Thalassaemia – Introduction, Classification, Clinical Features, Diagnosis, Treatment & Complications

hello YouTube I'm dr. Rob you I work as a lecturer of pathology in a Medical College Hospital and I am making this video for my students hope someone finds this helpful now today's topic is thalassemia so let's get into it okay before I continue with the definition of thalassemia you have to know some basic concept remember one thing thalassemia when you study telling you you have to know that this is the disorder of hemoglobin that's number one and number two here we are having decrease production of globing chain okay and one thing you also have to make a note of there is another disease or another disorder of hemoglobin which is called hemoglobin apathy and so you have to be very careful you know you most of my students make some common mistakes you know in the exam when they are asked what is hawa Samiha and what is hemoglobin apathy always remember Tala Samia there we're having problem in the globin chain as such that there is decreased production of the globin chain and in case of hemoglobin apathy we are making abnormal globin chain okay so as I have written in the ball you can see fallacy Nia versus hemoglobinopathies thalassemia in short it means the globin portion of the hemoglobin chain is not forming properly there is decrease globin chain synthesis and in case of hemoglobin apathy at the end of the world you have fatty that means here we have some abnormality in the globin chain okay so now we have cleared the basic difference between thalassemia and hemoglobinopathies now let's go into the definition okay I don't get scared I know it's a long definition but we will go step by step so in your textbook you will see a very long definition of talisay Mia and I have also written that here as you can see talisay Mia okay the spelling both are correct this is us spelling this is UK spelling so definition of talisay mia thalassemia is a heterogeneous group of disorder what do you mean by this that means this is a group of disorder where we have different types and their mechanism is not completely same for example you are a heterogeneous group of future doctors you know some will become sergeant some will study medicine you know all a doctor that's not the same similarly here heterogeneous group of disorder then what is their basis of forming a group the second point in your definition thalassemia is a heterogeneous group of disorder characterized by genetically determined reduction in the rate of synthesis of normal this is very important normal moving chain okay so I am repeating again talisay Mia what do we mean by talisay Mia number 1 talisay Mia is a disorder of hemoglobin how can we define how say Mia this is a heterogeneous group of disorder characterized by genetically determined what genetically determined reduction in the rate of synthesis of normal globin chain okay now now that we have known the long definition of semia we have to know a thing or two about the structure of hemoglobin because as I have already mentioned this is the disease of hemoglobin okay so first question where does hemoglobin come from we know it's formed in that developing red blood cell you know and if you recall your biochemistry you will remember that you have red in the developing red blood cell that is not the mature RBC I am talking about the developing ones the ones in the bone marrow their hemoglobin was formed in different compartments inside the cell for example in the mitochondria of those developing blood cells what we had we had glycine mixed with succinylcholine and they from something called Delta and I know the malonic acid can you recall yes this was formed in the developing red blood cells mitochondria then that thing came out of the mitochondria went into the cytoplasm and in the cytoplasm of those developing cells there were a lot of enzymes and they further modified this substance and ultimately made something that we can call purple firing and then that thing again went back into the mitochondria and there that infused with us ferrous ions Fe 2 plus and made something that we call him this is the heme portion of the hemoglobin and why did the globin came from Ruben was made in the ribosomes of those developing red blood cell and then they were fused so the point I'm trying to make here is in order to understand semia you need to understand the structure and how hemoglobin was formed and hemoglobin was formed not in one place but several places inside the developing cells okay now I have already said polycythemia is a disorder where we are having reduced production of the normal blue bean chain now can you recall what type of globin chains we have in our hemoglobin okay this is very important on the basis of the type of globin chain we can name hemoglobins in different names for example if we are talking about um hemoglobin a that has two alpha-globulin chains and two beta-globulin chains oh this is hemoglobin a okay next if we are talking about any one that is another variety of hemoglobin that hemoglobin had two alpha and two Delta globin chains there is another hemoglobin that we can see in the fetal life that used to work in the hypership circulation that is in the globin F and that's in the hemoglobin if we had to alpha and to gamma chains in the globin portion okay so now remember all these chains are globin chain and these are normal globin chains okay and in case of talisay Mia we are having reduced production of one or more of these normal globin chains so now that we have talked about talisay mia definition and structure of hemoglobin and how we name him ago beans let's now go deeper okay so basically we have types of talisay mia in south polycythemia we have reduced production of the normal alpha globin chain so that will be called Alpha Tau Xenia okay and similarly if we have a reduced production of the beta globin chains that will be called what that will be called something a beta thalassemia okay okay so now let's go deeper and first we will talk about beta thalassemia so digitalis amia means we are having decreased production of the beta globin chain but the thing is in the definition we have said a term that was genetically determined so what is the role of genetics in beta thalassemia remember one thing thalassemia are autosomal recessive disorder okay so the gene the gene responsible for making the beta globin chain is located in an autosome you know we have two types of chromosome in our body sex chromosome and autism and suppose I'm drawing an photos on here this is a chromosome you can see and these Auto Zone which is autism or chromosome number 11 this chromosome contains that genes to make the beta globin chain and as you can recall we have two chromosome 11 in a diploid cell one came from the father and one came from the mother and the thing that remember is each chromosome has one allele for the gene of beta globin that means in the chromosome number eleven that came from the father we have one gene that can encode beta globin and in case of the chromosome number eleven that came from the mother we also have one allele that contains that gene that can encode the beta globin chain one thing you have to remember about beta thalassemia also is that beta thalassemia occurs due to mutation of the gene so beta thalassemia occurring due to gene mutation and later when we will talk about alpha-thalassemia we will see that alpha-thalassemia occurs due to gene deletion okay so this is an important thing so let's now go to the mechanism I have already told you that the gene responsible for making that beta globin chain is located inside chromosome number 11 now what type of mutation can occur in that gene basically the mutation that can occur is variable so we will broadly classify this mutation in two extreme ways one type of mutation is cos beta plus mutation okay what is that beta plus mutation means here we we have mutation in the beta gene and so we cannot produce sufficient amount of beta globin chain however there is little bit of beta globin chain production that means in beta plus mutation we are having at least some beta chain produced okay and there another type of mutation in the beta gene which is known as beetle zero mutation this means if someone has this gene this gene is completely uncapable of making any beta chain okay and suppose I already told you that we weren't having one gene from the mother one gene from the father so this is the normal genotype both healthy beta genes some may have something like this one gene is healthy and one is beta plus some may have beta plus beta plus both genes are mutated and in extreme case there may be b20 beetle zero not only both beta genes are mutated but they are producing absolutely no bit above in chain okay so like I said as the genetical mutation of beta thalassemia is variable so we mainly talk about the two extremes of beta thalassemia so in one extreme we have beta thalassemia minor this is the general type of data Samia minor you can see we have one healthy gene and one defective or mutated gene so these patients are usually a symptomatic or they may have mild anemia and there is also some increase in the RBC count now the most important type for your exam is beta thalassemia major beta thalassemia major okay this is also known as Cooley's anemia and you have to know about this so what is happening here the genotype for batalla semia major is either this that means the patient has two defective genes of leptin encode beta globin chain and here absolutely no beta globin chains are produced or the patient can have something like this and that can also result in Wichita the simian major now what is happening here beta chain is completely absent so what will happen if you can recall the hemoglobins i had mentioned before hemoglobin a had alpha 2 beta 2 globin chains a 1 alpha 2 Delta 2 and movement F hat alpha to gamma 2 so in case of beta thalassemia major we are not producing any bit a chain so we will have decrease amount of hemoglobin a and since the other hemoglobins they don't need beta so their amount may increase okay but one thing that will happen still will have a lot of alphas you know that cannot find beta to make the globin protein so what will they do simple they will bind to alpha 2 themselves and that will form something that we can call tetra mark alpha 4 tetramer and when we have these things in our red blood cell that is not good what will happen the RBC's that contain these alpha tetra Mars today will get destroyed inside the bone marrow and that is called in effective electrophile is now even if those alpha for our tetramer containing RBC's if they are not destroyed in the bone marrow they will go to the circulation and in the reticulo-endothelial system that is the spleen the spleen will think something is wrong with these RBC's and spleen will destroy those RBC's so ultimately alpha 4 since we cannot make Vita so alpha 4 containing red blood cells will get destroyed okay and that will lead to anemia so what will happen next when our body sees that we are losing red blood cells rapidly it will try to produce more and more RBC's and how with our body do that okay so our body will do that by increasing the arm bone marrow by making our bone marrow hyperactive okay and that will lead to something interesting okay suppose if this is the bone in the center of the bone we have that bone marrow right in the center we have bone marrow okay so our body is trying to make more and more blood cells so it will expand this bone marrow okay so the bone marrow will get expanded and the context this one was the causes see this is the cortex and this one was the bone marrow cavity so as the bone marrow is expanding that will lead to thinning of the cortex and as we know our cortex gave the strength to the bone so when the cortex is getting thinner our bones will become weaker and that may also lead to pathological fracture so that's an important finding that we can in telomere patience moreover what will happen our body will see that we are losing red blood cells rapidly so it will try to make blood cells using all the bone marrow normally after birth only few bones make our blood cells you know those are the central bone marrows for example the bones of the skull the bones of the ribs vertebra and some few long bones they make the blood cells but here when you have so much loss of RBC's our body will try to make blood cells from all our bone marrow ok and what will happen as a result for example in our skull if this is the upper part of the skull and here we had marrow cavity so the marrow cavity is rapidly expanding to make more and more blood cells okay so that thing will expand and the matter will expand so rapidly that it will crack crack the scows marrow and it will look something like this and this is known as hair on end appearance or crew cut appearance of the skull bone as the skull bone marrow is rapidly expanding its expanding so rapidly that there will be some cracks in the marrow and that is called hair on in appearance also similarly as our bones of the face the bone marrows are expanding so our face face may give the appearance of chipmunk that's also lutein in some of your books chipmunk appearance on that face that's also another finding you can have in semia patient okay and one thing you have to remember that if the licinia patient gets infection viral infection by parvovirus b19 that is very dangerous in normal healthy persons if we get infected by parvovirus b19 our hemopoiesis get stopped for one or two weeks but since we have a lot of bone lot of blood cells in reserve so that usually is asymptomatic but in case of a patient who is having talisay Nia because I'll send me a major he is losing blood cells so rapidly that he needs all the blood cells made in the bone marrow so if we if we think that he is infected by a virus that stops the bone marrow from making blood cells that will be very dangerous for that patient okay so now that we have talked about the common clinical features of thalassemia what were they like instead they they were anemia and there will be some manifestations of increase hemopoiesis for example in the skull in the face and also when the body tries to compensate the loss of red blood cell destruction by making more and more blood cells from the bone marrow later it will decide that I have to make more blood cells outside the bone marrow and that is called extramedullary hematopoiesis and that will occur in the liver and spleen the liver and spleen will also get involved in making more and more blood cells which they actually did in the fetal life but not in the adult life but in case of thalassemia patient liver and spleen will also try to make blood cells to compensate and that will be to hepatosplenomegaly okay so there is an important finding and since they are not very good at making sells liver and spleen so they will make a lot of time immature blood cells that we can see in the circulation so in your textbook you'll also see something called nucleated our red blood cells those are coming from these extramedullary hematopoiesis so keep that in mind external or internal places that can lead to immature red blood cell containing nucleus now one more thing that you will see here is the target cell so when we will do lab diagnosis at our segmentation we will see those common findings anemia the anemia will be microcytic hypochromic anemia I'm just telling you the main things skipping the ones that you don't need okay so those things you will need for our written but for a Viper the examiners always ask you the main points okay so remember in case of the black picture of talisay Mia you'll have anemia in the blood field we will see those cells will be microcytic hypochromic and number one important thing for blood fimA thalassaemia is target cell now what is target cell so let's draw an RBC first okay so this is an RV C and here you know that the RBC is a biconcave circular disk 2/3 of it is red and the central 130s pale that is known as the central pelo okay because the central part does not contain any hemoglobin or contains less amount of hemoglobin so this is RBC viewed from the top and if we view the same RBC from the side it will look something ok I'm drunk this again it will look something like this you see biconcave we have one concavity here one concavity here and also to third is red and one-third is pale so what is target cell in thalassemia we cannot make sufficient globin chain so as we cannot make sufficient globin chain we cannot make sufficient hemoglobin so the amount of hemoglobin inside the red blood cell is decreasing okay and when the amount of hemoglobin in the RBC's are decreased you know RBC was filled with hemoglobin so when you were decreasing the amount of hemoglobin the RBC loses its tensile shape and then you can see some blebs forming in the RBC you know and those bless for example here will be a blood formation and drag this thing a bit larger so you can see suppose this was a normal RBC viewed from the side this is a side view and when we are having tala semia we're losing him a globe in so the RBC is no longer having its tensile shape so it will have some Blair's formed in the middle and hemoglobin will also begin to accumulate here in the center as well so this is a target cell viewed from a side and if we do the same thing from the top we will see some red area in the centre of the central paler just like a bull's-eye and from here we we got the term target cell so member travursel is a characteristic finding of thalassemia okay now so what will be the treatment of beta thalassemia the treatment of digitalis amia is blood transfusion okay usually the patient has to be transfused transfused blood regularly after four weeks interval and the problem is they you know blood contains iron blood blood bag contains iron remember one better blood contains 250 milligram iron okay so we are giving this patient this child repeated blood transfusion and that is correcting his anemia his problem of talisay mia but at the same time we are having a lot of Ireland deposited inside his body and always remember that iron has no specific or no well developed way of expression in our body we have ways to excrete a lot of metabolic waste product for example in the form of urea and other things but iron we have no mechanism to excrete iron that's why iron is very tightly regulated iron absorption but when you are giving someone blood you are bypassing those absorption methods and you are giving iron you're giving iron in the blood directly that means I am giving the patient blood and the blood contains RBC RBC contain hemoglobin and after 120 days after 120 days those RBC's go to the reticulo-endothelial system and in the reticulo-endothelial system they get destroyed once the RBC's are destroyed they release a hemoglobin then the hemoglobin gets broken into him and globin the globin portion goes to the protein Po and the him further breaks down into iron and other substance you know and that iron begins to deposit inside the patient's body and that is called hemosiderin seize and actually that is called hemochromatosis and that can be a problem and what happens when iron is deposited in different types of tissue they give different types of problem okay now that's the main thing about Vitalis amia and what can you say about alpha-thalassemia for alpha-thalassemia we again have to draw chromosome because remember in the definition I had told you that thalassemia was a heterogeneous group of disorder characterized by genetically determined reduction in the rate of synthesis of one or more will be chained okay now remember there is four gene or four allele for alpha chains of the hemoglobin so we have two allele in the chromosome number 16 of the father and we have two alleles in the chromosome number 16 of the mother why so many places that containing gene for alpha chain synthesis the reason is very simple can you recall he will be a a1 F all had alpha in their structure C hemoglobin a alpha 2 beta 2 a 1 alpha 2 Delta 2 hemoglobin F alpha to gamma 2 so you can see all have alpha in their structure that's why we have so many location in chromosomes for alpha gene okay now recall I have said while ago Vita Talalay Mia was due to gene mutation and alpha-thalassemia is due to gene deletion okay so what will happen if we delete one gene well basically nothing because you can see we still have three perfectly functional genes you know one here and two more here so one gene deletion that's usually asymptomatic so we don't need to worry about that okay next we have to ask ourselves what will happen if two genes are deleted okay so for example you see I have deleted two genes okay now if the two genes are deleted in the same chromosome this is called sis deletion and if the two genes are deleted in death different promotion for example one here and one here that is called France deletion and always remember since deletion is the worst one because if someone has chromosome like this okay and for example someone has another chromosome that also had a defective a deleted alpha gene then what will happen their offspring will have no alpha gene you know and that can lead to severe alpha-thalassemia so one gene deletion asymptomatic two gene deletion that can be abscess or trans variety sis varieties the worst one if we are having three gene deletion that is a very severe disease what will happen will very reduced production of the Alpha containing hemoglobins okay and what will happen we will have something that is called hemoglobin H okay so what is hemoglobin H hemoglobin H that means we have beta 2 and we have beta 2 that is bitter for okay this is hemoglobin H now if we have four gene deleted the all four alpha genes are deleted then what will happen then you have something called bar similarly that is gamma 4 you know gamma 2 combining with gamma 2 making gamma 4 and this type of hemoglobin is very non-functional so these babies will die a few hours after birth usually are they they are born dead no still but okay so that's also called hydrops fetalis okay so this is in short about the palace Amyas we have talked about the definition of thalassemia we have said that Palestinians are disorders of hemoglobin here we were having reduced production of the globin chains of the hemoglobin and remember this globin chains normal but their amount has been reduced there are two types of thalassemia alpha-thalassemia butyl Samia and we have discussed their mechanism and their treatment so this is in short about our semi


  1. No bullshit. Only core material. Some help with videography could be good, though. Highly recommended for any med student.

  2. Sir at 7:59 is that not have mentioned as HbA1..pls crct me if i am wrong sir!
    And what do u mean by increase in rbc count in 14:38??

  3. It is very unfortunate that some kids are born with bad blood. With 10,000 cases added every year, India is emerging as the thalassaemia capital of the world. Dr JS Arora, a thalasssaemialogist and general secretary, National Thalassemia Welfare Society of India has written an article on causes, symptoms, treatment and prevention of thalassemia. This informative article can be read on a popular Indian newsportal at following url:

  4. Mr Rabiul Hague your lectures are very good very nicely narrative and clearly understanding. Many medic are benefited and I am one of them from UK. Thanks a lot…
    I would like to suggest that if can do transfusion lectures and also on leukaemias as well.

  5. Brother this is the best lecture available in the internet on thalassamia..
    You are too good.

    Thank you.

  6. Thank you for video. Very nice lecture
    Sir I want more lectures on GIT specially in colorectal cancer and intestinal disease

  7. Thank you vary much doctor.. iam very understand your lecture..iam medicine student from iraq

  8. sir you told thalessemia is autosomal recessive but i found autosomal codominant in robbins book basic..what is right???

  9. Thankyou so much sir.. it helped me a lot. It is given much complicated in my pathology textbook. Thankyou again.

Leave a Reply

(*) Required, Your email will not be published