DIP Episode 494 - Thalassemia and the USMLEs

Welcome, this is episode 494 of the Divine Intervention Podcast. And into this podcast we're going to be examining the fallacy. It's a high-yield topic for people who just don't know the USMLE. So I just want to make sure that you can have it down. So typically, let's not for the question. So what if they give you a question about a 10-year-old child, the children of this child, you know, looks pale, spends a brain to the office because he looks pale, and that he has been having like chronic right and left upper quadrant pain, and the children that he has abnormal contours to his face. And they give you a bunch of labs. Notice that the hemoglobin is pretty low. That's it, it's like six. And you notice that, wow, it's not just low, but the MCV is less than 80. So it's a micro-city canemia. And then you're told that the serum ferritin is pretty elevated. When you see something like this, and you're told that he has required many blood transfusions in the past, we see something like this, what should we be thinking of? I hope you're thinking about some kind of fallacy. So in this short podcast, let's go ahead and break down fallacy. It's a pretty important disorder to know and understand. But basically, we know that fallacy is the effect that a ton of people actually, or 280 million people worldwide have fallacy. And to understand fallacy, you gotta go back to hemoglobin. Hemoglobin is the thing that helps us carry oxygen in our bodies.

And as we know, there are two major types, right? I mean, there are two major globin chains in hemoglobin. Okay, let's maybe even go a little further down. So hemoglobin is made of hem and globin, right? And we know that hem is made in a certain pathway that you already imagine you've learned in biochemistry that has an earless synthase as the radiometeine enzyme. And then globin is just made, you know. And those globin, so we have a bunch of them. But the big ones are alpha globin and beta globin, right? So as you've learned, I've discussed this in previous podcasts before. But whenever you have anything that messes up your synthesis of hemoglobin, you're gonna have fallacy. Right? So if you have anything that messes up hem synthesis like lead poisoning, that's gonna cause you to have micro-city canemia. Or you have something that messes up globin synthesis like fallacy. That's gonna cause micro-city canemia. Or again, remember, hem is iron plus protoprofone. So if you mess up, if you don't have enough iron, you're also gonna have micro-city canemia for those reasons. So there are many causes of micro-city canemia. The big ones on exams, iron deficiency, lead poisoning. So iron deficiency, lead poisoning, thalacinias. Right? They're gonna see MC Vs under 80 for those cases. So since we know that, no more hemoglobin contains alpha globin and beta globin, that can then begin to tell us what the two kinds of thalacinias are.

And really, the two kinds of thalacinias are pretty straightforward. The alpha thalacemia is a beta thalacemia. I think for purposes of ease, we're gonna start off with a beta thalacemia first. But the critical thing to know is that all the thalacinias are inherited in an autosomal recessive fashion. Well, the beta thalacemia, we have two genes that go for beta globin. Literally, two genes. We pretty much have like one on each chromosome. In this case, there's gonna be chromosome 11 actually. That's a high-o thing. You just come into memory, especially for the step one folks. I don't know the whole chromosome 11 of business. So chromosome 11, the copy you have from your dad, you have one beta globin gene on that. The one from your mom, you have one beta globin gene on that. So if you have those things normal, then it's not a big deal. But if you lose one, if you have a mutation in one, then you're gonna have beta thalacemia minor. And they may be like, wow, the vine, that must be so bad. No, it's not really that bad. It's really not. Because at least you have one beta globin gene that's still helping you produce. So you're gonna be getting enough beta globits. But if you lose two, so usually if we would have lost one, they don't have many significant problems. They have like a mild anemia. Right? And I know lots of people are gonna see like target cells and whatnot, but whatever. But if you lose both, then you can potentially see how that can be a problem.

You literally have no beta globin whatsoever. Now, if you don't have beta globin whatsoever, that's problematic. It may be like, divine, why is that problematic? Or let me explain. First, normal hemoglobin is alpha 2 beta 2. If you don't have any beta globin, you literally cannot form normal hemoglobin, which we call hemoglobin A. So one kind of hemoglobin that will really rise up in these people is hemoglobin A2. Hemoglobin A2 in normal individuals is about 2.5 to 3% roughly of their hemoglobin. That's alpha 2 and delta 2. Notice it does not have beta globin chains in it. So since it doesn't require beta globin chains in it, and your body is gonna struggling with having beta globin chains, your hemoglobin A2 is gonna go up. And what other hemoglobin will go up in beta thalsemia? I hope you also seen divine hemoglobin F. Hemoglobin F is alpha 2 gamma 2. Alpha 2 gamma 2. That does not have beta globin chains in it, so the person is gonna be pretty good. How can you differentiate between beta thalacemia or minor, which is where you lose one gene and beta thalamage, which is where you lose both genes. Simple. Again, you don't have to memorize any of these things. Just try to understand, I'm gonna try to go slowly so you can understand it. In beta thalaminer, you're still gonna have some hemoglobin A, because at least you're making some beta globin. You're gonna have some hemoglobin A, although you'll be reduced compared to the normal adult.

You're gonna have an increase in your hemoglobin F. That's alpha 2 gamma 2, right? Because that doesn't have beta globin chains in it. You're gonna have an increase in your hemoglobin A2. That's alpha 2 delta 2, right? And again, those are gonna have like minor amymia, they make me completely symptomatic. Now, if a person has beta thalamager, where they literally have no beta globin at all, they will have no hemoglobin A at all, because they have literally no beta globin. They have, they have no hemoglobin A at all, right? That's very important to understand. That's a very critical difference from beta thalaminer. They'll have no hemoglobin A, because hemoglobin A is alpha 2 beta 2. If you're in a beta change, you're not gonna have any hemoglobin A. They're gonna have an increase in their hemoglobin A2, right? So, alpha 2 delta 2, they're gonna have an increase in their hemoglobin F, alpha 2 gamma 2. It's very important to keep in mind and those people tend to have pretty significant amymia, pretty significant amymia. Now, how do we, okay, I guess I'll talk a lot of treatment of thalamcinia as a general in a bit. But I wanna deal with the molecular basis of both and then we'll kinda go from there. So, again, remember, hemoglobin, I mean, beta thalamcinia is a chromosome 11 in short. But let's go into alpha thalamcinia. Alpha thalamcinia is also a disorder assessive. Well, this is more of our chromosome 16 problems, more of our chromosome 16 problem.

So, here you have four genes, four genes, four genes, four genes, right? You have two in each chromosome from your parents. So, you have two on that chromosome 16, two alpha genes, and you have two on chromosome 16 from your mom. Now, since you have four genes, you can already begin to see that, oh, there's more disease permutations. Now, what are the disease permutations to know? Well, number one is, let's say you lose one alpha, let's say you lose one alpha-globing chain. If you lose one alpha-globing chain, it's not a big deal. You're gonna pretty much be asymptomatic. If you lose two, honestly, for the most part, you're also gonna be asymptomatic as well. Yeah, you may have a mild amymia, but it's not a big deal. You literally still have 50% of your genes kind of working for you. I almost like to think of that as like the, you're like, oh, I've lost three, because remember, a beta-thalminer. You've lost 50% of your beta-globing. Right? So, you've lost 50% of your alpha, this is not a big deal. The only thing I'll say to know about these alpha-business, I mean, this losing two genes business, is especially on the US-Milister point exam. You love to see if you can epidemiologically tell the says from the trans problem, right? So, remember, I said that you have two on your, that's chromosome 16 and two on your mom's chromosome 16. If you knock out both on one chromosome, let's say you lose all two from that, or you lose all two from mom, that's a cis deletion.

It's actually pretty high, you know, it's pretty common in Asians. It's pretty common in Asians. Pretty common in Asians. And then the trans deletion is where you lose one from that chromosome and one from mom's chromosome. That's tend to be far more in Africans. The thing is if you compare both, again, I wouldn't worry too much about the prognosis of both, but in general, if you lose, if you have the cis deletion, it tends to be a bigger issue and the trans deletion. But again, not a big deal. So again, don't sweat it with regards to the difference in prognosis, cis trans is largely the same, right? If you have a two-gen deletion, it's not a big deal. Now, the most critical thing to know about the cis versus the trans is that, for cis, is we tend to find you more in Asians, trans, we tend to find you more in Africans. That's it. Just a little bit of that. Okay, just a little bit of that. Okay, so now, if you have a three-gen deletion, okay, so that's where cis that get interested. Because we have a three-gen deletion, you have pretty much lost 75% of your genes, right? So that's problematic. Now, for these people, you know, there's still going to be making of, you know, hemoglobin A, alpha 2 beta 2, but it will be vastly decreased. There's still been making hemoglobin A2, alpha 2 delta 2, but again, it's going to be vastly decreased, because they have a shortage of hemoglobin.

There's still going to be making hemoglobin F, alpha 2 gamma 2, but again, that's going to be vastly decreased. But one thing to kind of keep in mind, is that you have this problem, is since, since you, when you have these three alpha-gen deletions, since you have very few alpha, so you have way more beta. The thing that's going to happen is that the beta is I don't want to stop pairing up with each other. So you have something like beta 4. Beta 4 is what's known as hemoglobin H. Hemoglobin H is literally beta 4. That's why sometimes when you've lost all three alpha-globin chains, we call it hemoglobin H disease. Hemoglobin H disease. It requires a lot of transfusions. They tend to be more symptomatic. And one thing I'm going to say is that people that have this alpha-phalacemia, especially if you put a half hemoglobin H disease, you may actually see, so you'll see target cells like you see for phalacemias, it's going to be a micro-city cademia. But you may actually see Heinz bodies as well, right? You may actually see Heinz bodies. So these hemoglobin H dot precipitates within the red cell and confirm a Heinz body. So just be careful. Heinz bodies are not only found in G6 pd deficiency. You certainly can find them in the phalacemia, especially like the alpha-phalacemia, just FYI, especially the most severe forms of alpha-phalacemia. And then obviously the one that's the worst of the worst of the worst is going to be where you've lost all four chains.

We've lost all four chains. That's really bad. So people, when you've lost all four chains, you literally have no alpha chains, literally none. So are you going to be able to make hemoglobin A? No. That's alpha-2 beta 2. You don't have it. You're going to be able to make hemoglobin A2. No. That's alpha-2 delta 2. You literally have no alpha-globin chains. Are you going to be able to make hemoglobin F? No. Alpha-2 gamma 2. You literally don't have any alpha chains. So what are the options you have? Well, people that have the forging deletion one, they can have a hemoglobin H. Because again, remember, hemoglobin H is beta 4. You have no alpha. So what do you have beta? So what do you have beta? So what do you have beta 4? That's hemoglobin H. So again, these people can also have Heinz bodies. But think about things from a more in uteru perspective. From one uteru perspective, right? In uteru, you need alpha-2 gamma to hemoglobin F. They have no alpha. So they're going to be able to make hemoglobin F at all. So those gamma, since there's a ton of it while you're in uteru, the gamma is going to stop pairing up with each other. You're going to form gamma 4. Gamma 4, that's hemoglobin bar. That's hemoglobin bar. Hemoglobin bar. It's not very compatible with life. So many of these kids are either going to die in uteru or right after they are born, they're going to be dead. That's the critical thing to know about hemoglobin bar.

So if you see a child that has thalasemia and the diuter or the di-chust right after birth, they have the 4 gene deletion from an alpha-globino perspective. So again, oh, divine. How can I differentiate between the 3 gene deletion and the 4 gene deletion for alpha thalasemia? Simple. In alpha thalasemia, the one way you've lost all 3 genes, you're going to have a decrease in hemoglobin A. Decorise the hemoglobin A2. Decorise the hemoglobin F. And I'm increasing hemoglobin H. Right? But we would have the 4 gene deletion. They're going to have no hemoglobin A, no hemoglobin A2, no hemoglobin F. They'll have hemoglobin H, and they'll have a hemoglobin bar. Right? That's the gamma, gamma 4. Okay. So I guess the big thing is, if a person has thalasemia, how many you make the diagnosis? If you're so spectacular, the very first thing you're going to do is you're going to go to a complete blood count. That's many times going to be the right answer on the USMELIS. You're going to get a complete blood count. And after you get that complete blood count, you're going to see anemia, blah, blah, blah, blah. And many times it's good to get a peripheral blood smear as well, while you're doing that complete blood count. You'll see the target cells. Again, if you see those high-ends bodies, that should tell you that, oh, wait, I'm probably doing alpha thalasemia, where these folks have lost 3 or 4 of those genes. But then after that, you're going to do some more specific testing.

You're going to be hemoglobin electrophoresis. It's something we tend to do more for beta thalasemia than for alpha thalasemia. He won't be an electrophoresis. It's just something that's done more for beta than alpha. So I would not think of it as a way you want to diagnose alpha thalasemia, you exempts. Think of it more or something you want to do for beta thalasemia. So some of you may wonder, what are some of the symptoms, personally, see when they have these thalasemias. They can actually see a bunch of symptoms, right? So one, you may notice that they have these chipmunk faces. You may wonder, define what's the mechanism there. They may have chipmunk faces. They may have hepato megalith, they may have spinoe megalith. They may have all those bone-being, brittle bones. What causes that? Well, the thing that causes that, I want to know for you, exams, is extramedulary hematopoices. Extramedulary hematopoices, right? Because these red blood cells are pretty defective that I made. So your body just destroys them quick. So you're always making as much hemoglobin as possible, as much hemoglobin as possible, as much red cells as possible. So you're not going to just leave it to the bone marrow. You're going to make it in any other place. You can make it itself. So you can keep up with the demand. So you're going to make it in the spleen, you're going to make it in the liver, you're going to make it in your bones, right?

That's why you have like that, those chipmunk faces, you have the hepato megalith, you have the spinoe megalith. And also, another thing that stimulates these people's red cell production, believe it or not, is that when you have these anemias, the oxygen-carrying capacity of your blood literally plummetes. Because you're going to have a lot of blood, literally plummetes. Because remember, hemoglobin is like the boss that carries oxygen around here, but if you're oxygen-carrying capacity plummetes, then your tissues are going to be hypoxic. That's going to cause your kidneys to make a ton of epo. So epo is going to keep grinding, stimulating a ton of red blood cell production, right? So those are the two reasons why they may have all this extramedularia hematopoesis. It's actually pretty high yield to know. And again, hepato megalith, it may be because of extramedular hematopoesis, although one of the big reasons they get this spleen or megalith business is that over time, because the spleen is just destroying, because the spleen, I like to think of it as like the quality control red blood cell region in the body. So it looks like red blood cells, do they look quality to do not look quality? No, no quality is going to destroy them. So because a lot of red cell destruction and production is happening in the spleen, the spleen is going to get huge, huge, huge, huge. And that's certainly going to cause, certainly going to cause the problems. Certainly going to cause problems.

So just something you want to keep at the back of your mind, for example. So that's why they may have a hepato megalith, that's why they may have spleen or megalith. And the thing is, since they are making so many red cells all the time, they are bone marrow just expands. So it's almost like your bone marrow has bone and marrow. But if the marrow part, because you're making some red cells, just sticks over the whole apparatus, then the bone is going to be less and less and less. So this look and have brittle bones. They have a pretty high risk of osteoporosis. That's an essential, certainly want to know for you, exaps. And then another association you want to know is, you want to, if they tell you that, well, you see like creatinine percorjone, pitone, fever, and one of these folks, it's because they have a coulissusitis. Why, what's the mechanism there? Well, again, think about it. You're always breaking down red cells. Always breaking down red cells. That's going to make a ton of indirebularbin. Because you make a ton of indirebularbin. You're not just making a lot of all these bilirubin, ghost bones. So you have a very high risk of these bilirubin-related issues like, you know, coulissusitis, coulithitis, biliricolicone, and things like that. And you may see divine. You know, you said that the one that tends to kill people in uterus or the direct after birth is the, when you have the four-offer gene deletion, four-offer thalacemia, yes. That's absolutely the big one.

Because they can have high drops of italus. And many people always struggle like divine. What in the world do you mean by high drops of italus? Well, let me explain. Let me explain. So, say, for example, you have the alpha, the four-offer gene deletion. So you don't have any hemoglobin A, no hemoglobin A to no hemoglobin F. Hemoglobin F is like the big, big, big hemoglobin we need in uterus. But you don't have hemoglobin F at all. So you're going to start doing these gamma-force, hemoglobin B. Now, why do you think that hemoglobin B is bad? Well, think about it. You already know this from your studies that hemoglobin F has a higher affinity for oxygen, compared to regular hemoglobin, compared to regular adult hemoglobin A. It has a higher affinity for oxygen. If you have a higher affinity for oxygen, are you going to be delivering oxygen to the tissues? No, you're not going to be doing any of that. Now, think about this. When you imagine you have hemoglobin B. Does not just have two gamma, because remember, fellow hemoglobin is two-offers two gamma-ers. No, now you don't have two-offers two gamma-ers. You have four gamma-ers. That has an even higher oxygen affinity than hemoglobin F. Literally, hemoglobin B has super, super high affinity for oxygen, compared to hemoglobin F. And also, hemoglobin B is that beta-4, also has a super, super high affinity for oxygen, compared to hemoglobin F.

So you have a bunch of the predominant hemoglobin in these fetus, or hemoglobin that have a high affinity for oxygen. So since they have such a high affinity for oxygen, they're not going to be releasing oxygen to the fetal tissues. So there's going to be a lot of fetal hypoxia. There's going to be a lot of fetal hypoxia. And that fetal hypoxia, what do you think he's going to do? Well, it's going to do one big thing. It's going to put your heart under pressure. Because the tissues in the fetus are telling the fetal heart. We want oxygen. We want oxygen, we want oxygen. The fetal heart is like, okay, fine. I'm going to make the blood going around the body more often. If the blood goes around the body more often, that will probably help. So the blood starts going around the body more often, because again, you're oxygen-carrying capacity, so your heart is always pumping, pumping, pumping, pumping, pumping, pumping, pumping, pumping, pumping, if your heart is always working that hard, one of these is going to fail. That's literally what's called high output heart failure. Because remember, your heart is a muscle, right? So you have heart failure because your heart is working at chronically elevated cardiac output. That's literally what high output heart failure is. Over time, the heart will fail. When the heart fails, you're going to have a build-up, right, or fluid in the lungs, the right heart will then fail.

And then you're going to have a build-up of fluid in the body, right? You're literally having an increase in hydrostatic pressure within the body. That's going to cause hydrops fatalis. Hydrops, right, means you're hydropic. That's fluid. Hydrops fatalis in the fetus. Now, another mechanism behind the hydrops fatalis that, again, many people do not kind of give credit for it, is this, right? So again, remember I said that one of the things that happens in phylasemias is you have like extramedulary hematopoesis. Yeah, absolutely. You have extramedulary hematopoesis just to keep up with the constant making of right cells. And again, I've discussed the reasons why you need to keep making these red blood cells. So, since the liver becomes a side of extramedulary hematopoesis, the liver is like struggling. It's like working hard on something that normally does not work hard on, which is making right cells. So, think about it this way. If your attention is divided, then things you're supposed to give very good responsibility to time and attention to you don't. So, one of the things the liver does not give as much time and attention to, when it's so preoccupied with making right cells in extramedulary hematopoesis, is albuming. Your liver stops making adequate amounts of albuming. Do you see my story there? If you're not making adequate amounts of albuming, surprise, surprise, guess what's going to happen to you?

You're going to have a decrease in uncorrect pressure in your vasculatory. And if you have that decrease in uncorrect pressure, you're not going to be keeping fluid within your vasculatory. You're going to have more fluid extroversiation because of that decrease in uncorrect pressure. That's going to cause you to become a demodus. So, again, the two mechanisms behind hydroxyetyl is one is a decrease in uncorrect pressure and an increase in hydrostatic pressure. I'm going to target it to mechanisms. Honestly, like the more I talk in this podcast, I'm like, wait, this podcast is pretty nice because there's a lot of mechanistic things that you can learn. Honestly, I love him, hematology for this reason. Most things can be risen down through mechanisms. But, anyhow, let's keep going. So, hopefully you understand the two major types of phalacemias. The one thing I'll comment on is, before I talk about treatment, the one thing I'll comment on is this beta phal in intermediate. Some resources kind of stress it. I wouldn't worry too much about it if I were you, honestly. But the big thing about that is that those people have compound heterosigotes. So, they don't have the situation where, wow, both beta-glubing genes are completely trashed. No, it's like, both beta-glubing genes have like partial functions. So, they're kind of like intermediate. They're kind of in the middle. They're compound heterosigotes. Again, how do sweat too much about that if I were you?

So, again, remember, put off phalacemias. You're going to see target cells on a blood smear. When you have that 304-alpha glubing gene deletion, you're going to see high-end bodies as well. And this is about going to have a microsylicia andemia. So, the MCV is going to be less than ED. Again, remember, this will can develop jundes because of an increase in inter-rebelly-robin. And, obviously, because the arat cells just keep getting broken, right? Again, that's going to cause that indirect hyperbular reninion. So, how in the world we treat these people? Well, the thing is, if you have the asymptomatic, you don't have to do anything. But, if they have symptoms, they're going to need blood transfusions. They're going to need blood transfusions. Well, think about it. When you're given a person a blood transfusion, you're literally giving them iron. Blood, literally one of the biggest components is iron. So, you're giving them not just blood, but you're giving them a ton of iron. That iron can begin to cause iron overload, right? And iron also depositing people's like levers and damage it. Think of like hemochromatosis, right? You can develop liver failure. You can develop pancreatic failure, right? Because the iron fencing reaction for your other cool production damage your pancreas. You can also damage these people's pituitary glands, right? So, that can cause all these problems. You can have iron overload.

So, many times, people that have phalacemias, in addition to the blood transfusions, you're going to put on iron-kileter therapy, right? So, something like deferoxamine or deferoacerox, or defereperon, right? Differoxamine is spelled D-E-F-E-R-O-X-A-M-I-I-N-E. That's an amine. I probably remember that from O-Cab. Anyhow, deferoacerox, right? Defereroacerox is spelled D-E-F-E-R-A-S-I-R-O-X. Defereroacerox. And then defereperon is spelled D-E-F-E-R-I-D-P-R-O-N-E, you know, like being prone to something, right? So, you're going to use those iron-kileter so I can develop iron overload. And then, if those things are not controlling their symptoms, in addition to that, one thing you can use is hydroxyoriac. Hydroxyoriac is actually pretty helpful in phalacemia, because what does it do? It jacks up your hemoglobin F. It jacks up your hemoglobin F. Having more hemoglobin F is very helpful in people that have alpha-phalacemia or beta-phalacemia. Right? Raise those people's hemoglobin F. Raise your hemoglobin F. It's going to be very helpful for those folks. It's going to be extremely helpful for those folks. Extremely, extremely, extremely helpful for those folks. Okay, so something you want to keep at the back of your mind for your test. And also, this push would also get full-lit supplementation, because again, they are itself, they just use them up so quickly. So they are always like in ribloxel production mode.

Remember, you have only about three months worth of full-lit in the body, right? But this will just use of their full-litzoquic. So they need consistent full-lit supplementation. And then, if you see like this massive precipitose drop in a phalacemia patient, you see a massive precipitose drop in there, hemoglobin. They have this acute anemia. And they tell you that, oh, they had like a viral URI recently. Think of a parable-be-19y plastic crisis. A parable-be-19y plastic crisis. And then remember, one method you may use potentially to cure phalacemia is to do a bone marrow transplant. It actually works pretty well if you can find the right match. You can do a bone marrow transplant. And then I think one final thing I want to say is that people that have actually maybe two final things. You tend to find phalacemias in people from the following countries on the exam. People from Greece, people from Italy, Middle Eastern populations, South Asian populations, and Africans, right? And sometimes they can also put this in Turkish people. But again, just kind of keep that at the back of your mind as you study. And remember, it also kind of kind of having phalcemia, especially like the more minor ones, like the beta and alpha-thal miners, kind of reduces your rate, has some protection against the malaria. So that's something that may be helpful to you to keep in mind. Okay, I think I'm going to go ahead and stop here.

Again, I know this may be called a phalcemia podcast, but man, if we talked about a lot of different mechanisms. So this is a pretty close podcast to know about. So I'm going to stop here. Again, offer review classes for step one, I have a 25-hour class coming up in early January. And then for step one to step three, I'll offer a 2.5 hour in-be-imitistic in-class a 4 hour bio-stats class. Five hour social science is quality improvement, ethics and communications and healthcare systems class. And then for step two, step three itself and shelf exams have a 20 hour step two class, a step two step three class. And then I have a one, that's actually coming up about two weeks from now. These other classes I said that one and a half hour in-be-imitistic in-class, that's actually taking place next week. So if you're interested, just shoot me an email. And then I also have a 100 hour super comprehensive step two, step three review. It's going to be taking place in May of 2024. If you're interested in any of them, just shoot me an email. I also offer one or one to learn for all the US Emily exams and med school exams. And then I have these podcasts on Apple Google on Spotify, I have a You Tube channel, Divine Intervention, US Emily podcasts and videos. And then I have another website called Divine Intervention Life Lessons.com. Every week I try to post like two podcasts where from a biblical perspective, I try to address a life lesson.

And there's actually an Apple podcast associated with that. But again, thank you for listening to me today. And for one of our somebody, God bless you. I'll see you next time. Bye for now.

Target cells (and sometimes Heinz bodies).

Hemoglobin A2 ($\alpha_2\delta_2$) and Hemoglobin F ($\alpha_2\gamma_2$).

Hb Barts disease (or $\gamma_4$ polymerization), leading to neonatal crisis.

Extramedullary hematopoiesis (EMH) and chronic hemolysis/red cell destruction.

Iron overload, leading to potential liver or cardiac failure.

Cis deletion (losing both genes on one chromosome).

Alpha ($\alpha$) and Beta ($\beta$).

Chromosome 11.

Minor shows elevated HbA2 and HbF; Major shows severely reduced or absent HbA.

Hemoglobin H ($\beta_4$).

Fetal hypoxia caused by highly oxygenated hemoglobins (like Hb Barts) failing to release oxygen to tissues.

Deferoxamine, Deferasirox, or Deferiprone.

Alpha ($\alpha$) and Beta ($\beta$).

Chromosome 11.

Minor shows elevated HbA2 and HbF; Major shows severely reduced or absent HbA.

Hemoglobin H ($\beta_4$).

Fetal hypoxia caused by highly oxygenated hemoglobins (like Hb Barts) failing to release oxygen to tissues.

Deferoxamine, Deferasirox, or Deferiprone.