DIP Episode 85 - USMLE Step 1 Hematology Review Part 6 (Final)

Okay, welcome. This will be the EDI fifth episode of the Divine Intervention Podcast. My name is Divine. I am a PGI-1 transitional year resident that's ultimately going into radiology. So into this podcast I'm going to be finishing up a discussion of He-Monk for the USML Step 1. So this will be part 6 and this will be the final part. So we'll be done with, we can finally close the chapter on He-Monk. So really, today's proposal is just to clean up certain things I haven't talked about. This should hopefully not be a long podcast. Right? And the first topic I'll start with, right? What if you get a question about a person that's, you know, nothing European ancestry and then they give you like a history of like anemia in that, grandma, grandma, whatever, like basically a genetic history. If you see that, you really want to think about a heritage research like Tosis, classically on exams, right? They will tell you the person is from like another European country. And remember, there is a scene that genetic history is that it's actually inherited in an orzoid dominant fashion, right? And basically, the mechanism behind heritage research at Tosis is that you have mutations in certain proteins, proteins that constitute the cytoskeleton of red blood cells, right? And to be honest with you, you actually do want to know the names of these proteins, right? So there's proteins like spectrin. There's andaone known as anchoring. There's andaone known as band three. Okay?

There's one that's lower yield. They call it like protein 4.2, but that's beside the point, but band three, you definitely want to remember. You may see divine. I've never seen that shop on an exam. Think again, okay? Think again. So band three, spectrin and anchoring, those are like the big ones you definitely want to know, right? So how do you make the diagnosis of heritage research at Tosis? I mean, obviously, right? If you look at, if you look under the microscope, right, for these are spherosites. They're basically like red blood cells that lack central palarine. They're very tiny, right? Because it's like, because they have all these like membrane protein defects, you essentially have a fixed amount of hemoglobin that's crumpled into a smaller space, right? So if you expose that spherosites to a hypotonic solution, right? That cell will explode, right? Because in the cell, in the presence of a hypotonic solution, water will flow into the red blood cell and that cell will explode. That's what's actually known as the osmotic fragility test. That's one test that can be used for the diagnosis of heritage research at Tosis. Another somewhat similar test is called the acidified glycerol lysase test. You basically add acidified glycerol to like a hypotonic solution containing the spherosites. And again, that will cause an abnormal, an abnormally elevated amount of himolysis, right? It's kind of similar to the osmotic fragility test.

And then, remember that band 3 protein I talked about? There is actually a protein. There is like a fluorescent protein that has the ability to bind band 3. That protein is actually known as eosin-5 malemite. So that's actually what constitutes the eosin-5 malemite screening test for hereditary spherosytosis. And I mean, obviously, if you do a red blood cell studies, the classic thing, remember, I talked about this in this, I talked about it in the podcast actually I believe from yesterday. I said that your MCHC is increased in the setting of hereditary spherosytosis. That's a big, big thing you want to know. And really, the way you trade this, because for the most part, the spherosites are not a huge issue. The problem is they get trapped in the spleen and the spleen destroys them. So if you actually do a spleenectomy, you can actually go ahead and treat hereditary spherosytosis that way. But remember, before you take out that spleen, you want to vaccinate it against shinolysm, so like strep pneumo-h-flon-my-seria, because remember, your spleen helps you protect you against encapsulated bugs. And really, these patients with hereditary spherosytosis, because they are having all this himalosis, and they are forming all this bilirubin. They actually have very high risk of like gallstones, right? So like polythiasis, usually like the pigmented kind. So I think that's all I'm going to say about hereditary spherosytosis.

Again, it's a high yield disorder to know shows up on all the USMLE's super, super high yield to know. So I guess, and I mean, one thing I guess I can go ahead and mention is that hereditary spherosytosis, it's usually a kind of hemolurecanemia that's cum's negative. I'll talk about the cum's test star, about the cum's test star in a bit. It's just one of those weird bizarre things you want to know. I'll sort of talk about the mechanism in a short while, right? In fact, you know what? Let me go ahead and talk about the cum's test now, because it's kind of important to know, right? So the thing is, there are two kinds of cum's test, right? So there's the direct cum's, and there's the indirect cum's. Now, there are two things I think are most important to know with the cum's test. The first thing that's important to know is you want to know the mechanism behind each cum's test, and then you want to know the indications for each cum's test, right? So there's a direct and indirect, let's talk about the direct first. So for a direct cum's test, the thing you try to do, right? The indication for a direct cum's test is basically to test for the hemolurecanemias, okay? You'll test for the hemolurecanemias with a direct cum's test. Now, for the indirect cum's test, you use it to basically screen a patient's blood for antibodies before using that patient's blood in a transfusion process, right? So let's talk about the direct cum's test.

I said you use it to scream for the immune mediator hemolurecanemias, right? So basically let's think about this for a second. The direct cum's test, if a person has like a hemolurecanemia, the thing that happens is that their red blood cells are coated with antibodies, okay? That's, and the antibodies can be IgG, that'll be like the warm autoimmune hemolurecanemia or IgM in the setting of the code autoimmune hemolurecanemia, right? So if your red blood cells are already coated with antibodies, the thing you can do is you can basically have a solution that includes those red blood cells that are already coated with the bad antibodies, and then you add anti-globulin, right? That anti-globulin is known as Homes reagent. If you have aberrant antibodies on the surfaces of red blood cells, then you have a glutination of those red blood cells, and that's a positive direct cum's test, okay? That's a test for autoimmune hemolurecanemias. Remember, you autoimmune hemolurecanemias, like I said, there's those that are IgG mediate, right? Those are the warm autoimmune hemolurecanemias, and I mean, those can be caused by many things, right? They can be caused by, you can observe those in the setting of lupus, right? Remember lupus can have like autoimmune anemias as like a sequely of a lupus. Another classic example presentation is with certain drugs, right? So like alpha-method lupus, remember, it's that drug that's associated with drug-induced lupus, right?

So you see that lupus association again, that's associated with drug-induced lupus, but it also is very good for the treatment of hypertension in pregnancy. It's a large molecule, so it doesn't cross the placenta as well, okay? So it's one of those anti-hypertensives that are safe in pregnancy. Alpha-method lupus, very good for the treatment of, for the treatment of hypertension in pregnancy, but it's associated with autoimmune hemolurecanemias, especially the warm autoimmune hemolurecanemia. Another classic drug that's associated is like your cell wall synthesis inhibitors, right? So like your beta lactams, like your penicillins, your cephalosporins also have that association, right? So again, autoimmune hemolurecanemias, the warm kind, the IgG-meditated type, think about those in the context of drugs, okay? And also lupus. Now, the cold autoimmune hemolurecanemia, that's usually associated with like IgM, okay? And usually those patients will present with like Reynolds phenomenon on an MBN exam, right? And the thing is there are certain bugs that actually have that association with an IgM-meditated cold autoimmune hemolurecanemia. Classically, it's like microplasma, okay? I remember microplasma is the thing that causes like atypical pneumonia. In fact, it's very high, you have to know this microplasma pneumonia is the most common cause, very high, or it's the most common cause of atypical or walking pneumonia, right?

So if you see like, in testically infiltrates on imaging, and the patient that's not immunocompromised, especially in a person that's between the ages of 20 to 40, you really want to think about microplasma pneumonia, and it's associated with the IgM or cold autoimmune hemolurecanemia. And in the same bar virus also has like a weak association, but I really want you to think more about microplasma and pneumonia, right? So this represents an example of a disease condition that has a bog association, right? So I guess think of it as like a hematologic disease that has a bog association, right? So if you remember, I talked about a Pofyrcutinia tarda in the podcast from either yesterday or this morning, and Pofyrcutinia tarda has an association with HEPC, okay? But cold autoimmune hemolurecanemia has an association with EBV and microplasma. Microplasma is the stronger association. And again, you will test for these disease with the directs cum's test, okay? Now, the indirect cum's test, I say you use it to screen block to see if it contains a nasty, nasty, nasty antibodies, right? That may react against a person's blood that basically against a person that you're giving a transfusion, right? So take for example, if you're giving, let's say you have person, let's say you have person A, okay? Person A needs blood, okay? And person B is the donor. So keep it straight, you can probably write this down. Person A needs blood, gonna get transfusion.

Person B is the person donating the blood. The thing is, you want to make sure that person A's blood does not contain antibodies that will react against the blood he's getting from the donor person B, okay? So the way you test for the presence of antibodies in person A's serum is with the indirect cum's test, right? So I give you an example, right? So in fact, let me just sort of walk through it, right? So the thing that happens is the person that's receiving the blood, right? Person A, you go ahead and pull out the arrayed blood cells from the plasma, right? Because all you care about is do they have antibodies that can react against the blood they are going to receive from this donor, right? So you are actually not testing the arrayed blood cells, you're actually testing, you're actually testing you're actually testing the serum for the presence of a body antibodies, right? So you strip of the strip of the arrayed blood cells of the person receiving the blood, right? So the recipient of the blood transfusion and then you take the serum, okay? And when you take the serum, you mix it with a small portion of the blood that they are about to receive, okay? And then after you do that mix, you then add the anti-globulin, okay? Like the cum's reagent.

And if you have a glutination, then that tells you that you are dealing with, that's the same, that tells you that, okay, this person that is receiving the blood transfusion, person A, so the recipient of the blood transfusion has antibodies that will have a bad reaction against the blood they are receiving from the donor, that's a person B, okay? So again, high-youtone, I know it's subtle, but it's actually super, super, super, super, super, super high-youtone this. In a direct cum's test, you are checking for antibodies that are already bound to the red blood cell membranes, okay? And you use that in the setting of auto-immune hemolytic anemias to test for those autoimmune hemolytic anemias. Contrast that with the indirect cum's test, okay? That is used that essentially detects antibodies that are not bound to red blood cells, but antibodies that have the potential to bind to red blood cell membranes. You find them more in the serum, okay? That's why it's called an indirect cum's test. And that's why you have that mixing procedure that happens before the test occurs, okay? Again, subtle, if you need to rewind this to listen to it, I highly encourage you to listen to this. It's just one of those things, I can almost promise you'll see on step one, you'll see on some shelf exams during your third year, and you also see on step two as well, okay? And also potentially on step three, very high yield to understand this. So now that we're done with the cum's test, right?

We can, I guess, talk about like some, you know, some classic patterns of hemolysis, right? So you can see people having some you've, you've heard me refer to this in prior hematology podcasts where I talk about like intravascular hemolysis and extravascular hemolysis, right? The thing is extravascular hemolysis is something that occurs basically like in the spleen, in the bone marrow, and in the, um, can also create the liver, right? Basically macrophages, the gobble-up red blood cells, and then when they gobble-up those red blood cells, they basically explode them, and when you explode those red blood cells, then the person gets, uh, the person gets, uh, like an un-conjugated hyperbularibinemia, and then goes through that whole process that I believe I already described in the, in my biochemistry video. So, um, in travascular hemolysis, something that happens in the spleen is actually a lot more common than in travascular hemolysis, okay? And the key thing again, you want to know is that it occurs from macrophages that are in the reticulo-induthylial system, like the spleen, like the liver, like the bone marrow, okay? Now, contrast that with intravascular hemolysis that is actually less common, but certainly still happens, okay? Intravascular hemolysis literally occurs intravascularly, it occurs inside the bloodstream, okay?

And usually, the, certain things that can cause intravascular hemolysis, I think it's like paroxysmone, nocturnal hemoglobinuria, that's a relatively common cause of intravascular hemolysis, although I'll say that in general, intravascular and intravascular hemolysis tend to occur together, okay? But a pathonomonic finding in the setting of intravascular hemolysis is something known as, uh, is a, uh, is a phenomenon where your haptoglobin is severely decreased, right? So, if they give you an exam question and a person has like red urine from like hemoglobinuria and whatnot, and they tell you that their, their haptoglobin levels are super low, you really, really, really want to think about, um, and in intravascular hemolysis, that is arising, um, in the setting of, um, uh, like some kind of, uh, hemolytic process like a paroxysmola, nocturnal hemoglobinuria. So, um, so, I'm trying to think, is there anything I really want to say about this? Oh, actually, I do. There are some other high-yield things I want to say, right? So, I said that intravascular hemolysis, um, PNH is a classic example. DIC, so disseminated in intravascular coagulation, is another classic NVME exam cause of intravascular hemolysis, right? So, remember, in DIC, you observe, uh, schistocytes. In fact, if you see schistocytes in an NVME question, that should lead you more towards intravascular hemolysis versus extravascular hemolysis.

So, schistocytes and a decrease, one, undetectable hub to globin, that tells you that you're dealing more with intravascular hemolysis, okay? And usually, those people tend to have like red urine and their kidneys also kind of look red, right? Because again, all that hemoglobin that's like speared into the circulation just basically goes to the kidneys and is, uh, got in rid of through your urinal, urinal system. And, um, I think that's all I really want to say about intravascular versus extravascular hemolysis. Um, again, that hub to globin relationship and the schistocytes that you find in intravascular hemolysis, that's probably like a very useful delineating factor between those two. But extravascular hemolysis for the most part is a lot more common than intravascular hemolysis. And I mean, I've been talking about intravascular hemolysis and talking about a PNH, uh, paroxysamol, an octanol, a hemoglobinuria. Um, again, I sort of kind of talked about this, um, earlier on, I believe I talked about this either yesterday, yesterday's podcast or the podcast I meet this morning. But basically PNH, right? It's, uh, it's not a great disease, but the classic way it presents, it will present in a young person, okay? That is having like weird thrombotic episodes, right? So they can have like thrombosis of like a mesenteric artery or thrombosis of like, uh, they just, they just basically have like, like, they can have like hepatic artery thrombosis, like really weird thrombosis.

And then they also have like red urine and then they have a hemolytic anemia. If you see that triad, you really want to think about paroxysamol, an octanol, hemoglobinuria, right? And the thing is, it basically arises when a person has like a PGA mutation. I mean, if you sort of crumble the words PGA, you can get out the word GPI anchor, okay? So you have like a PGA gene mutation, when you have a PGA gene mutation, you essentially, um, lose, uh, the gene that helps you produce certain, like, sticks. So like, certain proteins that help you hoist things like CD55. I believe CD55 is known as, uh, DCH Xelerating factor and CD59, um, that essentially protects your red blood cells from, uh, from hemolysis, right? So I mean, CD55, I would hopefully in the future, have an immunology podcast, but the thing is CD55 essentially prevents, uh, like, C3 convertase from forming. And if you don't form CD3 convertase, right? Um, um, then you will not lie your red blood cells, but if you're obviously, um, lacking, uh, CD55, then C3 fragments will sort of build up on the surfaces of your red blood cells. And then through like the alternative or complement cascade, they will lie your red blood cells under those circumstances. Um, CD59, right? It's like the thing that, if you remember from, uh, acolyzium that I talked about in this morning's podcast, um, with like my cereal, sepsis, you need C5 through C9 to form the membrane attack complex.

And the thing is, everyone needs to be present for that membrane attack complex to happen, right? So the thing that occurs is that, um, um, uh, CD59, it's normal job is to bind to C9 and prevent it from associating with a C5 through C8. So you end up not forming that membrane attack complex, right? So if you're lacking CD59, you have, um, C9 binding to its C5 through C8 bodies. And then you're running to trouble relatively quickly with the membrane attack complex that essentially explodes your red blood cells, okay? So that's, those are the two mechanisms behind the himologies that are observed in Paroxysimal, notional, hemoglobinuria, okay? So how do you test for P&E? Trilogy, the way you test for it is, um, you can, um, do something called, uh, uh, uh, I mean an O test, uh, that you may still see on the USMLE, it's called like the ham test. Sometimes people call it the, um, uh, in fact, let's just, let's just, let me know completely things too much. It's called the ham test. You basically have CDFI solution and you notice that the person's red blood cells explode at higher than normal rate than, uh, normal like control or red blood cells. If you see that, you're thinking about, um, P&E, right? And the reasoning behind that is actually acidity, um, increases the propensity of complement to lice cells that it is bound to. In fact, one of the proposed mechanisms behind the, behind the, uh, red urine that's found in the presence of P&E.

I mean, one probably that's more correct is that, oh, when you get up in the morning, your urine is more concentrated, so you see like your urine appears like red. But another thing people think about is that if you really think about it, right, when you sleep, right, you don't breathe as fast as when you're awake, right? So you're essentially hypofantillating when you sleep. When you hypofantillate, it retains CO2. When you retains CO2, you get a respiratory acidosis. So that acidosis, right, can trigger more complement-mediated lysis of your red blood cells. So you observe more hemoglobinuria in the mornings, okay? So, so the presence urine just looks very red in the morning. So that's a potential mechanism behind the red urine that's observed in the setting of, uh, P&E. So you can use that hamstest to diagnose a P&E. We're really the method that's essentially used by every lab these days is, um, uh, like flow cytometry where you basically detect the absence of CD55 and a CD59. And one thing I'll go ahead and say that me show up more on step two than step one is that, um, P&H is actually not, uh, an acquired, it's not like a genetic disorder that's like transmitted from, uh, like this, that 12-springo, whatever, no. The way it usually happens, it's, it's almost always an acquired defect in that peak aging that ultimately causes, uh, the problems that observed, uh, with, uh, with P&H.

And obviously, right, as I described in the podcast this morning, you treat P&H with aculesumab. It's a monoclonal antibody against C5. Well, remember, prior to giving a person, um, aculesumab, you certainly want to vaccinate them against my cereals, right? Because by giving aculesumab, you're inducing your pharmacologically inducing a terminal complement, uh, complement, uh, deficiency, which in this case is, um, um, um, um, C5, right? Because you're essentially blocking, uh, C5, uh, by giving a aculesumab. And I mean, you, that's like, I mean, you're essentially taking that medication for the rest of your life, um, aculesumab costs a ton of money. It's like, last I checked, it was about 440,000 a year. But, um, if you're looking for more definitive treatment of P&H, you can actually do like a stem cell transplant, um, and that would essentially take care, uh, take care of the, take care of the issue. So, I think that's all I want to say about, um, P&H, I really want to finish this podcast in under 30 minutes. That's like literally my target. Um, let's see, is there any other disease I've really not talked about? Come on, divine think. Oh, sickle cell, sickle cell. Let's talk about sickle cell. I haven't really talked about sickle cell yet. It's a floridly high-yielded disease, uh, to know about for your USM list, the point example, right? So sickle cell disease, it's another zomor recessive disease. And basically, it's a mutation in your beta-globing gene chain, right?

So, you basically substitute a glutamic acid for a vein, okay? When you have that, uh, substitution of glutamic acid for a vein, then your red blood cells begin to assume sickle shapes. Now, when they assume those sickle shapes, they can begin to clog off blood vessels, and that can cause lots and lots and lots of problems, right? So, for example, one problem that can happen is, a person can have like, uh, like bactylitis. In fact, that's one of the most common presentations in kids, right? So, like, bactylitis where they have like viso-like viso-clusive episodes of like the blood vessels that feed your fingers, okay? So, like, painful bones, painful hands, painful fingers, and a young kid, that's sickle cell disease onto proven otherwise, okay? Bactylitis, that's one of the most common presentations, another relatively common presentation of P and H. I mean, sorry, of sickle cell disease is something called acute chest syndrome, right? I mean, in fact, that's probably one of the most common causes of death, um, in sickle cell patients that are adults, right? So, adult sickle cell patients, one of the most common causes of death is acute chest crisis, and that essentially arises when you begin to occlude, um, um, that happens when you begin to occlude like, uh, like your pulmonary, like arteries, right? So, you begin to have, usually they will show you like a chest x-ray, and you'll see like an ill-defined, like, infiltrate.

Basically, if you see chest pain, the patient or the history of sickle cell disease, that's your diagnosis of acute acute chest syndrome. And, um, remember that patients, right, that have sickle cell disease, especially kids, they are susceptible to sepsis with encapsulated organisms. In fact, the most common cause, this is very high to know for the USML Es, the most common cause of sepsis in kids with sickle cell disease is strepnumol, okay? That is why kids with sickle cell disease, basically from when they are born to like the age of like five or six, they tend to get penicillin, like every day profilistically, so that they don't get, um, pneumococcal sepsis. I mean, they say divine, why do they get pneumococcal sepsis? The mechanism behind that is, remember your spleen protects you against encapsulated bugs. So, the thing that happens is that if you, if you, um, have a sickle cell disease, you essentially occlude blood vessels that feed the spleen, right? Like your spleenic artery, and that can cause like an infart of the spleen. So, these people essentially have like an auto spleenectomy in a sense. And when they have that auto spleenectomy, they lose the ability to protect themselves against encapsulated organisms like strepnumol, H-floor, and mysyria. In fact, most patients with sickle cell disease auto-infect the spleen by the age of like three, four, five, okay?

So, those patients, patients with sickle cell disease very early in life, you absolutely positively want to vaccinate them against strepnumol, H-floor, and mysyria, meningitis, okay? Against those shin organisms because they can get very severe sepsis and die. In fact, very high up to notice, the most common cause of death in kids with sickle cell disease is infection, right? And I would suspect that it's very likely from strepnumol because strepnumol is the most common cause of sepsis in patients with a history of a sickle cell disease. So, most common cause of death in kids with sickle cell disease infection, most common cause of death in adults with sickle cell disease is that acute chest syndrome. That's a very high up thing you want to know, for example. And I mean, obviously the way you diagnose sickle cell disease as with pretty much every other hemoglobin apathy is something known as hemoglobin electrophoresis, right? So, remember that sickle cell disease is a nozomer recessive condition, right? So, if you have like one bad allele, right? Obviously, you have, if you do hemoglobin electrophoresis, you'll observe regular hemoglobin A, like 50 or 55 percent. Remember, regular hemoglobin A is like alpha 2 beta 2. And then you also observe like 40 percent hemoglobin S, where you have, come on, divine think, where you have the bad beta glo... like the bad hemoglobin, right? That has the bad beta globin, right?

That has that glutamacid substrate for for for for for veiling, okay? Versus a present. So, that sickle cell trait where you have like one bad allele, right? But if you have sickle cell disease, that's where you have like both bad alleles. And that basically, I mean, obviously you not observe any hemoglobin A on hemoglobin electrophoresis, you'll just see hemoglobin S, but you'll actually also see hemoglobin F, okay? You'll also see hemoglobin F. Remember, hemoglobin F is alpha 2 gamma 2. Does not depend on beta globin chains, okay? So it will increase proportionally in the setting of a sickle cell disease. In fact, that hemoglobin F sort of tells you why patients with sickle cell disease, they really, really, if ever, get problems in the first six months of life because you have very high amounts of hemoglobin F at birth. So it sort of protects you against, protects you against the many clinical findings that are observed in the setting of of a sickle cell disease, okay? Now, also that also, I guess to sort of make another integration also tells us about treatment, right? So like hydroxyurea is actually used in the treatment of sickle cell disease, why? Because it actually increases the synthesis of hemoglobin F by an unknown mechanism. No one really knows why that's the case. So what's the other thing I want to say about sickle cell disease? Again, I apologize for the arms and arms.

These are lectures given from, again, I have usually the way I set up these lectures because when you ask me, how do you come up with these lectures? I sort of decide on general topics I want to discuss and then I just sort of talk about them in a free flowing freestyle kind of format. Okay, so yeah, I think that's all I'll say about sickle cell disease. I mean, it's a little more recessive already mentioned that you have the glutamic acid to valina substitution that causes the issues. Remember, actually don't forget hemoglobin C disease, right? Hemoglobin C disease is where you have like the glutamic acid that's substituted for lysine, right? And you can have some people that can be like compound heterosigotes where they have they have like hemoglobin S and hemoglobin C. Okay, those are classic things you probably want to know for an example. In general, hemoglobin S C disease is not as bad as hemoglobin, like it's not as bad as a sickle cell disease, right? So it's like sickle cell disease, you have hemoglobin S S that's the worst. There is hemoglobin C disease, although this is like super super super super rare where you have like two bad copies of hemoglobin C where essentially you have the glutamic acid to lysine substitution on your two beta-globin genes, okay? And then you have hemoglobin S C disease where you essentially have hemoglobin S and hemoglobin C and then you can have like sickle cell treat where you have hemoglobin A and hemoglobin S.

So in order of which is the worst, right? So hemoglobin, I mean sickle cell disease is the worst, that's where you have S S. Hemoglobin C disease is the next worst, like it's like in order of decreasing severity, hemoglobin, I mean, why do I keep saying this? Sickle cell disease where you have S S followed by hemoglobin C disease where you have like your homozygous for like the bad hemoglobin C and then hemoglobin S C disease and then sickle cell treat, that's the order of badness from most bad to least bad, okay? In fact, for the most part, sickle cell treat is asymptomatic, contrast that with sickle cell disease that is definitely symptomatic, okay? And remember, again, most common cause of sepsis and patients with sickle cell disease think about strep pneumo and then if you also see like osteomyelitis and a patient with a history of sickle cell disease, you probably want to think about some onella, one that those are circumstances, okay? So that is all I think I am going to say with regards to sickle cell disease and personally, I think I have discussed everything I want to mention in the context of hemoglobin, hemoglobin, they are podcasts specifically for those just sort of look further on my website, I should be good to go. So I wish all the best, and again, as I round up, I do offer one on one treatering for the USMLE step one, two CK two CSN step three exams, after thousands of people for those exams and many of them have gone on to do well.

In fact, I've never had a person I treated, I failed the USMLE exams and most people that many, many people have treated have gotten in the high 240s, 250s, 260s, 270s on those exams. And then I also tutor for the like med school shelf exams and the preclinical exams, right? So like the exams you're taking your first two years of a med school. And then I've also been on the admissions committee of a top three med school, I have like one year experience with that. So I do actually prepare like era's applications for med students applying for residency and Amca's applications for college students applying for med school. And then on the off chance that you have a relative that's taking organic chemistry, I do also tutor organic chemistry. And then I also tutor for the internal medicine in training exam and the internal medicine board exam, believe it or not. So have a wonderful rest of your day, have a wonderful Sunday, I will see you in the next podcast and I will see you at a anniversary, that's actually the 14th of this month, that'll be a one year and an anniversary. So have a wonderful day, God bless, see you next time. Thank you.

Spectrin, Band 3, and Anchoring protein.

Schistocytes (fragmented red blood cells) and low haptoglobin levels.

Streptococcus pneumoniae. This is due to autosplenectomy leading to loss of protection against encapsulated organisms.

Direct Coombs Test (Anti-globulin).

Sickle Cell Disease ($\text{HbS}$).

Sickle Cell Disease ($\text{SS}$) > Hemoglobin C Disease ($\text{CC}$) > $\text{SC}$ Trait.

Osmotic Fragility Test and Acidified Glycerol Lysase Test (or Eosin-5 malemite screening test).

Direct detects antibodies bound to RB Cs (e.g., AIHA); Indirect detects potential antibodies in the serum (used for transfusion screening).

It increases the synthesis of Fetal Hemoglobin ($\text{HbF}$), which helps prevent sickling and vaso-occlusion.

Thrombotic episodes, hemolytic anemia, and red urine/hemoglobinuria.

CD55 and CD59 (due to GPI anchor deficiency).

Acute Chest Syndrome (ACS), which results from pulmonary vaso-occlusion.

Osmotic Fragility Test and Acidified Glycerol Lysase Test (or Eosin-5 malemite screening test).

Direct detects antibodies bound to RB Cs (e.g., AIHA); Indirect detects potential antibodies in the serum (used for transfusion screening).

It increases the synthesis of Fetal Hemoglobin ($\text{HbF}$), which helps prevent sickling and vaso-occlusion.

Thrombotic episodes, hemolytic anemia, and red urine/hemoglobinuria.

CD55 and CD59 (due to GPI anchor deficiency).

Acute Chest Syndrome (ACS), which results from pulmonary vaso-occlusion.