Chapters Transcript Video Thalassemia in Primary Care Thank you very much. We really appreciate the opportunity to present um today on uh thalassemia. Yeah, see here I get the right. OK, looks good, great. So, um we, we, we're gonna be talking about thalassemia um with the two things that um are going to the have affected how the the talk is modeled. The first is the the the setting in which Palestinians en encountered. So this is, you mean the primary care and, and not um in the hematologist office or not in as a part of a comprehensive um center. And the second is uh our location um in, in California and the population that we see. And the, the fact that you're living in a um under a, a state newborn screening program, which is the premier um program for thalassemia um newborn screening diagnosis, you know, throughout the country and pretty much has led the field um worldwide from the beginning. So, keeping those things in mind. Um the um just a quick note on my disclosures uh uh for doing clinical research trials on SIA related um new therapeutics and these are not relevant for today's talk. So I'm going to run through um say a brief introduction to thalassemia and why we call them thalassemia syndromes and just thalassemia. Um genotype and phenotype newborn screening as it applies to California and then thalassemia treat and most of all forms of thalassemia. So uh to begin with uh and um as an introduction to what thalassemia really is, um we, I want to point to the red blood cell. Um about 95% of the red cell contents are in the form of hemoglobin. And the hemoglobin is a, each molecule of hemoglobin is in turn composed of four global chains. Uh two of each two of one kind or two of another kind. So almost always the two chains are going to be alpha chains and the other uh two chains can either be two beta chains, two gamma chains or two delta chains. And that gives rise to the um the types of hemoglobin that we see beta two leads to a gamma two is fetal hemoglobin and delta two is the delta minor hemoglobin. If we look further into the hemoglobin, then there is there are three components to the hemoglobin molecule. One is the protein part that's folded up here. So that's the globin protein and within that is a coordinated the hem and the hem itself consists of a friend and at the center of which is the iron uh molecule where the oxygen is about. So, um that's the, the reason why iron deficiency and um gives rise to petros similar with thalassemia. But in thalassemia, it is the defect in making the protein part of hemoglobin. That's the problem. So it's a quantitative defect in globin synthesis and that leads to imbalance between the alpha chains and the beta or the other forms of chains. So, the genes themselves are located um on two different chromosomes. One, the alpha genes are located what we call the alpha locus. And that's on chromosome 16 and there are two of alpha chains. So that's the normal is they are duplicated chains and they make alpha uh carbon protein. And on chromosome 11 are, it is a beta locus which has better like chains including beta um delta and and gamma, which are again duplicated and the combinations. Um One from here and one from here give rise to many different um developmentally mandated hemoglobin species. Uh Our main um focus is on fetal hemoglobin which is gamma with alpha and then the adult forms, which is the, the, the beta in the delta. Now, uh the also a quick word on nomenclature. Um when we talk about hemoglobinopathy, distinguish between um things and mutations that cause a change in the protein structure. So these are structural hemoglobin and they often we just call them variants. And of course, the most familiar variant to us is the uh the Sickling variant. So, so hemoglobin s primarily and, but there are other variants that uh have other um um problems due to the protein structure being abnormal. On the other hand, uh when the protein structure is not affected, but the problem is that you can't make enough protein. That is the thalassemia and the thalassemia is are um of many different types. Um Again, either could be uh simply that the something is not working, uh completely, not working, that's a zero mutation. But if it's partly working, then it's a plus mutation and there can be various combinations um because there are multiple genes that are involved. So, um from the clinical perspective, thalassemia are the form of anemia and these are inherited anemia due to mutations and cobin genes, either alpha or beta that reduced the synthesis of globin chain. Uh the globin protein. Now, within um thalassemia, we often talk about either the phenotype or the genotype. When we talk about phenotype, we we can talk about phenotype independent of the what the underlying mutations are. For example, with thalassemia trait, we know it's a mild anemia and it's asymptomatic. We can talk about thalassemia intermedia, uh which we know that anemia can be quite variable but uh patients either not on transfusions or sorry, not requiring regular transfusions. And then we know what thalassemia major uh is the implication here is that there is very severe anemia and the transfusion are needed very early in life um for survival. So, um on the other hand, one can look at just the genes um and then talk about what are the underlying genetic defects that are producing thalassemia. So here the mutations can be either in the alpha locus or the alpha globin genes. So, these are the alpha thalassemia or in the beta genes. So these are the beta thalassemia and it isn't always possible to infer the phenotype if we are only given the, the mutations. So clearly we need both the genetic test as well as the, the pheno. Mm. So um just taking that a step further, um we have two copies of alpha genes and one copy of beta gene. So um in, in some sense, um discussing beta thalassemia are simple is a simpler thing to do because we uh this is chromosome 11. So there's a maternal chromosome and a paternal uh chromosome and both have one copy of beta gene each and if one of them is nonfunctional, that give rise to be pam treat for alpha thalassemia, now we have duplicated. So there's a total of four alpha genes. Um and you can have a silencing of one gene, two genes or or more. But uh for when we're talking about trade, we are usually implying that the two of the four genes are inactive, but the two inactive genes can either be on the same chromosome or they can be on the opposite chromosome. Uh you know, also known as cyst and trans deletions. Um and the hematological implication in terms of what the hemoglobin level is gonna be and how the patients can behave. Clin Yeah, exactly. There, there's hardly any difference between the two. But what is very different is the implication for de genetic counseling. Um And obviously the, if, if, if, if this chromosome is passed on to the child, there is a potential for severe disease depending on what the partner has and that risk is uh not there uh with um, if, if you have trans lesions. So the the phenotype that we see in in, in uh hematology practice is quite variable. And uh we often tend to more often see the most severe cases. But the phenotype um or thalassemia can be presented along a continuum. Uh whether patients either have no transfusions may require an occasional transfusion, but they need to be started on transitions because anemia is too severe or they will, they cannot live uh unless we regularly transfuse them. And from uh there are two different classification systems that have been used. Uh On the top here is patients who are classified either as non transfusion dependent or transfusion dependent. So this this this is a descriptive term based on whether or not we feel that the patient needs to be started on transfusions. And in the old older sense, uh you know, we, we know what tele major means which means transfusions for survival. Whereas intermedia occupies this large space in the middle where you may need no transfusions, you or you may need occasional transfusions or even more than that. So, there is this um region of this spectrum and patients are have never been transfused but have more than trait. And this is uh the kind of patient who is likely to sometimes not be diagnosed uh or sometimes is present late in life or uh initially suspected to have thalassemia more than trait in, in the primary care setting. And one can do the same exercise for alpha thalassemia. And here, all we're doing is replacing reed um genotypes with hemoglobin, H for alpha thalassemia. And again, there is this uh group of patients um who um are not, who have never been transfused and may not have come to uh have had a hematology evaluation but may 1st require a diagnosis in, in the setting of their um well, child care or, or when they're acutely sick. Now, for um the uh discussion of thalassemia really is incomplete without understanding the ethnicity distribution of the mutations. Um And uh this uh study um done what 15 years ago or more um look at the worldwide distribution of severe thalassemia, uh birds with severe forms of thalassemia. So, both for beta thalassemia and in red is the alpha thalassemia and the um the regions are dis distributed according to um the World Health Organization uh representation. Uh And, and as you can see um from nearly 60,000 birds per year of severe thalassemia. Um this, this uh column is just sliced up to see where most of the uh births are occurring. So, in, in the American region, for example, there's a very small um part of this uh column. Um The same applies to Europe European region. And in the African region, especially sub-saharan Africa, it's really sickle cell is that it's a dominant hemoglobin uh disorder. Um But then in North Africa and Eastern Mediterranean, um thalassemia birds are very common. Um And these are um as I'll mention later, we are new patients that we've seen. Uh we've seen them from, from this region. And then um perhaps the largest number of me thalassemia patients are coming from South and parts of Southeastern Asia. Um and then um is the Western Pacific that includes uh China and Philippines where alpha thalassemia is probably even a larger proportion of the total severe cases. So that has influenced um the type of patients uh the ethnicity of the patients that we see here. Um because um for us, thalassemia is predominantly a disease um that um it, it affects our, our immigrant populations. Um I think that they, they almost um we had patients who speak over 20 different languages and providing them with culturally appropriate care is a very big part of uh what we do. Um And understanding the limitations sometimes that come with the first generation immigrants and as well as um increasingly, we're seeing refugee um um families from conflict zones Um So, so these are um you know, a part of um us being able to provide comprehensive care. So, um I'm going to spend a few minutes talking about the California Newborn Screening program that has uh affected a lot how uh thalassemia is diagnosed. And also it's I think equally important for us to understand what is not covered in, in the newborn screening program. So um the the spinning for hemoglobin disorders um started in, in uh 1990. Um but like unlike many other states, um California opted to uh use um HPLC chromatography uh instead of using electro Rees or to electro focusing or other methods. And the big um um advantage of this was that you could um to um break down the hemoglobin species and do a very good quantitative estimation of the relative proportion of hemoglobins now. But the as as we know, the the screening was started initially for sickle cell disease. And for uh you're familiar with the they, yeah, the screening uh panel, the the rus for the recommended uniform screening panel, you know that the sickle cell disease is the condition that is the primary screening condition. And um thalassemia are not mandated or not part of that list. But um because these are secondary conditions that will show up when uh HPLC is done. So, um California has has adopted a work um method where patients with lye can be diagnosed and um managed early as well. So, um in, in that category, we have uh all forms of alalia that um are included. Um all beta globin variants uh can be picked up. Um And for beta thalassemia, uh beta thalassemia major can be picked up and beta thalassemia with variants can be picked up and some other disorders as well. Um How common is uh a bird with the Thalia syndrome in, in California? So, here's a comparison of the prevalence, birth prevalence per 100,000 birds. Uh From uh this is data from the California Department of Public Health from the newborn screening program showing that be to sickle cell thalassemia is less common but it's, it's not rare. Um um And and there is a lot more thalassemia that is picked up at birth compared to be. But the prevalence is um maybe two thirds of the of the prevalence of sickle cell disease. So you thalassemia is a common condition picked up at birth in California. Um uh Here I just want to briefly present and maybe would serve as a resource slide more than a discussion today. But um the the diagnosis that is made on the or, or, or I mean on HPLC on newborn screen is a pattern of hemoglobin. So which is represented by a sequence of letters that represent the hemoglobins from the least uh from most to least abundant. For example, a normal newborn has about 70 to 80% fetal hemoglobin. And the rest is hemoglobin A. So the pattern fa uh would then be a normal pattern. Um And that's a normal diagnosis. But if, if only F is seen and A is completely absent, that uh would imply that there is no beta gene output. So this is a beta thalassemia major. And, and then the, the other category is where we have a variant. And in most cases, the variant, if it is identified, it would just be written as a sickle variant or E or D and others. But if it's a rare variant, then it will just show up as a V. Um And, and then uh there is a distinction between whether the variant is more um pro the proportional variant is more than the proportion of uh hemoglobin A or on the other hand, if the proportion of hemoglobin A is more than that of the variant and both have different implications. Um um This, the heterozygote variant should be less than, the proportion of variant is less than the proportion of a uh hemoglobin age is diagnosed by the presence of bars, which is more than 25%. And finally, there's a category of transfused newborns where the, even though I think the guidance is to take uh to obtain the sample um prior to transfusion, but sometimes that is not manageable. And in those cases, um uh e either uh it, it should be indicated on the sample that this is a post transfusion sample. And sometimes it can be um estimated from the pattern of the hemoglobin. Um and, and if, if, if it is felt that the, the child has one of the significant disorders, um like sickle cell disease or the thalassemia major or um some form of uh uh thalassemia, then a second blood sample is obtained and this time it's a been a sample. Um and that sample is sent um to our hospital in the Oakland campus here to the hemoglobinopathy Reference laboratory to do further work up and to confirm with genetic testing that the the diagnosis indeed is what is correct, what, what was originally suspected. So, so that's all well and good. And I I think the, it's, it really is a, a brilliant method for uh detecting most of the cases with thalassemia at birth. But there remain some um forms of thalassemia that are not detected by newborn screening. Um And just for comparison. So if you, if one looks at sickle trait that is diagnosed diagnosable at birth, e trait is diagnosable at birth. But if it's a beta thalassemia trait, um there is, it, it, it cannot be picked up on, on the HPLC pattern. Same thing goes for alpha calcemia trait, um either one or two gentle um because the Barch level to increase is less than 25%. So, so that is also been diagnosed, but these are traits, uh what's more um relevant is the fact that beta Thales intermedia uh cannot be usually be diagnosed at birth because the mutations that underlie uh in intermedia and mild mutations and they still make some hemoglobin a. So the pattern remains fa and that cannot be distinguished from normal. And this can even happen with certain types of major if one of the mutations is mild and one is severe. So, um so having a, an a pattern doesn't completely rule out um thin better thalassemia at birth if both parents are carriers, and then there is a group of individuals who are not born in California. So they see their birth in another state uh that have different standards of newborn screening or they're immigrants from another country. So the fact that we, we're likely to see trade, um we and if we see trade, then there is the need to distinguish it from iron deficiency. There are conditions that are not detected by newborn screening and then the Children not born in California. Um These are the various groups that 1 may encounter um in primary care practice. Um So a special mention um I think should be made for hemoglobin. E um and that's because e is a very, very common uh variant um for um especially for California, I I, I'd say throughout the west coast. Um and also increasingly for many other um the regions in the country depending upon the pattern of migration. So um e can just be a as a trait um he will go with A E uh the thing to note is that this isn't like a thalassemia trait. So the, it's a hematologically silent. The CBC changes a very minor and usually not enough to want to suspect that the child may have hemoglobin uh E trait when those who have homos e um will not make any hemoglobin A but the hematology is just like be athalia trait, which um is when we talk about this later, is hemoglobin about 2 g below the normal range uh for age as well as microcytosis and hypochromia. And these patients need to be distinguished from um iron deficiency. Um and they require genetic counseling because they're carrying e uh two copies of e the third category is the E when is inherited with the beta thalassemia mutation. So, this is beta thalassemia and that's a serious condition. And these patients require um they're complex and require specialty care from the very beginning. And then we can have e inherited with various types of alcohol, either one or two or three gentil les. Um and, and they, they usually not a significant contributor to the pheno type. Now, in um the initial years of testing, um the, the, the California Department of Public Health published um their um estimates of how many um birds happen that have a hemoglobin. E so e trade. Um and then they um because they had data on ethnicity, they could break it down uh and among um the, the Asian ethnicities that they uh they did, they don't include all. But that's the data that they had at that time. Uh It could be seen that the Southeast Asian um um um ethnicities, especially Cambodian and Lao and Thai. Um and, and the others had a very high. So for Cambodian, for example, this district is almost one in five Lao and Thai, one in 10 Vietnamese, one in 50 same with the and less. So Chinese. So if, if, if uh e is that common, then um one can imagine that birds with homozygous e uh or the fe pattern will also be fairly common. And the they were estimated to be about 60 birds per year uh with the um the fe pattern. But the, the, the fortunate thing is that most of these patients tend to have uh hemoglobin, homozygous ee and, and very few have the E but is zero thalassemia. So, um well, even though E is very common, uh and there seems to be, he thinks the incidence of eberly is relatively rare. So that uh brings us to um the first case for discussion here, um a nutritional anemia or something else. So this is a um yeah, a six year old girl who come in for a routine health visit. Um She says symptomatic growth is slightly delayed, appears pale. No, the physical findings and a hemoglobin check in the clinic shows 8 g with ci the family, they're refugees from Myanmar and they've just arrived in the US. The lamps are obtained um because of the anemia, um hemoglobin is 8.2 M CV is 65. So hyperchromia microcytosis. RDW is high. Uh RB CS are reduced and then they are nuclear red blood cells observed in the in the um differential white and white cell and platelets are normal iron saturation is 45% better than the 60 nanograms per meal. And the question is uh what is the, the next step? So the choices that we have here are that we could start a trial of online. And I would say that uh of course, it's not indicated based on the fact that the fins are saturation are both normal but also um and and this may just be a personal perspective that uh giving over line based on uh um point of care hemoglobin alone is OK. If the hemoglobin is, is not too low, but if it's less than nine, then it's probably best to check a CBC and a first. So we wouldn't choose that option. The second option is uh just knowing the, the ethnicity and the fact that the baby, the child wasn't born in California, we could draw further labs. Uh we could check and reticular accounts that would support whether there's a hemolytic anemia. Uh we could do electro freezes and in this case, it showed 45% hemoglobin E 50% hemoglobin F and there was an absence of hemoglobin A and then beta globin gene testing was considered as the next step. Or um there could be a, the second um step could be skipped and a just a referral to hematology but also be considered. And I, I think both option two and option three would be equally correct in my view. And in this case, the, the diagnosis is hemoglobin e thalassemia. Uh that's a serious um form of thalassemia and it, it, the child requires um hematology, um follow up and care. Ok. So, um uh moving on to a discussion uh about thalassemia trait. So thalassemia trait is uh a generic term and we, we are either referring to beta thalassemia trait or alpha thalassemia trait. And um this is a mutation in one beta gene, the beta a being the normal beta gene and the the other is either a beta zero mutation or a beta plus mutation or it's an alpha thal asymmetric where there are two of the alpha genes are deleted either in cysts or in trans here. Now, what are the characteristics that qualify the hematology picture if you didn't have, if one did not have the genetic testing available, what would be compatible with thalassemia trait? So first, just looking at the hemoglobin level is about 2 g lower than the mean for age, not three or four or 5 g, but um about 2 g, both the M CV and the MC H are significantly reduced while the red cell count is increased and the RDW is either normal or increased. The usual. The second thing is the usual hemoglobin level just building on the 2 g below. The normal age is the for a child, 9.5 to 11 for um older girls and then boys um about two grands below what's expected to be there. Um And, and then finally, the fact that there is no significant increase in particular sites or bilirubin. So, no hemolysis can be detected. 39 iron saturation are uh either normal or low but not increased, which happens in the more severe forms of thalassemia. Um There is the absence of splenomegaly and there are no bony changes from matter expansion. So if, if those um uh things uh those considerations are met, then one can be reasonably confident that telemetry is present um in, in, in general. Um So um it at least from hematology perspective and that may not be the practice guidelines. We do recommend uh checking iron uh more frequently. Um um for cases who have microcytic hypochromia anemia. So if, if a child presents with uh anemia that is qualifies to have low M CV, low MC H and taking a fin as a first step. And if the fin is low than to do a over iron uh supplementation and repeating up two or three months, if there is no improvement or if the fin was normal to begin with, uh then the hemoglobin elect freezes is done. And if the, if it shows that the hemoglobin A two is elevated, then it's better thalassemia. Um one should do genetic testing for that. And if it is normal, uh then the genetic testing. So alpha thalassemia does not have any signature on hemoglobin electrophoresis. So genetic testing is the, is the correct um form of confirmation. But this again uh is applicable only if the anemia um is, is not more severe um than two or 3 g below the normal range. So case number two is the question of whether this is this more than trade. So this is a boy who is now um 20 years old. So when he was three months old, uh he was seen by his pediatrician, had microcytic anemia at three months. Hemoglobin was 9.5 M CV was 73. Um Sorry. And both parents had verily known to have better thalassemia trait. It was suspected that the infant also had better thalassemia trait. But of course, with both parents being carriers, he at with the major. So he was followed closely. And then by the time he was 12 months old, it was felt that he diagnosed a bit of thalassemia trade is a likely diagnosis. Uh anemia is mild, stable uh CBC, but this is consistent with thalassemia trait. And in fact, a a hemoglobin electro was sent that I'll show you in a minute when, uh now he was a 16 year old teenager who was admitted uh urgently because uh he was transferred from an outside facility of the sustaining blunt abdominal trauma. He fall into a handlebar of his bicycle and had a great for spann laceration. And when uh surgery, uh when CT scan was done in, they actually had a splenomegaly and that led to a hematology consult. So, uh over here on the right side are the um uh different CV C and other values from one year and from 18 years. Um And if you in between the hemoglobin level, um has not been too low. Um just at the bottom line of what we were discussing, uh he has the other characteristics. Um And the, the if, if, if one were to retrospectively just think about this case. Um The fact that the fetal hemoglobin was 21% in one year. It is uh it's a lot more than what you would expect. Um because even by um this is high, even for a six month old baby. And by the time you're one year old, if you didn't have any form of thalassemia, he hemoglobin f would be less than 1%. But, but in any case, um there was a hematology consult and then a diagnostic test was done. Uh The beta gene actually was confirmed to have the one copy of a beta zero mutation. So that's compatible with beta curing and trade. But the analysis of the alpha globin genes showed that there was a triplicated alpha gene. So instead of four normal copies of algen, he had five copies of the ALPA gene and which exacerbates the anemia and and really makes it into a thalassemia intermedia instead of a thalassemia trait. So, the diagnosis is heterozygosis senior intermedia and that was the reason for his stomach enlargement. So, over the years, as uh we've all um learned, there have been many attempts at uh differentiating between uh thalassemia trait from iron deficiency anemia based on the CBC alone without resorting either to um iron, um measuring iron saturation Froin or genetic testing. And these are the indices that have been developed and the the best known in um is our own men index that was developed here at U CS F. Um And there have been others over time with different sensi sensitivities and specificities. Uh Some of the more recent ones that are using artificial intelligence uh to look at a number of different parameters uh tend to be do better. Um But the um the dementor index I think has the advantage of being of a simple um calculation um and that can be indicative of thalassemia trait being present. Um I just put this in here. Uh RDW is often, you know, part of it distinguishing between iron deficiency and uh thalassemia trait. Um It certainly is a, a sensitive test but its specificity uh is is very, very low. Um And in fact, if you want to choose between red cell count and red cell distribution width, and the red cell count seems to be um may even be slightly better um to, to take on. So the other big problem uh with uh using indices like these is that they all when they were created, uh the patients who had iron deficiency and thalassemia trait together were excluded, but that's not the real life. Um because many Children with trade also have iron deficiency. In fact, in, in this uh clinical study on the right side, uh patients who had three plus iron deficiency um with a ferritin of um seven before uh iron supplementation was given, it was corrected over a period of five or six months to um a normal ferritin level. They had an increase in their baseline hemoglobin from 9.8 to 10.8. And not only the hemoglobin increase, but many of the uh the N CV MC HC. Um uh and the and they, they all improved and the rates of distribution rate uh um improved as well. So that brings us to our uh next case of uh a normal newborn screen. So this is a child was born at 41 plus weeks of pregnancy that was uneventful. Her mom had been told that she had iron deficiency. So the first child, uh parent ethnicity is Chinese and Indonesian, the normal birth weight, there were no concerning perinatal events hit Mile jaundice uh in CBC on the first day of life at the hemoglobin of almost 21 with an N CV of 97. Um and the was never too high. Both parents were aware of being beta thalassemia carriers. And when the newborn screening result came back, it was normal child was well for the first two months. Um good weight gain, uh feeding well and then the weight can begin to slow down. Um The feed volumes went down. Um There were no overt respiratory symptoms or sweating. Uh He so during this time, there were many visits uh to uh the pediatrician's office. Uh several times seen for failure to thrive for thrush. Uh He was noted to be a quiet baby who slept well was meeting developmental milestones. There was a heart murmur that was evaluated by cardiology and deemed to be a flow murmur. And at six months, because of these concerns were persisting. A CBC was done and the hemoglobin uh was 5.3. Uh he was admitted the same day to a hospital. The pin was 4.8 and he was microcytic and tics and Billy Rubin and, and then a smear that uh showed um many changes and he was also noted to have enlarged liver and spleen. He was given as red cell transfusion and there was an immediate change noticed in his activity in appetite. So, um a electrophoresis was sent right before the first transfusion was given. And that showed that um at seven months of age, the, the child had 72% fetal hemoglobin and only a small amount of a relative to half. Um And this is indicative of a beta thalassemia syndrome. Uh And then a beta gene testing was done that showed a beta zero mutation with a beta plus mutation. There's a sequence of events. Uh The first hemoglobin of 4.8 the first transfusion was given here. Uh And then we waited and then when the hemoglobin fell again to below seven, the second transfusion was given. And once these, these two events happen, then that's a fulfill the requirement for a diagnosis of beta thalassemia major. And then the child was put on regular transfusions to maintain his pret transfusion hemoglobin always about 9 g per deciliter. So, um thalassemia trait um for um from our own data, uh is not limited to any um one ethnicity or the other. We we've seen um this is 45 consecutive patients with telemetry. We saw over a couple of years. Um So they are African American Asian, Caucasian Hispanic um and South Asian and the, the distribution of alpha versus beta changes. But um but telemetry um is should be suspected um based on hematology uh regardless of ethnicity. Um And we, we've always been concerned about the overlap of iron deficiency anemia with thalassemia trait. Um um and is this is because the ethnic groups and, and uh that are at risk for iron deficiency are also um affected by thalassemia trait. Um And the CV C results don't reliably distinguish between the two conditions. Children with trait can have iron deficiency anemia. And Children with iron deficiency anemia can have under length hyem traits. So both things can't happen together. Uh which is why we can favor um doing a hit at least a more frequently. Uh if, if one is in this um differential diagnosis situation. Um and um just by uh this is just one slide, nothing to do with thalassemia just to show that in the Bay area. And um we have um witnessed and i it's probably true for the um other parts of the country as well, a change in the risk ethnicities for severe and deficiency anemia. And that the majority of patients that we see are um are of Asian um ethnicity or, or Hispanic. Um And um unlike in the past, uh there are many less, much less African American Children being affected. So it brings us to the last case in the last couple of slides. Um an international traveler. This is the three year old child who's coming in for a well child visit. Uh She was born in uh China, uh then moved back to us for a short period of time. And then at two years while he was living in the US, he was uh seen um for a well child visit and there was um he had anemia. So as investigations were sent that identified him as hemoglobin aids disease, but then the family went back to China and then the return um to live in the US. And then in the meantime, he had not had any hematology follow. So at this visit was noticed that he had been a healthy child, Um noted occasionally to have uh maybe pale look, looks pale, sometimes one hospital admission for an unrelated event. Um The iron intake was noted to be poor. The point of care hemoglobin at this time was 8.7. Uh and it was uh at this time, it was realized that the child has had some previous investigations and that there was a hemoglobin electrophoresis from when he was two years old that was concerning and that needs confirmatory testing. So this is uh what it showed there was a, a anemia. Uh the retic count was slightly high. Um This Ron saturation was normal and then the electro freezes showed that he, he had um these abnormal hemoglobins with bars and hemoglobin H were still present. So, uh genetic confirmation of the diagnosis um showed that he has the, the two gene alpher dele along with the one alpha dell. So there's three out of the four alpha genes are deleted. So he had uh hemoglobin H disease. Fortunately, this type of hemoglobin H disease has a very benign clinical course. Uh transfusions are not needed in we expect normal growth and development and other than a fully supplementation in genetic counseling, uh these patients often don't need any other care. And with that, I want to thank um um um the Comprehensive Thalassemia Center, um the staff uh Doctor Wicinski, as well as the hemogram reference laboratory at Children's Oakland, um who have contributed so much to our knowledge of thalassemia. Thank you. Great. Thank you, Doctor Law. Um Let's see. Let's open it up to questions, see if anybody has any questions and then as a reminder, um once we finish, once we sign off here, your evaluation will populate in your browser. So please fill that out or you can fill it out in the email that comes tomorrow in your, in your inbox. Let's give it one more minute for questions. I don't see anything coming through quite yet. Let's see here. All right. Well, Doctor Law, thank you so much for taking the time out of your day today to present to us and thank you everybody for attending. 00, like something came through. Let's see here. One person says, thanks for the excellent presentation. The next question asked, you seem to use Frain for, for 20 for iron treatment and anemia. I see lots of kids with Froin of seven without anemia. Do you recommend treating them? Right? So, um when if the fin is low that is tells us what depleted iron in the body. And um so anemia is usually the next stage in, in iron deficiency. So, if for the first, um the first phase is the development of depletion of stores and then this, if that is not correct and then eventually the hemoglobin level will start to fall. Um So yes, we do recommend treating iron deficiency, irrespective of the hemoglobin. Just the dose of wine may have to be different depending on the circumstance. Great. Thank you. All right, we'll give everybody a couple minutes back on their lunch hour again. Thank you for attending. Please be sure to fill out your evaluation to get your sumi credit. If you have any questions, don't hesitate to reach out to your physician liaison again. Thank you, Doctor Long Doctor Law for your great presentation and we hope everybody has a great day. Thank you. Created by
