0:14:57.840 it's how our cells offload carbon dioxide and waste products 0:14:57.880 --> 0:14:59.680 to be carried to our lungs, our liver, et cetera. 0:15:00.480 --> 0:15:04.720 And in our human bodies, blood is inside of blood vessels, 0:15:05.000 --> 0:15:08.200 and that's where it's supposed to remain. If the walls 0:15:08.200 --> 0:15:12.120 of our blood vessels get broken, we bleed. We all 0:15:12.160 --> 0:15:14.840 know this, right. If you get a cut on your skin, 0:15:15.120 --> 0:15:17.560 you break the walls of tiny little blood vessels and 0:15:17.600 --> 0:15:22.760 you bleed. And because bleeding outside of our vessels is bad, 0:15:23.440 --> 0:15:26.960 our body has mechanisms to stop this from bleeding. Everything 0:15:27.000 --> 0:15:30.640 from tiny scratches up to larger breaks in the vessels. 0:15:31.920 --> 0:15:35.000 So very broadly, when a blood vessel wall gets disrupted, 0:15:35.200 --> 0:15:39.120 there's kind of a series of three steps that happen 0:15:39.360 --> 0:15:43.880 to fix it. First, you plug the hole like stick 0:15:43.920 --> 0:15:46.160 your finger in it kind of plug, just so that 0:15:46.200 --> 0:15:49.720 you don't lose any more blood. Second, you a fix 0:15:49.800 --> 0:15:52.240 that plug into place with something a little bit more 0:15:52.280 --> 0:15:55.880 sturdy so it doesn't come unplugged in like the near term. 0:15:56.120 --> 0:15:58.400 And then finally you have to prepare that whole area, 0:15:58.480 --> 0:16:00.920 if possible, so you don't break it in the same spot. 0:16:01.320 --> 0:16:01.640 Right. 0:16:02.440 --> 0:16:03.840 So, the way I like to think of it is 0:16:03.880 --> 0:16:06.560 if our bodies were like the plumbing under your sink. 0:16:07.680 --> 0:16:10.200 You're like, oh my god, I just sprung a leak. 0:16:10.400 --> 0:16:11.960 I don't want to flood my whole house. So you 0:16:12.000 --> 0:16:13.680 pull your gum out of your mouth and shove it 0:16:13.680 --> 0:16:17.040 over the leak step one. And then you go search 0:16:17.120 --> 0:16:19.080 your whole house to find the duct tape that you 0:16:19.160 --> 0:16:22.120 know you had somewhere, and you secure that gum in 0:16:22.160 --> 0:16:24.240 place with a whole bunch of duct tape just to 0:16:24.400 --> 0:16:27.000 keep it until you can call the plumber, who might 0:16:27.080 --> 0:16:30.040 take their sweet time getting over there. But that duct 0:16:30.040 --> 0:16:32.080 tape is strong, so it'll hold it until it can 0:16:32.080 --> 0:16:35.680 be fixed properly. Easy, easy, Right, That's what we do 0:16:35.760 --> 0:16:39.600 in our human pipes. When a blood vessel wall is disrupted, 0:16:39.640 --> 0:16:42.840 the first thing that happens is our platelets, which I 0:16:42.920 --> 0:16:45.160 feel like we've talked about a bit on this podcast. 0:16:45.840 --> 0:16:48.960 Platelets are just these little cells, kind of little chunks 0:16:48.960 --> 0:16:52.640 of cells that are in our bloodstream and they're super sticky, 0:16:53.160 --> 0:16:56.040 so they float past that hole in the blood vessel 0:16:56.040 --> 0:16:59.119 wall and they stick themselves. They turn on their stickiness 0:16:59.200 --> 0:17:02.800 and they stick themselves to just plug that hole. First thing, 0:17:03.560 --> 0:17:07.960 gum in the hole. That's your platelets. But gum that 0:17:08.040 --> 0:17:10.320 you just threw down in a panic doesn't hold that 0:17:10.359 --> 0:17:14.479 flow forever. And obviously in our bodies, we can't just 0:17:14.520 --> 0:17:17.919 like find duct tape, right because if you had a 0:17:17.960 --> 0:17:20.360 bunch of duct tape just floating around your bodies, you'd 0:17:20.359 --> 0:17:24.360 be clogging up your pipes because duct tape is really sticky. 0:17:25.040 --> 0:17:27.800 So we in our bodies have to actually make the 0:17:27.880 --> 0:17:32.240 duct tape from scratch, and that is where the coagulation 0:17:32.320 --> 0:17:33.040 cascade comes in. 0:17:33.240 --> 0:17:36.280 Ahhh okay, okay, So. 0:17:36.320 --> 0:17:39.760 The duct tape in our bodies is a substance called fibrin. 0:17:40.800 --> 0:17:45.560 Fibrin is a really strong sticky protein that cross links 0:17:46.119 --> 0:17:49.240 kind of just like duct tape honestly, and forms these 0:17:49.359 --> 0:17:53.080 chains to make a really nice solid patch to hold 0:17:53.080 --> 0:17:56.120 that blood vessel wall until we can call the plumber 0:17:56.440 --> 0:18:03.119 and actually repair those endothelial cells themselves. But like I said, 0:18:03.119 --> 0:18:06.360 fibrin doesn't just float around our bloodstream freely. It has 0:18:06.440 --> 0:18:10.040 to be activated before it can do its job. And 0:18:10.080 --> 0:18:13.160 the series of events that have to take place, it's 0:18:13.240 --> 0:18:16.639 kind of maybe I'm getting too excited about it, but 0:18:17.040 --> 0:18:20.280 it is the coagulation cascade. And if any listeners have 0:18:20.320 --> 0:18:22.800 seen this drawn out on paper aerin, you probably have 0:18:23.160 --> 0:18:24.400 way long time ago. 0:18:24.640 --> 0:18:26.080 Right, probably probably. 0:18:26.560 --> 0:18:30.480 It's like a Y shaped little graphic. It has two 0:18:30.960 --> 0:18:33.480 arms and then they come together at the bottom because 0:18:33.520 --> 0:18:37.720 the bottom is fibrin. So it's a process that begins 0:18:37.840 --> 0:18:41.560 as soon as a vessel wall is disrupted. It involves 0:18:41.960 --> 0:18:47.160 twelve different proteins, although they're numbered like one through thirteen, 0:18:47.520 --> 0:18:48.800 and there's no number six. 0:18:50.280 --> 0:18:52.520 Okay, okay, listen. 0:18:52.880 --> 0:18:55.080 They thought that six was turned out to be a 0:18:55.119 --> 0:18:57.560 part of another one they had named one six and 0:18:57.560 --> 0:18:59.680 then it was like, oh, just kidding, that's something else 0:19:00.320 --> 0:19:06.160 like Pluto of exactly poor Pluto. So all these different 0:19:06.160 --> 0:19:09.960 proteins are called factors factor one through thirteen minus six, 0:19:10.680 --> 0:19:14.800 and they all essentially help catalyze the activation of each 0:19:14.840 --> 0:19:18.440 other down a chain. Really, it's down two different arms 0:19:18.440 --> 0:19:21.919 of a chain that lead to the same place, and 0:19:21.960 --> 0:19:26.880 that same place is an exponential increase in activated fibrin 0:19:27.160 --> 0:19:30.919 aka duct tape. I'm not going to go over the 0:19:31.000 --> 0:19:35.399 specific series of events because it's not really that important 0:19:35.640 --> 0:19:40.400 for this, but you can imagine that if number one 0:19:40.640 --> 0:19:44.760 is fibrin, which it is, and number twelve is like 0:19:44.960 --> 0:19:47.280 the top of the chain, you kind of are moving 0:19:47.440 --> 0:19:51.440 down to try and make fibrin. So anything that's missing 0:19:52.040 --> 0:19:57.719 or doesn't work correctly between numbers two and eleven means 0:19:57.800 --> 0:20:00.600 that you're going to interrupt that whole process and not 0:20:00.680 --> 0:20:02.119 be able to make fibrine. 0:20:02.400 --> 0:20:05.639 But the interruptions are not equal, right in that, like, 0:20:05.840 --> 0:20:08.480 if you stop earlier on, you're gonna have an even 0:20:08.880 --> 0:20:12.520 less finished product than if you stop at like factor ten. 0:20:13.119 --> 0:20:17.080 Absolutely, yes, okay, And on top of that, there's two 0:20:17.320 --> 0:20:20.479 arms of this chain, so even if you're missing, you know, 0:20:20.640 --> 0:20:23.359 a bunch of one of those arms, you'll still have 0:20:23.440 --> 0:20:27.680 a little bit with that other arm, gotcha. So yes, However, 0:20:28.640 --> 0:20:32.000 a disruption anywhere in that chain is going to affect clotting, 0:20:32.200 --> 0:20:33.719 but all to a different degree. 0:20:34.119 --> 0:20:34.560 Mm hmm. 0:20:35.040 --> 0:20:37.439 So it's a fairly complex series of events, but It 0:20:37.480 --> 0:20:40.600 makes sense that it's complex because this is a process 0:20:40.640 --> 0:20:44.880 that you do not want happening uncontrolled. Right, It's very 0:20:44.920 --> 0:20:48.240 important to be able to form these super stable clots, 0:20:48.480 --> 0:20:51.000 but you don't want this process running a muck and 0:20:51.080 --> 0:20:54.959 making clots when it shouldn't because when that happens, and 0:20:55.080 --> 0:21:00.879 it does, that's called a thrombophilia, meaning you love making clots. 0:21:01.200 --> 0:21:04.639 Right, and so it's deadlier to have more of the 0:21:04.680 --> 0:21:07.760 stuff running around, probably, which is why there are so 0:21:07.800 --> 0:21:09.600 many switches that need to be activated. 0:21:10.000 --> 0:21:14.080 Right. I don't have numbers on whether they're equally deadly 0:21:14.200 --> 0:21:15.520 or not, but they're both bad. 0:21:15.680 --> 0:21:16.480 They're both bad. 0:21:16.560 --> 0:21:21.120 Yeah, yeah, So yeah, it's this series of events. That's 0:21:21.160 --> 0:21:25.080 why we call it a cascade. Each step from twelve 0:21:25.280 --> 0:21:29.240 to ten to nine and eight to five. It actually 0:21:29.320 --> 0:21:35.920 goes from twelve to eleven to nine. Long story. Each 0:21:35.960 --> 0:21:38.040 step has to take place in order to build that 0:21:38.119 --> 0:21:43.600 final product, like an assembly line. So hemophilia is a disorder. 0:21:43.680 --> 0:21:48.720 It's several disorders that interrupt this process because of either 0:21:48.880 --> 0:21:55.320 inadequate production or production but incorrect or inadequate activity of 0:21:55.359 --> 0:22:00.919 certain factors in this clotting cascade. Okay, so, like you mentioned, 0:22:00.960 --> 0:22:04.520 Aaron early on. There's a number of different types of hemophilia. 0:22:05.359 --> 0:22:09.080 They all have slightly different clinical pictures, but overall, if 0:22:09.160 --> 0:22:11.679 you think of them as not being able to clot 0:22:11.760 --> 0:22:16.760 blood efficiently, then they're all pretty similar. So hemophilia A, 0:22:17.200 --> 0:22:19.760 which is the most common, is when you have a 0:22:19.800 --> 0:22:24.600 problem in the production of factor eight. That's one very 0:22:24.680 --> 0:22:28.920 important factor in the clotting cascade. Hemophilia B is when 0:22:28.960 --> 0:22:32.280 there's a problem with the production of factor nine. And 0:22:32.400 --> 0:22:35.520 those two are the kind of main diseases that we 0:22:35.600 --> 0:22:39.840 call hemophilia, And they actually look very similar because factor 0:22:39.960 --> 0:22:42.960 nine in factor eight work together in the clotting cascade. 0:22:43.720 --> 0:22:47.160 So those two diseases are like very very similar. Clinically 0:22:47.560 --> 0:22:50.159 they look about the same. You have to do like 0:22:50.440 --> 0:22:53.280 factor analysis how much factor eight versus how much factor 0:22:53.400 --> 0:22:54.840 nine do you have in your blood to know which 0:22:54.840 --> 0:22:55.280 one you have? 0:22:55.600 --> 0:22:56.480 Okay, gotcha. 0:22:56.960 --> 0:23:00.960 But then there are other hemophilias. Hemophilias is really the 0:23:01.000 --> 0:23:05.359 only other one that's often called like hemophilia proper, and 0:23:05.400 --> 0:23:08.600 that's a problem in the production of factor eleven. But 0:23:08.840 --> 0:23:12.440 problems at any point along this cascade lead to varying 0:23:12.600 --> 0:23:17.480 degrees of what we call coagulopathies just problems with coagulation. 0:23:18.520 --> 0:23:19.520 Does that all make sense? 0:23:19.960 --> 0:23:21.119 Yeah, I'm with you. 0:23:21.520 --> 0:23:25.359 Pretty big picture, but pretty like logical. It's an assembly line. 0:23:25.440 --> 0:23:28.040 If you take out pieces, you don't get the final 0:23:28.080 --> 0:23:34.160 product mm hm to one degree or another. So how 0:23:34.160 --> 0:23:38.639 do you actually get this disease? Great question, Thanks for asking. 0:23:39.920 --> 0:23:43.880 We'll focus for this part on hemophilia A and talk 0:23:43.920 --> 0:23:46.760 also a little bit about hemophilia B because these are, 0:23:46.920 --> 0:23:51.000 of course the two classic forms of hemophilia. These are 0:23:51.000 --> 0:23:52.920 the two that people think of the most, and when 0:23:52.920 --> 0:23:56.640 you google hemophilia, that's what you get. So these are 0:23:56.680 --> 0:24:01.879 both genetic disorders, and both hemphilia A and hemophilia B 0:24:02.200 --> 0:24:05.639 are X linked recessive disorders. I don't think we've covered 0:24:05.640 --> 0:24:07.080 any of these, have. 0:24:06.960 --> 0:24:10.679 We, Eric, I don't think so. 0:24:11.359 --> 0:24:13.359 I don't think so. So this is kind of fun. 0:24:14.359 --> 0:24:17.960 X linked recessive just means that the genes that encode 0:24:18.000 --> 0:24:21.280 for these two proteins, factor eight and factor nine are 0:24:21.400 --> 0:24:25.639 found on the X chromosome. About fifty percent of the 0:24:25.680 --> 0:24:30.439 population only has one copy of that X chromosome, so 0:24:30.520 --> 0:24:34.159 they are more susceptible to this disease, more likely to 0:24:34.160 --> 0:24:36.679 get it because they just have the one copy of 0:24:36.720 --> 0:24:40.840 the X and if they have a mutated copy of 0:24:40.880 --> 0:24:43.800 factor eight or nine gene, then they're gonna have symptoms 0:24:43.800 --> 0:24:47.679 of hemophilia to one degree or another. If you have 0:24:47.760 --> 0:24:51.920 two copies of the X chromosome, then you most likely 0:24:52.240 --> 0:24:54.800 won't have any symptoms of disease, but you will be 0:24:54.840 --> 0:24:59.040 what's called a carrier because you have that mutated gene 0:24:59.040 --> 0:25:03.480 and can then pass it on to offspring. And this 0:25:03.560 --> 0:25:08.000 makes sense because I said that this was all a cascade, right, 0:25:08.880 --> 0:25:12.600 You only need a very little bit of factor eight 0:25:12.800 --> 0:25:16.760