CBC | Approach to Anemia

what's up ninja nerds in this video today we're going to be talking about red blood cell disorders that includes anemia and polycythemia if you guys like this video if it makes sense and you enjoy it you know what to do hit that like button comment down in the comment section but most importantly subscribe also you want some amazing notes illustrations i highly suggest you check them out go down the description box below it'll take you to our website where you guys can follow along with me during this lecture now this is going to be a little bit different than our normal lectures where we go into tons of detail about pathophysiology and we go down this rabbit hole kind of sometimes in this video this is going to be a really like very systematic approach a step-by-step approach of whenever you order a cbc on a patient you see that they have signs of anemia or you say they have signs of polycythemia what are the next tests that i should order what would that test tell me and then what we'll do is we'll do some case studies to really make sense of all of this it's going to be quicker it's not going to be a ton of explaining about things i just want us to have a very systematic approach and then we'll do repetition afterwards okay so let's get right into it however in order for us to understand red blood cell disorders we have to have a little quick tidbit on the life cycle of the red blood cell if you want more detail we do have a video where we cover the whole life cycle and entire destruction pathway of the red blood cell in our physiology play let's go check it out in hematology but for this one we're going to keep it basic when we talk about red blood cell production it occurs where and the red bone marrow yep that's right you got it now in the red bone marrow we start off with a cell called a myeloid stem cell now the myeloid stem cell what happens is it can become a red blood cell it can become a platelet or it can become what's called a neutrophil an eosinophil or a basophil how does it know to go to become a red cell did you just be like all right i guess i'm going this way no it gets a particular stimulus what are those stimuli there's a lot of things to be honest with you what i want you to remember basically is it receives hormonal particular stimulus it receives a lot of nutrients that are very essential for making a red blood cell but you know what unfortunately we take drugs or prescribe drugs or there's certain toxins that we're exposed to that can actually inhibit red blood cell production so remember not only can we stimulate it we can also inhibit it unfortunately and just remember the bone marrow the actual cells inside of the bone marrow have their own intrinsic type of activity so here's what i want you to remember we need particular hormones to drive red blood cell production what are those hormones first thing thyroid you need thyroid hormone so t3 t4 if you have anemia okay you're not making enough red blood cells and there's a drop in hemoglobin dropping hematocrit maybe you have a low t3 t4 your kidneys your liver it actually makes a hormone called erythropoietin erythropoietin stimulates the actual red bone marrow and drives red blood cell production you need tons of nutrients from your git you know what the three essential ones are that you have to know one is iron the other one is b12 and the other one is foley also known as b9 these are essential in actually helping you to make red blood cells then if we're exposed to particular drugs there's so many we'll talk about a few big thing alcohol or you're exposed to nasty toxins they can actually suppress the bone marrow and inhibit the bone marrow from being able to produce red blood cells that's really important the next thing that's also really important for the production of red blood cells is just the intrinsic bone marrow function if somebody has some type of damage to the red bone or they have a cancer they have some type of destruction from like chemo radiation or they have like a cancer where their bone marrow cells just suck and they aren't functioning and making red blood cells that's a problem so here's how i want you to think about anemia anemia is the low number of red blood cells therefore a low hemoglobin and a low hematocrit we'll write that down a little bit but that's what i want you to remember for anemia when a person has anemia they're not making as many red blood cells right now the way we can actually kind of really dig down into the details of anemia is anemia comes down to two different like subtypes you're either not having enough red blood cells hemoglobin and a good hematocrit inside your bloodstream for two reasons one is your bone marrow socks or you're not getting enough hormones nutrients or you're exposed to a lot of drugs and toxins and what happens is if any of those things are present and your bone marrow stops working or stops functioning properly can it become go from a myelinated stem cell to erythroblast to reticulocyte to red blood cell no you know it's really interesting at this stage here right here if we zoom in on it going from a reticulocyte site to a red blood cell it's about one to two days and so that's actually really important because this cell here the reticulocyte actually is a good indicator we can actually test this to see how well the bone marrow is actually functioning so what i can do is i can check the reticulocytes think about this if we have low t3 low t4 low erythropoietin low levels of these nutrients lots of these particular drugs and toxins suppressing the bone marrow or the bone marrow is destroyed it's failing it has it's cancerous and it's not working think about what will happen to the production of reticulocytes will it go down yeah so if the reticulocytes go down then subsequently these will go down but we'll pick this up earlier so we can check something called a reticulocyte index and that stratifies my two different types of anemia into a decreased production due to this issue or something else what is that something else glad you asked what if the bone marrow is working no problem you got normal thyroid hormone you got normal epo you got normal nutrients you don't got no drugs no toxins there's no problem with the bone marrow it's working well and it's producing red blood cells right but the red blood cells get into the dang bloodstream and unfortunately you lose it why i don't know maybe because you end up with a gi bleed maybe you bleed into your retroperitoneum maybe you end up bleeding into your chest cavity maybe you're getting frequent blood draws because you're in the icu and or in the hospital and they have to take and do blood draws every single day and they're just taking and draining your blood every day or you just got some type of surgical procedure that's ways that you're losing blood if you lose blood you lose red blood cells what think about negative feedback mechanisms man right if we have low numbers of red blood cells what do you think that'll do to this myeloid stem cell it'll say hey we're low on red cells since you're functioning well guess what i need you to go ahead and start amping up production and jack that up and make more red blood cells more reticulocytes and so their ticks will bump up if the bone marrow is working so that's important so one of the reasons we could have anemia low hemoglobin low hematomatic or lower blood cells is because we're losing blood and again we'll talk about this for tick index in just a second but we're already kind of getting an idea that it should be higher because why the red blood cells are low if the bone marrow is working all these things are good the bone marrow should compensate and make more red blood cells because you're losing them if it's the other end of the spectrum where you're not losing them you're just chewing them to pieces they're getting into the vasculature and they're getting chewed up they can get up and chewed up in two ways and we'll talk about it in more detail for right now they can get chewed up in the vasculature there's many different reasons why i can get you up in the vasculature or it can get chewed up in the spleen when it happens in the vascular we call that intravascular hemolysis when it gets chewed up inside of these things called splenic macrophages inside of the spleen it's called extravascular homolysis but either way what are we doing we're chewing up the red blood cells dropping the number of red blood cells if the bone marrow is good these things are present what will happen the bone marrow should compensate and say got to make more red blood cells so what do you think the ratic will happen it'll go up for the reticulocytes but you got to figure out why you're hemolyzing and we'll go through and figure out all the different causes for that right but that's the big thing so to put it all together comes down to two different types of anemia anemia due to a decreased production if it's a decreased production what could be the issues it could be decrease hormones thyroid epo decrease nutrients decrease b12 folate and iron it could be due to lots of drugs and toxins exposure think about alcohol is a big one or it could be due to a decrease in the intrinsic bone marrow function due to cancer due to it being destroyed because of a chemo radiation or something like that if that's the case the bone marrow is under producing therefore it's not going to make a lot of reticulocytes the reticulocytes will decrease the reticulocyte index is a it's a formula it's not worth remembering just what happens is the reticulocyte index is based upon your reticulocytes and your hematocrit and something called a maturation factor what i want you to remember is the reticulocyte index and under production means that my bone marrow is not working very well because of one of these issues so will i have a lot of reticulocytes no they're going to drop so my reticulocyte index will drop but we like to use a particular percentage that i want you to remember it'll actually drop to less than 2 and that's important in the other end of the spectrum what if it's due to an increased loss i'm bleeding losing blood and then my reticulocytes are having to be i'm actually causing my bone marrow to compensate if it's working all these things are good then my bone marrow is going to jack it up and produce tons of red blood cells it's going to try to and if that happens what would happen to the reticulocyte index it would go up and so if the reticulocyte index increases that would be more suggestive of a loss or a destruction problem if the bone marrow's working and all these things are good okay that's the caveat here and we say technically it's when it's greater than two percent all right my friends that will cover the basic life cycle and i think it helps us to stratify these two different types because now we got to do is we got to figure out anemia how do we figure out the anemia that's due to decreased production we got to figure out all these issues and we're going to talk about that now what kind of tests and things that we go through all the algorithmic steps then after that we got to say okay how do i figure out which type of issue it is here for the actual destruction loss and we'll go through all the systematic steps for that and lots of case studies all right here we go so we're going to talk about these types of anemia specifically with the decreased production issue now when we talk about these one of the big things that you want to think about here so we know it's a decreased production so we know it's a problem with hormones nutrients drugs toxins or intrinsic bone marrow dysfunction right that's what we have an idea of so think about those things under your differential but before we even start kind of going down that rabbit hole again quickly what is anemia because now we're going to start talking about that a little bit with anemia it is a low oxygen carrying capacity right and usually the best way to define anemia is whenever you have a decrease in your red blood cell mass and specifically we say there is a decrease in the hemoglobin a decrease in the hematocrit and technically in some situations in most cases there is a decrease in the number of red blood cells that doesn't always hold true in every single type of anemia i would say out of these three these are going to be the most important one but for the most part it's usually all of those if they're low it's suggestive of anemia okay so we have anemia once we determine there's anemia low hemoglobin low hematocrit low red blood cells then we've got to say okay is it due to an under production or an increased destruction slash loss problem how do i do that in a perfect world you can check a reticulocyte index so you order the reticulocytes it's a separate order when you order the reticulocytes you get the number back you put it into that reticulocyte index equation and you spit out a percentage we said if the reticulocyte index comes back as less than two percent it's a decreased production problem yeah and if it comes back at greater than two percent in a perfect world it's an increase in destruction like in hemolysis or it's a increase in loss such as in bleeding and patients who were talking about this problem decrease in production in a perfect world the reticulocyte index will be less than two percent don't forget that so order your ticks boom stratify this now you have a person who has some type of decreased production problem and again this isn't a perfect world that's not always the case in true clinical situations after you do that in the cbc there's something called the mcv the mean corpuscular volume mean corpuscle volume just tells you the size of the red blood cells and that helps you to determine which type of underproduction type of anemia we have if the mcv normally normally it's 80 to 100 femtoliters and that's in like a generalized number it can vary all the time but that's a generalized number so if the mcv is low less than 80 we call that a micro acidic anemia okay so we'll put here on the side a low mcv if it's actually going to be normal mcv so it's between 80 to 100 that is a normal acidic anemia and then if it is a high mcv greater than 100 femtoleaders then this is a macrocytic anemia and that would be the last one that we talked about so now we have the three types that we're suspicious of okay now we've got to say okay what kind of tests what kind of things should i be thinking about for a patient who has a microcytic anemia differential don't forget these i want you to keep remembering these maybe you have to repeat it a couple of times iron deficiency anemia anemia of chronic disease thalassemia citroblastic anemia okay again iron deficiency citroblastic anemia chronic disease and thalassemia those are your differentials how do i figure out which one it is the first thing i think that's actually somewhat beneficial okay is to just kind of like write these three out here so let's write these kind of general well actually what i like to do is like to check something called an rdw but we'll get into all these things i'm going to talk about in sequence usually the way it's easily kind of defined is you check a bunch of different tests so here's what we're going to do we're going to check a bunch of different tests the test that i will order for these patients is i will look at i'll check their rdw i will check their red blood cells i will check what's called their mensers index i will check iron studies and then i will also look at what's called a peripheral blood smear and then i'll also take into consideration their history but these are the basic things that i'm going to test all right once i check all of these things i can kind of start going into my different types here so now i'm going to have iron deficiency anemia okay so iron deficiency anemia that one being first when i think about this one when i look at the rdw one of the big things is rdw tells me like the variation in size of the red blood cells and whenever somebody has iron deficiency anemia they typically have a high rdw so that's not the first thing that i'll look at i get that from my cbc as well so an iron deficiency anemia one of the big things you'll see a patient who has a high rdw the red blood cells are typically low okay so they have a low number of red blood cells okay and obviously with this patient having anemia the next thing is i'll look at my mincer's index all the mensers index is if i write it up here all the menstrual's index is is you're taking the mcv divided by the red blood cell number and that should give you kind of that mensers index and there's this is helpful in a condition that we're going to talk about a little bit called thalassemia the menstrual's index and iron deficiency anemia is somewhat helpful and what i want you to just remember for right now is the mincer's index is greater than 13 i promise this will make just sense in just a second but for right now just remember that the next thing i'll do is i'll check my iron studies right so my iron studies you get a bunch of different things from the iron studies what are some of the things that you get from iron studies from the iron studies you'll get a couple different things you'll get what's called iron obviously you'll get something called ferritin you'll get something called the tibc and the last thing you'll get is something called a transferrin saturation out of all of these this can get kind of complicated with all these different types of anemias and i feel like it can be way too much to remember so you know what i like to do i like to kind of make it a little bit more simple and i only utilize this one and this one i think all the other ones are kind of like a little bit more complicated and they just kind of like confuse me sometimes and then i end up trying to remember things and memorize and it doesn't really work so the easy way to look at these is look at the ferritin and look at the transfer and saturation that's what i kind of look at and that usually can help me to differentiate what i got here so in iron studies what you want to look at is ferritin ferritin is kind of like your it tells you it's a protein that binds to iron inside of our cells so it kind of tells us about our iron reserves generally in a perfect world on your exams the ferritin is usually low okay in a perfect world that's not always the case so remember that but in a perfect world the ferritin is low then the other thing is the transfer and saturation you know how we actually get transfer and saturation transfer and saturation is an equation that utilizes it takes iron and divides it by the tibc okay divides it by the tibc generally the tibc in iron deficiency anemia patients is high and then usually iron is low so if you look at this kind of like number here i guess it should kind of ding off a relatively obvious thing you have a low numerator a high denominator the overall percentage is going to be low so you'll have a low percentage so in these patients they'll have what's called a low transferrin saturation and that's really the only time i think this is actually the beneficial component of the iron studies other than that i don't really use the iron studies other than that just for kind of like my iron deficiency anemia i don't think it's really helpful for that it may be a little bit helpful in other kind of diseases but not super great so that's what i get from there peripheral blood smear it's not super helpful so i don't actually get a lot from my peripheral blood smear on my iron deficiency anemia all right boom next one what do we say we have iron deficiency anemia then what else did we say we said anemia chronic disease so anemia of chronic disease when i look at this one i can look at the rdw the rdw actually doesn't really help me it's usually like relatively normal so that's not a super beneficial thing my red blood cells are usually low my mincer index doesn't actually really help me so i'm going to get rid of that part one of the things i do think is somewhat beneficial in a perfect world for anemia chronic disease from the iron studies is that their actual ferritin levels tend to be relatively high so that is one thing i would actually take a look at and the reason why and the most basic concept is when someone has an anemia of like a chronic disease it's usually an inflammatory disease and the liver the ferritin is actually an acute phase reactant protein so it's released whenever there's lots of inflammation and an anemia of a chronic disease due to inflammation it's going to cause the liver to make a lot of ferrotin so ferritin levels tend to be high the transfer in saturation the tibc all that stuff that can be variable so i don't really want to get too much into that just look at the ferritin but the big thing is their history that's what really cues you off in this one the labs aren't super super helpful it's more their history that leads you off to it sometimes what you can do whenever people are confused between this one and this one you can check like a soluble transfer and receptor sometimes that's helpful i don't actually think it's usually necessary and it's usually an expensive test i wouldn't worry too much about that one okay i think that's the big thing peripheral blood smear also relatively unrevealing big thing here i think that's key here is looking at your history that is like the huge component here that you have to look at and usually it's kind of like an exclusionary component all right the next one here we said is thalassemia so thalassemia is a really interesting one so what i would do is i check the rdw the rdw can actually be somewhat high but it can also be normal so i don't really think it's super beneficial in this condition to be honest with you what i do think is actually helpful here is you know what classically the red blood cells tend to be relatively normal so that's an important component to remember the red blood cells tend to be normal now this is where that menser index actually comes in handy the menser index is really really good for this one this one i want you to remember for thalassemia especially in these cases is we said the menstrual index is the mcv divided by the red blood cell in thalassemia these patients mcvs are super low what i want you to remember i want to put it down in just a second but their mcv's are typically less than 70. so if you see an mcv less than 70 and a mincer index less than 13 percent be potentially thinking about thalassemia especially if they have history okay so from there i want you to remember that they'll have a super super super low mcv and their red blood cells are normal so they'll have a super high a super low den enumerator and therefore their overall number will be really low so their mincer index will put their menser index is going to be less than 13 it's a really important thing to remember there okay next thing is my iron studies they're usually not very helpful okay because they can be like relatively normal so they're not very helpful for the iron studies i wouldn't worry about those too much the peripheral blood smear can actually be somewhat helpful so for these patients the peripheral blood smear may show something called basophilic stifling and that's not patho mnemonic for thalassemia but it's something that if you see in the clinical vignette where you have a patient who has a very very low menstrual index they also have basophilic stipeling and they have a history that's the key thing look at their history i want to add that on here plus history i'm going to put ajax their history that's another key component that you need in their workup and they have history so in other words they have a positive family history maybe their family history they have like a person who has thalassemia or they have like a mediterranean ancestry they immigrated from somewhere look about that in the clinical vignette however the most important thing that we did not add but i'm just going to add it on usually as a specific diagnostic tool if you see these things a really low mincers high you know high rdw to a normal rdw not very helpful you see some basophilic stifling you have history you're concerned for it you can confirm and get what's called a hemoglobin electrophoresis and this will usually cleanse your diagnosis before actually having somebody who has potentially a thalassemia okay all right the last one here within these is going to be citroblastic anemia so citroblastic anemia is basically a problem where you don't have you don't are able to use the iron that you actually have because they're kind of like stored with inside of your red blood cells they're kind of just locked within them okay and this is usually due to medications and drugs all right this one is usually a genetic defect of a globin chain so an alpha chain or a beta chain this one's usually due to a lot of inflammatory diseases and this one's due to a deficiency in iron right so it's pretty straightforward but in this situation with citroblastic anemia when you check their rdw it tends to be high so that may help you so you can already see i would say the big ones to remember is citroblastic iron deficiency for the rdw not very helpful for these two next thing for the citroblastic is your rbcs they are usually low next thing is check your iron studies are they going to be helpful not necessarily to be honest with you they don't really give you a ton of information so i wouldn't really look at those too much to really kind of determine which one these are peripheral blood smear is where i think it's going to be the key component in helping you to determine this what i would look at in the peripheral blood smear is you can get two types of things you can sometimes see again just like you saw over here with thalassemia basophilic stifling that's why like not it's not always like the case that oh basophilic stifling is thalassemia no you can see this in a bunch of other diseases what i think is important though for the basophilic stipeling is one of the causes of citroblastic anemia is lead poisoning and so if you see in the case like a patient who's like a little child and was like exposed to paint or something like that check a lead level and see if that's elevated especially if you see basophilic stipeling and signs of citroblastic anemia but i think one of the telltale signs and the giveaways in your actual exam is they'll maybe show you a blood smear i'm going to show you guys some case examples but they'll show you a blood smear and it'll show something called citroblast and this is basically these cells that have like these like bluish dots all within them and it's all the iron that's just accumulated with inside of the actual cell and so that's one of the big things if you see citroblasts sometimes they even have what's called papanheimer bodies don't worry about that i think citroblast is the big thing what you need to do though is if you see citroblasts you need to get a bone marrow biopsy to confirm that's the only way that you can truly like confirm citroblastic anemia is if you see the citroblast on peripheral blood smear you need the bone marrow biopsy to confirm this is the way that i would go about these types of conditions and again history usually for the history here for the history look at medications so exposure to lead lots of alcohol use certain medications that can trigger this there's lots of medications for citroblastic anemia but again these are the things to think about here in your differential all right we covered your microstatics we'll do some case examples in just a little bit to see if we can test your knowledge let's move on to normal acidic anemias so for normal acidic anemia we said it has to be within the 80 to 100 femtoleader so within the range we're now within the range of someone having 80 to 100 femtoliters for their mcv so with normal acidic anemia what is the differential here okay it's a little odd but with these patients what you actually want to do first is sometimes in patients who have what's called iron deficiency anemia you're like wait zach you just said it was from microcytic yes and patients who have early iron deficiency anemia they can actually have a normal acidic anemia so what i do for these patients for normal acidic anemia the first thing i'll do is i will check an iron level i will actually check iron studies and the iron studies will be helpful because what they'll help me to do is see if i have an iron deficiency anemia and i can still use all of these kind of tools here but i'll check my iron studies the next thing i'll do is i'll check for a b12 level i'll check a folate level because sometimes early uh b12 deficiency and folate deficiency can also cause a normal acidic anemia you'll see here in a little bit that b12 and folate usually cause macrocytic anemia but if it's early it can actually cause this first just like iron deficiency anemia normally causes a microacidic but in the early stages of iron deficiency it can cause a normal acidic okay i'll check these things after i do the iron studies the b12 the folate the next thing i'll do is i'll check potentially some other organs them to see if they're a little jacked up so the ones i'll look for is i'll check my thyroid function because that was one of the organs there so i'll check my tfts i'll also look at liver function so i'll look at lfts and i'll also look at kidney function so i can look at a bmp okay and again look at their history obviously if they have like a in stage or chronic kidney disease that could be potentially obvious okay and then we'll talk about something else that's really important here in just a second and these patients that also have i've gone through these and i've looked to see if they have any liver any kidney disease any type of thyroid disease and all of that's relatively normal the other thing i can consider potentially is is there any hemolysis but we'll talk about that a little bit more later in the actual increase in destruction loss so you're probably like wait zach i thought hemolysis that's always going to be a retic index greater than two percent you said that if it's less than two percent it can't be hemolysis that's not necessarily the case and here's why it's a little caveat in the in the boards it will be like that it'll likely be heretic index greater than two percent it's hemolysis in the in an actual clinical situation sometimes people can have an underlying like bone marrow disorder where they're not actually producing an adequate number of red blood cells let's say they have iron deficiency anemia and then all of a sudden they develop a hemolytic anemia on top of their underlying iron deficiency anemia well they're they're actually going to have destruction of red blood cells that'll try to tell the bone marrow to make more red blood cells but guess what the bone marrow is not working well because they have iron deficiency anemia and so the production of reticulocytes will still be low and so that's why sometimes you can still have hemolysis in a normal acidic anemia i'm going to put it in there but remember we're going to talk about it more in this actual increase in destruction loss process so put hemolytic labs you'll also order that as well the last thing that you consider in these patients is what's called a bone marrow biopsy and again we'll talk about that okay so when you go through these these are the things that you want to check okay you check your iron studies if you check your iron studies let's say and you obviously have this super obvious let's say that you check the iron studies and you think that they have iron deficiency anemia what would you look for you would see that they would potentially have a very low ferritin and they would have a low transfer in saturation that's a pretty obvious thing there okay you know what else is really interesting for the iron studies not only do they help you to determine if you have iron deficiency anemia okay so these can help you with iron deficiency anemia they can also say is there any anemia of chronic disease you're probably like zach you just said anemia chronic disease can be a microacidic anemia it can but it can also be a normal acidic anemia and again it depends upon the history so you got to look at the history do they have ra do they have sle do they have a malignancy do they have chronic kidney disease check those things but if they have anemia chronic disease what do i tell you would happen with that ferritin it's usually pretty high again that's not always perfect but it can help you somewhat okay and again with these patients both of them can have low iron okay and their transfer and saturation for anemia chronic disease it can also vary a lot but again something to think about then for the b12 and foley you want to see if the b12 and folate is low so if the b12 is low okay we got b12 deficiency if the folate is low which is also known as b9 then it's we it's it's folate deficiency but sometimes you can get a little tweener okay sometimes if it's not this one or this one you get a weird situation where you have a what's called a borderline low b12 and folate where it's just that the end up like the lower limit of normal if that's the case what you order here is you order something called a methylmalonyl methylmalonic acid and you order something called a homocysteine level in these situations if it's borderline low you're not sure which one it is if it's true b12 deficiency the methyl malonic acid will be elevated and the homocysteine will be elevated if it's a b9 or folate deficiency the methyl malonic acid will be normal and their homocysteine levels will be elevated okay so that's an important thing to remember so we check our iron studies we check our b12 and folate for early iron deficiency anemia early b12 foley deficiency anemia also consider anemia chronic disease but what i tell you is really important here history my friends that's the most important component here check your tfts if you have low t3 low t4 what do you think it is hypothyroidism oh man you're good what if you have increasing lfts increase asd increase alt increase um other different like types of liver enzymes maybe a drop in their albumin and increase in their inr it could be liver failure related that's important if it's bmp do they have an increase in their bun do they have an increase in their creatinine it could be ckd so they may have chronic kidney disease sometimes i don't suggest it but sometimes the literal chair will say if they have ckd check like an epo level remember erythropoietin was the driver for red blood cell production if the kidneys are failing can they make ippo no so what would you think the epo levels would be low so sometimes you can do that sometimes they suggest not necessarily doing that hemolytic labs we're going to talk about this more in destruction and loss you still want to check them because you can have this believe it or not we're not going to go through it now i'm going to put just c above we're going to talk about that a little bit later okay the next thing that you also want to consider for these patients here is would i ever get a bone marrow biopsy why would i ever do a bone marrow biopsy remember i told you that if it's a problem it's a nutritional it's a hormonal it's a drug or it's an intrinsic bone marrow issue normal acidic anemias typically tend to be bone marrow issues if you think about these ones usually if it's an intrinsic bone marrow problem it's likely normal acidic so here's what would t like cue you up to say oh shoot this could be an intrinsic bone marrow problem i would consider a bone marrow biopsy and this is where i'm i'm telling you please listen here if my reticulocyte index is like super low like non-existent i'm talking like 0.1 percent so it's less than two but it's like almost zero if that's the case like 0.1 percent that's a concerning sign another thing is what if they also have what's called pan cytopenia you guys know what that is i know you know what it is low red blood cells low platelets and low whites like white cells all the cell lines are dropped if that's the case something is wrong with the bone marrow if i am basically making no red blood cells no reticulocytes that's super concerning for a bone marrow problem and if other cells are being affected that's super concerning for a bone marrow problem biopsy the bone marrow and sometimes what this can show you is three particular types of conditions one is called aplastic anemia in this situation if you check their bone marrow biopsy they're like they like make no cells all their cell lines are dropped and so what you would see is we're going to just kind of look here low proliferative bone marrow biopsy you can check for something called mds myelodysplastic syndrome in this situation they're producing lots of blast cells that don't actually have any room to allow for any red blood cells platelets or white blood cells to be produced and so they crowd out the bone marrow but you're still having low levels of all these cell lines and lower ticks so again in aplastic lower ticks and pancytopenia mds low vertex and pyoncytopenia but if you look at the difference here they have a hyper proliferative bone marrow filled with lots of blast cells immature cells the last one is the most rare one and weird one called pure red celloplasia and this there is no pancytopenia so here let's do this none of that only in the super obvious low reticulocyte count you get a bone marrow biopsy and you check and they have low erythroblasts so their red cell line is the only one that just pretty much stinks if that's the case it could be suggestive of pure red celloplasia a lot of things to think about with this one i promise i know it seems like a lot but we're gonna do some practice problems to make sense of it but these are the things that i want you guys to be thinking about when you're having a patient who comes up with a normal acidic anemia let's hit it home with macrocytic all right macrocytic anemia so we checked our mcv and it is greater than 150 liters right so we have some big big honking cells so high mcv greater than 100 femtoleters okay when we do this one we got to think about our differentials for this one all right so the way i think about the differentials is again i think about the test that i need to order it just helps me to categorize it in my brain so for macrocytic anemias i want to check i would like to check first off a b 12 a folate level then after i do that i like to look and since i'm ordering labs i might as well just add some other labs so i'll add in some thyroid function tests i'll add in some lfts i'll look at their meds and i'll also check a blood alcohol concentration if they're not telling me the truth about their alcohol history after i do that i also consider some other particular things maybe like a peripheral blood smear also can be somewhat helpful lastly i usually don't actually like get to this point where i think it's absolutely necessary unless there's something super super concerning but you can sometimes consider a bone marrow biopsy i would put plus or minus there and kind of remember it's easier to remember for normal acidic but you can potentially have some bone marrow problems with macroacidic anemia all right but this is kind of like the cut and dry way that i go about ordering these tests so first thing is i got the b12 and folate why because b12 and folate deficiency it's easiest to remember that they're macroscience but don't forget that they can cause early and their early disease is normal studies just like iron deficiency is microacidic in the early diseases it can cause normal acidic when i check the b12 and foley this is going to be a reminder guys what did i say you check the b12 level it's low you're diagnostic if it's you check the folia which is also known as b line it's a b9 it's low it's diagnostic but if i have a patient who has borderline it's just on that lower limit of normal of their b9 their folate and their b12 and i don't know which one it is what can i do you can obviously look at their history but i can check for the b12 deficiency typically i look at the methyl myelinate malonic acid and the homocysteine levels and the same thing for b9 or folate deficiency i look at the methyl malonic acid and the homocysteine levels in a perfect world this for b12 is elevated for both of them and for b9 the mma is normal and the homocysteine is elevated okay boom i figured that one out for the thyroid function test i'm looking for a low t3 and a low t4 for my lfts i'm looking for increases in lfts and remember this could have a patient who has also a history look at their history sometimes you don't even need these tests you can actually look at their history and they have diagnosis of our hypothyroidism maybe they're not taking their meds or they're not at a proper dose they have a history of cirrhosis right something of that nature and they continue to do things that they're not supposed to be doing worsening their disease look at their medications and so when you look at their medications there are so many different medications i think sometimes on the boards they will actually try to have you remember certain ones and so the things i would potentially consider here is some of the meds like you're kind of like the keem somewhat of the chemotherapy things where they impair dna synthesis or replication methotrexate is definitely one of them another one called 5-fluorouracil another one called hydroxy urea is a big one now you can utilize and a patient who has um a sickle cell anemia other ones are any kind of like hiv meds but more specifically like the protease inhibitors like xydovidine another one here would be like antibiotics the specific antibiotics i would remember here is what's called trimethoprim sulfamethoxazole also known as bactrum another one is your anti-seizure meds and so your anti-seizure meds like phenytoin and valproic acid are really big ones as well here's the big mama though if they have a history that's positive for alcohol use heavy alcohol use that could be also a very important medication to be thinking about as well if maybe you're uncertain there's questions that they're actually not telling the truth you can look for an elevated blood alcohol concentration to verify that maybe they are a heavy drinker and they just drank recently or something of that nature okay these could be somewhat helpful in your diagnosis now the peripheral blood smear so what you can actually do is some of the actual literature will actually say you should order this first to really determine how you're going to test somebody which can somewhat be helpful in stratifying you can remember this i would say just in general remember this one component of it from the peripheral blood smear when you get a peripheral blood smear you want to determine if they have what's called megaloblast so macros like megaloblastic macrocyte acidic anemia or non-megaloblastic macroacidic anemia and so the way you do that is you get a peripheral blood smear and you look to see if they have what's called megaloblast megaloblasts so megaloblasts is basically you're looking at the neutrophils and when you look at the neutrophils usually they have like a couple lobes like three lobes generally normally but in these patients who have a macrocytic anemia which have megaloblasts usually it's b12 foley deficiency some types of medications or alcohol they can impair the dna synthesis in the maturation process and they can cause like multiple lobes so if they got greater than like five lobes we sometimes call these hyper i'm going to abbreviate hyper segmented neutrophils that's megaloblastic and you should have a high degree of suspicion for b12 foley deficiency or some type of medication or maybe even like alcoholism those would be big things to think about and it would make it easier what tests you can kind of order and which ones maybe you don't have to get right now so that's one of the big things is is it positive for megaloblast or is it non-megaloblast and megaloblastic macrocytic anemia in other words they do not have this above issue there so in other words they don't have greater than five lobed polymorph nuclear leukocytes or neutrophils so they don't have hyper segmented neutrophils so in these situations they are negative for hypersegmented neutrophils more likely suggesting like a thyroid issue a liver issue or maybe some type of underlying bone marrow problem okay and sometimes even drugs and medications as well the bone marrow biopsy my friends i would again i would caution to potentially not always be right up front with this one i think if you have a patient who you see potentially like pancytopenia so you have any concerns and they have pancytopenia low red cells low white cells low platelets it might not be a bad idea to potentially get a bone marrow biopsy because this may tell you if you have something called myelodysplastic syndrome and with myelodysplastic syndrome they would have pancytopenia and again if you looked at that bone marrow biopsy what did we say would happened you'd have a high like a high proliferative type of bone marrow with tons of blast crowding out the actual bone marrow and not allowing for red cells and white cells and platelets to be produced adequately and so that could actually also cause a macrocytic anemia sometimes even say multiple myeloma but i would kind of just keep it simple with these and if you really have the extra brain space maybe consider this one but these are the things that i want you to remember for your work up and how to systematically approach your different types of anemia is due to a decreased production issue so what we can do now is we can actually take a look at a bunch of case studies practice do some space repetition and see if all of this stuff makes sense and if you're able to solve some problems and give you guys some confidence when you see these cbc's and you have to interpret it so let's get to it all right so let's go through our case studies guys and really put to practice everything that we just talked about on the board because it was a lot and i want to make sure that you guys feel comfortable with this all right so first case this is going to put to practice everything we talked about keep that systematic approach ready 26 year old female past medical history heavy menstrual periods hemoglobin 9.6 she's anemic we got to determine if it's a decreased production or increased destruction loss how do we do that we're tick index for tick index is less than two it's under production if it's greater than two it's increase destruction loss let's see what it is it's less than two under production from an under production point you have to then check the mcv to see what kind of acidic it is normal micro or macro we checked the mcv it's actually 75 that's less than normal so it's a microacidic anemia if it's a microcytic what's the differential iron deficiency anemia thalassemia citroblastic and anemia chronic disease after we do that we check our rdw our red blood cells and sometimes you can calculate a menstrus index boom rdw is high that's potentially suggestive of iron deficiency anemia but you can also see this in citroblastic anemia red blood cells are low and the menstrual index is 15. that kind of tells me that it's unlikely thalassemia since thalassemia is usually less than 13 percent okay next part is i check my iron studies ferritin is low whoa what did i say when ferritin's low automatically have a high degree of suspicion in a perfect world that it's iron deficiency anemia and then the transfer and saturation is also low how do you calculate that you take the iron divided by the tibc iron is low usually iron deficiency anemia and tibc is usually high so that's why you should have a low transfer in saturation very very likely that this is basically an iron deficiency anemia and usually the peripheral blood smear which is the last test that we can get is usually unrevealing it's not telling me very much i think this is iron deficiency with very strong confidence okay move on to the next one case two we got an 85 year old female history of sle presents with hemoglobin in 10.2 she's anemic check there were tick index it's less than two under production so now we got to check the mcv mcv is 75 that tell me that it's a microcytic it's one of those four what do i do again i gotta check my rdw my red blood cells and sometimes my menstrual index i check my rdw it's normal unlikely iron deficiency anemia unlikely citroblastic anemia could be potentially what anemia chronic disease or thalassemia red blood cells are low usually they're normal in thalassemia let's pretend that i put the mensers index in here and this patient the menstrual index is actually 16 let's just say so it's unlikely thalassemia so we're kind of potentially thinking this could be anemic chronic disease plus what did i tell you to do after this get your iron studies iron studies ferritin's high what i tell you was one disease i think is actually relatively important to remember that ferric kidney can be very very high especially if there's a chronic disease anemia chronic disease so ferritin is pretty high and plus this person has a medical disease that would actually put them at risk of having a lot of inflammation to cause that ferritin to go up okay next thing i could do is a peripheral blood smear is it going to help me with anemia chronic disease that i have a high suspicion of no so therefore i think that this is anemia chronic disease because it fits well with the presentation history and labs okay next one three past medical history of a guy who has tb exposure got treated with isoniazid he's got a hemoglobin 8.9 he's anemic what do we do check her tick what's the retic less than two under product under production check the mcv if the mcv is there what do we think this is a microacidic if it's a microcytic it's one of those four what do we always do rdw red blood cells mensers and this person the rdw's high potentially iron deficiency or citroblastic red blood cells are low let's just tell you that the menser is again greater than 13 percent unlikely thalassemia unlikely iron deficient i mean it could be iron deficiency it could be citroblastic anemia we don't really have a strong understanding if it's anemia chronic disease just yet what do we do iron studies they're normal that kind of tells me that it's not iron deficiency anemia and it also tells me that it's not likely that this person has anemia of chronic disease but again there's nothing like super special about this what's the next thing i need prefer blood smear look at the birth bloods mirror guys what do you see these things oh those are your citroblasts this is a slide that you definitely have to be able to recognize if it's citroblast we have to confirm with a bone marrow biopsy but this would tell me that this is citroblastic anemia and you guys are on a roll all right here we go case study four 34 year old female mediterranean ancestry who has been treated with iron supplementation for a while and still has a hemoglobin of 9.5 despite that what do we do for tick index it's less than two under production mcv 65 oh what i tell you to remember if you've seen mcv less than 70 to have a high degree suspicion for thalassemia check the rdw check the red cells and check the mensers rdw's normal it kind of tells me that's unlikely iron deficiency and citroblastic potentially red blood cells are normal that also made me think about thalassemia and the mensers is less than 13 percent that makes me think about thalassemia what do i do iron studies they're unrevealing again not very helpful for the thalassemia patient usually the relatively normal peripheral blood smear what can we see sometimes you can see basophilic stipeling in these patients you guys see like there's like these actual like little blue dots around these like red blood cells here some of them have some basophilic stipeling and like in this one here as well and then this one here that would be potentially something to think about that you could see in a person who has thalassemia but it's not pathodemonic we definitely need to cert like completely diagnose it we need history they have a mediterranean history that's possibility i would need a hemoglobin electrophoresis i get it and it's positive what's my diagnosis thalassemia all right five we have a 50 year old 54 year old female past medical history seizures treated with phosphoenotoin and had a recent uti she was treated with bactrim which is trimethoprim sulfamethoxazole and she comes in with a hemoglobin of 8.6 she's anemic all right what do we do check the retic it's less than two under production we check the mcv determine if it's micro normal or macro oh that's macro macro acidic what do we think okay we always should check a b12 we should check a folate we should look at their meds look at their alcohol look at their tsh look at their thyroid functions look at their lfts and then if we're super concerned we can also do a peripheral blood smear lastly we can consider a bone marrow biopsy we're going to do these in order right all right so what do we do check the b12 and folate first they're normal kind of rules out that they have b12 and foley deficiency will be the other ones look at their medications look at the alcohol look at the thyroid functions the liver functions let's do all that tfts are normal lfts are normal blood alcohol concentration is normal and they have no history of alcoholism okay what also i gotta look at look at the meds i look at the meds is there any one of these meds that concern you do you see anything bactrim trimethoprem sulfur methoxazole and then this is actually phosphoenotone it's one of the actual brothers or cousins you can say a phenotone so there's a possibility that these two drugs could have possibly done what they could have actually caused this anemia and then again we look to see the actual peripheral blood smear sometimes it can be helpful sometimes not again you can get that peripheral blood smear to see if you see any hyper-segmented neutrophils suggestive of megaloblastic anemia what did i say in the perfect world megaloblastic anemia suggest if it's present greater than five polymorphonucleosites or white uh neutrophils it's usually suggestive of b12 or foley deficiency in a perfect world but it's not actually present here so it makes you think about all the other causes like thyroid liver medications alcohol stuff of that nature so again likely medication related cause for this patient's anemia a macrocytic type all right here we go next one case six uh 75 year old male past medical history cirrhosis secondary to non-alcoholic fatty liver disease presents with hemoglobin 10.1 he's anemic what do you do check the retic it's low under production what do i do check mcv it's high macrocytic what do i got to do b12 folate tfts lfts medication alcohol peripheral blood smear foley b12 normal tft is normal oh elevated lfts and they have a history of cirrhosis and there was no particular meds in their actual history that was a potential culprit and they don't drink and there was no history of it their blood alcohol concentration is normal okay so i definitely have a likely culprit here that being the cirrhosis we should be consistent though what do we say to check after this peripheral blood smear we look at the peripheral blood smear i didn't tell you guys this on the white board but i'm gonna tell you now sometimes with liver disease you can actually get these special types of like little like pc kind of weird-looking cells here called acanthocytes so these are called a canthocytes and you can kind of see these in patients who have liver disease it's not absolutely like oh you only see it in this disease but it's somewhat suggestive of it so that's something to think about there and again they have no hyper segmented neutrophils so that would unlikely be a megaloblastic anemia it's likely a non-megaloplastic alright so it's likely a liver disease related anemia all right great job seven all right here we go 54 year old female past medical history ckd4 presents with hemoglobin of 8.6 anemic what do you do check or tick it's low under production what do you do check mcv it's low mcv is 85. sorry mcv is normal i apologize 80 to 100 that's a normal acidic anemia you would also want to do what with these again look at your red blood cells they're low what do we do for our normocytic anemias what do they tell you to always check could be early iron deficiency could be early foley and b12 deficiency then after that you also want to check your kidney your liver and you also want to check the thyroid function and then after that you want to check your hemolytic labs if you're absolutely concerned for that but in a perfect world we're probably not going to do that right now because we're going to keep it perfect is whenever hemolysis is something i'm concerned about when the tick is greater than 2. so we're not going to check those and then what do we say was last if we have high concerns of it a bone marrow biopsy possibly right all right so let's go through here so first thing that we should be checking is again iron and b12 folate so we check all of those things we check the iron studies the ferritin is high is ferritin usually high in iron deficiency anemia in a perfect world no it's usually low so the ferritin's high that means that there's likely some type of anemia of chronic disease here what's this ckd that's one of the diseases all right transfer satch is normal folate b12 normal thyroid function functions normal lft is normal no obvious meds in their medical history but they do have a history of chronic kidney disease that's interesting okay what else did i check do i need to do any kind of like bone marrow biopsy no the peripheral blood smear doesn't really show me anything it's likely anemia of chronic disease why because again ferritin's high transference that's normal all the folate b12 iron didn't suggest any iron deficiency anemia no thyroid abnormalities no lft abnormalities they did have chronic kidney disease right ckd was one of those and ckd can actually be a chronic disease that can actually cause anemia chronic disease we actually called anemia of chronic kidney disease and so that's likely the problem here okay if we got like a bmp we'd be able to have evidence that they would have been elevated potentially bu or creatinine or some type of uh decrease in their gfr all right all right case study eight we got a 75 year old male status post chemo radiation for lung cancer presents with pancytopenia what does that mean low platelets low red cells low white cells hemoglobin 7.3 they're anemic what do i do check a retic retic is less than two we actually get it and it's zero point two percent it's barely there oh that's interesting okay well whenever we have a normal acidic anemia what do we always have to check we got to make sure it's not early iron deficiency b12 foley deficiency make sure there's no thyroid abnormalities no liver abnormalities so we got to go through all that stuff first and well actually before we even do that forgive me i went outside of my systematic approach again once you have a tick index less than two it's pretty much very very bad what do we always do again we under production checking mcv normal acidic microcytic macrocytic in this case it's normal acidic now we know it's normal acidic if it's normal acidic we have to confirm that it's actually either early iron deficiency b12 folate deficiency rule out thyroid liver kidney disease and then also potentially a bone marrow problem so how do we do that let's check those labs sequentially what are we going to do iron studies normal folate b12 normal tft is the thyroid function normal cmp which tells me my liver function and my kidney function normal what i tell you was a concerning finding my friends if you see pan cytopenia and a crazy low retic count you got to be concerned about an intrinsic bone marrow problem so what do i really need to do here i probably need to get a bone marrow biopsy and i get a bone marrow biopsy i look at this and i see a decreased cellular picture a low proliferative picture filled with fat tissue if it's decreased proliferative area with a lot of fat tissue deposition that is aplastic anemia and usually aplastic anemia is they have a high epo i don't think that's really worth remembering that's just an extra thing in case you want to remember it all right so let's move into this part now so when we have somebody who has increased destruction slash loss of their red blood cells again we think that they have anemia right so we're kind of starting off that whole anemia part they have a low hemoglobin they have a low hematocrit they have a potential low number of red blood cells we try to risk strata we try to kind of stratify which type they have so we check our reticulocyte index in a perfect world the reticulocyte index would be greater than two percent right so we know that in these patients they would have a reticulocyte index greater than two percent and the reason why we would say in a perfect world is because we're saying that the red bone marrow is blasting out red blood cells because there is a drop in red blood cells because you're either losing them or destroying them but in order to truly have a retic index greater than two percent you got to have an actual functioning bone marrow so that's why i say in a perfect world in your clinical vignettes your cases that you'll get on your boards it's gonna be perfect all right so you have a patient who has a retic index greater than 2 so now you know it's either an increase in destruction or a loss how do i figure out if it's a destruction issue and if when i figure out it's a destruction issue how do i get to the actual underlying problem here because again you got to remember we are taking an approach this is a diagnostic approach to these we're going to have an individual video microcytic macrocytic normal acidic and hemolytic anemias where we go into detail of all these things but i want to introduce you to it so you have an approach to these a basic understanding so it'll really help you when we talk about these in detail so with hemolytic anemias let's start with that the destruction portion so when i talk about hemolytic anemias remember i told you that you could break down the actual red blood cell when you break it down you can break it down inside of the vasculature intravascular or you can break it down inside of this splenic macrophages inside the spleen extravascular either way when you break down red blood cells inside of the red blood cells you break down a very specific there's a lot of different things that can leak out of these red blood cells so say that i break down these red blood cells when i break them down i can release out a couple different molecules that you have to check this is a part of those hemolytic labs that i mentioned in the normal acidic anemia first one that is usually released into the bloodstream because it's released from the red blood cell is ldh lactate dehydrogenase that's usually elevated so it's an enzyme found inside the red blood cell when you pop it open leaks out the other one that also can kind of leak out is bilirubin so you know um inside of the red blood cells you have hemoglobin hemoglobin has a protein component and then it also has the heme component the heme component can get broken down into bilirubin what is really important though we're going to call it billy to tell you it's bilirubin but you know there's two different types of bilirubin unconjugated also known as indirect just so you know they can use it two different ways indirect bilirubin i'll put in parentheses though unconjugated bilirubin is another way of explaining it this will be elevated in these patients so they may have some jaundice-like appearance and an increase in bilirubin it's more the unconjugated or indirect one okay the next thing that you release out here is you also release out the hemoglobin in general so whenever hemoglobin gets released into the bloodstream we don't want it to be by itself it's a nasty little molecule and whenever you release this hemoglobin just it's it's in a vasculature on its own our beautiful liver says oh crap there's lots of this hemoglobin out there guys i gotta fix this and it makes a particular protein this protein is called haptoglobin so haptoglobe and imagine i'm gonna kind of draw him as like a little circle here and then imagine hemoglobin i'm going to draw him as this circle here what happens is haptoglobin will not allow hemoglobin to float around by itself and so hemoglobin and haptoglobin will complex with one another and bind to one another so that haptoglobin can kind of bind the hemoglobin and prevent hemoglobin from causing all types of problems so there's the complex now when the liver makes this haptoglobin and the haploglobins binding to the actual hemoglobin what happens to the free haptoglobin now now that it's complex you're making a ton of this a ton of these complexes what happens to the free haptoglobin that drops because you're complexing it with all this hemoglobin that's leaking out so you'll have low haptoglobin the other thing is some of this hemoglobin actually gets into the urine it actually gets to your kidneys and when it gets to your kidneys you can actually pee out some of that hemoglobin into the urine and so the hemoglobin inside of your urine will also be elevated and so you'll have what's called an increase in the hemoglobin in the urine so many times we call this hemoglobinuria hemoglobin neuria so one of the obvious things that you can test for and a patient who you're concerned you check they have low hematocrit low hemoglobin lower red blood cells or tick index greater than two percent check your hemolytic labs what are those labs ldh indirect bilirubin haptoglobin and you can also order a ua and look for hemoglobin in the urine if you really want to boil this down to the most common two types it's going to be this one and this one these are going to be the biggest ones that you'll probably see in your clinical vignette so you'll check an ldh and a haptoglobin and that will be the big thing for your hemolysis if it comes back positive you have an elevated ldh and a low haptoglobin you can actually say with some relative confidence there is hemolysis now technically if it's inside of the vasculature intravascular it'll be crazy high if it's inside of the splenic macrophages it'll be high but not significantly so what you also want to consider sometimes is you want to take into consideration what's their spleen looking like in some of these patients so maybe they do have some positive hemolytic labs take a look at their spleen and sometimes what i like to just say is look to see if they have any splenic diseases or any kind of liver disease and then you should consider a splenic ultrasound because a splenic ultrasound may show you something called splenomegaly and this is a pretty important thing because splenomegaly may mean that the spleen so sometimes you can have something called hyperspleenism where the spleen just kind of like entraps and yanks red blood cells from your bloodstream way faster and way more than it ever should usually red blood cells get destroyed by your spleen whenever they're old and defective but whenever your spleen is just acting up and there's many different reasons it can do that we're not going to go down that rabbit hole in this video we'll do another one again on its own we'll talk about hemolytic anemias the spleen can just chew through the red blood cells and it can hyperfunction and yank them all out and it can get really big because it's chewing through them so consider a splenic ultrasound when you have someone who has some big splenomegaly and think about that if they have underlying splenic disease or liver disease this will involve a lot heavier workup which we're not going to go into right now but that's something to think about especially with the extravascular hemolysis okay so you think they have heme hemolysis check an ldh check a haptoglobin you can also consider getting a splenic ultrasound to look for any splenomegaly to rule out hyperspleenism got it okay next thing i like to do after i've confirmed so first thing is this this is the first part first part is your hemolytic labs that's the first part second part is is this autoimmune hemolysis so that's the next thing i have to determine so in order for me to do that i have to do something called a direct antibody test sometimes we call this a coombs test and what i want to know is i want to know if my coombs test is positive or negative if the dat or the coombs is positive i have something called an autoimmune hemolytic anemia and again with these there's many different types of issues with these so whenever we talk about autoimmune hemolytic anemia there's an endless number of causes we're not going to go down that rabbit hole what i do want you to know is when you get these tests what they tell you so let's say that you do a dat or a coombs test what you want to know is is it a warm first off you want to know if it's positive okay so if it's positive you have an autoimmune hemolytic anemia but then you got to go to the next step so if it's positive you have an autoimmune hemolytic anemia but then you got to look at a little bit more and determine if it's a cold autoimmune hemolytic anemia or a warm autoimmune hemolytic anemia and the way that you do that is by the way that they're positive on their dat or their coombs test in the warm autoimmune hemolytic anemia their igg is positive and their complements is positive and the cold autoimmune hemolytic anemia their igg is negative and their actual complements are positive so that's something to remember but either way they're both autoimmune hemolytic anemias if you really just want to come down to the simplest point you check for hemolytic labs it's positive you check a dat it's positive if the dat's positive you do have autoimmune hemolytic anemia if you want to figure out if it's hot or cold you just look at the patterns of their igg and their compliments if both are positive it's warm if only the uh igg is negative and the compliments are positive it's cold and that can kind of differentiate like your two different types of autoimmune hemolytic anemias all right so first thing check your hemolytic labs if they're positive good move on to the second part check for the dat if the dat's positive good it's autoimmune look at the patterns is it warm or cold if the dat is negative okay so then the third thing is if the dat is actually potentially negative then you got to go down the rabbit hole of looking for another cause of their hemolysis and so then that's when you try to determine this is how i look at it so if they're that's negative then i try to say okay they're hemolyzing now due to something else that's not auto immune so then i try to think about reasons why someone would actually get the red blood cells hemolyzed is it something wrong with the red blood cell intrinsic intrinsically or is there something else that's actually working against the red blood cell extrinsically so some type of trauma is there some type of infection is that what's going on outside the actual red blood cell that could be affecting it that's the way i look at it so with these it helps me to figure out my testing and what kind of things that we should be thinking about so if my dad's negative i think okay first let's think about intrinsic hemolytic anemias so i think about the red blood cell is there something wrong with an enzyme inside of it if that's the problem the first disease i think about that you guys would probably want to think about here is called g6 pdh deficiency so it's called g6 pdh deficiency in this disease you see this in younger african-american children again in this one it's usually after they've had like an infection they've been exposed to some type of like fava bean like they were eating fava beans stuff like that but what you're looking at for these patients is you actually check this enzyme and this enzyme level will actually be low you only want to check it though when they're not hemolyzing so that's one of the big things like little caveats in this is you only check for g6 pdh deficiency when they're not actually in hemolytic crisis because whatever put them into it you have to wait a little bit so they're a little bit healthier and then you can check the enzyme but what actually may come up on the exam is for these patients a lot when after you get your dad i think the next two big things to look at is your peripheral blood smear and history that's the next thing so i would do that so after the dat's negative the fourth step i would say is look at my peripheral blood smear and look at my history so for this peripheral blood smear what i would actually see for these patients is i would see something called bite cells and we'll show you what those look like and i could also see something called heinz bodies so if i see these i have a concern of g6pdh deficiency if they're not in the hemolytic stage i can check their g6pdh level and it'll be they'll actually have a significant deficiency there all right hemoglobinopathy so if they have um again a history of some type of hemoglobin problem they have a history of sickle cell anemia a family history of sickle cell anemia they've had a history of vasoclusive crises or they're having it right now in that kind of sense you can actually cons potentially assume it's a hemoglobinopathy that's your history but if we wanted to get a peripheral blood smear what would the peripheral blood smear show if you had sickle cell anemia you would see sickle cells and if you actually were potentially maybe this was their first vasoclusive event and you actually potentially got the peripheral blood smear and you saw that there was sickle cells you can actually confirm with a hemoglobin electrophoresis to show sickle cell anemia and obviously that'll show the hemoglobin f all right and in this case you'll actually see like they'll have the sickle cell anemia potentially so again that's your hemoglobinopathy so i think is there an enzyme problem g6pdh is there a hemoglobinopathy sickle cell anemia is a big one look for sickle cells look for the history any vaso occlusive events confirm with the hemoglobin electrophoresis is there a membrane problem so with the membrane problems i think about two disorders here one is called hereditary spherocytosis so with hereditary spherocytosis usually these patients won't be super obvious they won't have a lot of like symptoms or clinical features but again what's the next test peripheral blood smear and history nothing really special about their history but if you look at their peripheral blood smear they will have spherocytes so a lot of these like spherical shaped cells what you'll do is is if you're concerned you can do something called an osmotic fragility test and if their osmotic fragility test is positive you have a very high degree of suspicion for hereditary spherocytosis okay the next disease that you should be thinking about here is actually called paroxysmal nocturnal hemoglobinuria so in this disease it's actually odd because at night they actually kind of go through these hemolytic events and they have particular like mutations in very specific proteins in their cell membranes what you want to look at in their history is they've had some type of history of like clots like lots of actual venous clots maybe they had like dvts and pes or bud chiari syndrome so look for like history of like venus types of clots especially like like bud chiari syndrome or something like that then again look at your peripheral blood smear on the peripheral blood smear they will have spherocytes but one of the key things here is not only will they have a history of venous clots but they'll wake up they'll actually in the morning they'll have dark urine in the am okay so they'll wake up in the morning and they'll have dark urine in the am they'll also potentially have history of venous clots you get a peripheral blood smear it shows spherocytes if you have this high degree of suspicion with some of this history and spherocytes you should consider sending off a very specific test called a flow cytometry so you can do something called a flow cytometry and if that is positive then it's very suggestive of peroxismal nocturnal hemoglobinuria all right so that's the way i would go through that is it hemolysis ldh haptoglobin that comes back positive is it autoimmune datums is that positive okay autoimmune which one warm cold boom if it's negative okay is it an intrinsic problem get a peripheral blood smear and look at their history figure out if it's an enzyme hemoglobinopathy or a membrane problem if you've gone through all of these and you can't find it then move on to your extrinsic problems all right so for these bad boys you can think about something called microangiopathic hemolytic anemia maha and what this is is you're actually having a red blood cell problem but also look for low platelets so the other thing i would actually tell you to look at is what is their platelet count because if their platelet count is dropping sometimes we call these like thrombotic microangiopathies this can actually be sometimes very helpful so if you see a drop in their platelets think about microangiopathic hemolytic anemia the basic concept behind this is that you are actually having some type of like small clots so the basic theory behind this is you have these vessels here and they have like small clots here and as like your red blood cells and as the platelets are trying to kind of like squeeze through like they're getting kind of consumed up in these clots they're actually can get consumed or they can get ripped apart as they're bumping up against these microthrombie the other thing is that sometimes if people have like heart valves those can actually kind of rip they can rip like a mechanical heart valve and you're pushing blood against it sometimes red blood cells can get just get sheared apart on that as well so i think one of the big things to look for for maha is there's a couple different disorders first off look for the low platelets then you want to think about a couple different types of bajas the first ones that you want to think about is dic then you want to think about something called ttp think about hus think about help syndrome and then lastly you want to think about some type of mechanical valve all right so dic has disseminated intravascular coagulation and these patients all of these they're kind of like having like somewhat of these low platelets and low red blood cells because of these multiple micro thrombi in dic some of the cueing kind of features here is that usually the patient is like septic or critically ill and they have like elevated coagulation kind of problems so they have like an elevated ptt a pt an inr they have like an increased d dimer they have like a low fibrinogen and they have like the low platelets and they're really sick and these patients that would be kind of one of the cueing factors for that one for ttp you would also have these patients who have again low platelets they would also have acute renal failure they would also have this actual drop in red blood cells and they would have some type of like fever potentially and neuro deficits so these are something to think about as well and if you do have a high degree of suspicion for ttp sometimes you can confirm that with the atom uh t13 testing and look to see if there's some type of like deficiency there as well hus usually hemolytic uremic syndrome this is more common like your children your younger kind of children but there's some type of like prior like gi infection usually by like what's called the sugar toxin but these people will also have low platelets they'll have some type of acute renal failure and again you'll have evidence of anemia but probably some type of underlying history of gi issues prior to that so think about that and younger children for help syndrome you obviously think about i have to think about like a pregnant woman okay so think about a pregnant woman that's one particular big thing and then if you think about it help syndrome is hemolysis and then they're gonna have low platelets and elevated lft so they'll have low platelets and increase lfts and then again in a pregnant patient so that's another big thing to think about for these types of majors mechanical valve if they have like a mechanical aortic valve this can actually chew up their red blood cells so that's one particular thing to think about now how do i i can obviously think that it's one of these but how do i really kind of get down to business for these because you said zach check a peripheral blood smear and think about the history for these well for the peripheral blood smear for these it's actually relatively helpful so the peripheral blood smear for all of your maha's so we're going to put it right here the peripheral blood smear will show something called schistocytes and these are just like torn up red blood cells sometimes you can see these things called helmet cells as well but i think this is the big big thing here is the schistocytes so if you see a patient has schistocytes torn up ripped up red blood cells think about some type of maha and then look do they have low platelets that also suggest a maha and then you can think about which one it is based upon their history do they have a history of any word like mechanical aortic valve do they have any of these findings of dic do they have any of these findings of ttp do they have any of these findings of hus do they have any of the findings of help syndrome and that will kind of lead you down that road of which type of problem it could be not too bad right all right next one is infectious now infectious is a kind of a super super obvious one with infectious ones you want to think about a patient who is having a super high fever for all of these patients they're probably gonna have some type of high fever maybe like a rash of some kind and this is a really really important one okay for these ones you want to think about malaria okay you want to think about malaria so in this situation obviously in their history they have some type of recent travel to like africa or some some kind of area where there's a high possibility of it's being exposed to malaria and then they come back with a high fever they come back with fatigue they come back with a lot of myalgias and things of that nature when you look at the peripheral blood smear on these patients you'll be able to see the inclusions of the actual malaria inside of them so you'll be able to see the inclusions inside of the red blood cell they get inside of the actual red blood cell and so you'll be able to see that on this one on their blood smear the other one you want to think about is something called babesiosis so it's called babesiosis so usually this is due to a tick bite so if you look in their history and they have some type of tick bite they have like a rash they have high fevers they were in an area like wisconsin or something like that then they could have been had a it could have been a potential babesiosis so in this situation their peripheral blood smear can actually show something that's very patho-mnemonic called a maltese cross so look for this one as a big one for apobisiosis and the last one is called disseminated c diff really really nasty stuff here if someone gets a really really nasty clostridium difficile infection so they have like just rip roaring diarrhea just peeing out their bone hole and that kind of situation they look septic they're really sick high fevers lots of diarrhea then i would actually go ahead and again look at the peripheral blood smear test for c diff obviously and in this situation they have something called ghost cells that pop up for c diff okay but test for c diff obviously you can check the peripheral blood smear look at their history but again i think one of the key things that clues you to think about fevers i mean think about the infectious causes is very high fevers rashes some type of recent travel into areas where there's a high exposure or again potentially like with c diff lots and lots of diarrhea potentially all right so that's how i go about these so real quick again you check for hemolytic labs haptoglobin ldh if it's positive check the dat if that's positive it's autoimmune if it's not then look at your again peripheral blood smearing history and figure out if it's intrinsic or extrinsic from there we've gone through all of our oh and then lastly again if you think that there could be some type of hyperspleenism check the spleen for splenomegaly by doing a splenic ultrasound all right now that we've gone through these let's talk about the last part here that could be a part of these anemias though it's not destruction it's a loss of blood let's talk about that all right so the last thing is we think it's blood loss how do i determine that so first thing i would actually do is i would say okay i know that it's again i have anemia low hemoglobin low hematocrit low red blood cells check my retic index greater than two percent i know it's an increased destruction or loss problem how do i know that it's not actually a destruction problem what did i tell you to first check right away the first thing you check is for hemolysis so if in these patients the first thing you see is there is no evidence of hemolysis so in other words their ldh is normal their haptoglobin is normal you don't have to go down the direction of checking a dat and then looking for any of these intrinsic and extrinsic hemolytic anemias you're done you already know it's not hemolysis i can move on and say that it's likely blood loss plus here's the thing my friends be intelligent if someone is losing blood you can look at their actual physical exam so do they have any signs and symptoms of bleeding do they look pale do they have power do they have dry mucous membranes decreased capillary refill are they having hypotension tachycardia all evidence that they could be losing blood and evidence of bleeding right in front of you you know look at those things but if if you kind of look at this systematically they're negative for hemolysis and they have some types of concerns for bleeding they're on anticoagulants they just had a recent procedure done think about those things and i think the first thing right away what you're probably going to experience a lot of the time in your clinical world especially in the icu in the hospital is you're going to look and you're going to be like oh my gosh this patient is like anemic and they're going to look and it's because they'd be getting blood draws every single day multiple blood draws every day and that's why they're anemic so sometimes if you were to go down the rabbit hole of saying okay i see the patient's anemic i check their hemolytic i check their writic it's greater than two okay then i go ahead and i do the next thing and i check to see what their uh i check their hemolytic labs their negative oh okay potentially from blood draws so could it be from just frequent blood draws that might be their reason especially if they have no obvious other source the other thing is was there any particular surgery so sometimes was there a recent surgical procedure that they lost blood the other thing i think where you lose tons of blood is what we talked about is the git you can lose tons and tons of blood from the git so gi bleeds are sons of guns so look for any evidence of vomiting up of blood right hematemesis look for any bright red blood prorectum or melano dark stools and if you have potential concerns of these then what you can do is you can actually do something for the upper gi you can do like a in an egd and that will be able to tell you if you have some type of like upper gi bleed sometimes they can even do what's called a nasogastric tube and then they can aspirate out some areas from the gastric tube and see if there's any blood in there after you levage it and then aspirate some stuff back but i think the egd is probably going to be the best and if that's positive and you find something within the esophagus or the stomach or proximal part of the duodenum then you're done if it's a lower gi bleed you maybe need like a c scope so maybe you have to do like a colonoscopy and that's going to show you your lower gi bleed or maybe you do a fecal occult blood test and you find that's positive when you test their stool you do like a digital rectal put it on the little thing and it shows up positive for blood that could be a potential problem so these are things to be thinking about now the other thing that i would say is a really big one that i've experienced a lot of the times that can cause just massive blood loss is what's called retroperitoneal bleed so you know there's a little space behind your peritoneum called the retroperitoneum you can lose a lot of blood from it into these areas here especially if you have like any kind of aortic bleed you have a small vessel bleed within the leg you're on anticoagulants so really be on high alert for patients who have what's called a rp bleed and that's a big one and sometimes for this one we do something called a cta of like the abdomen and the pelvis area so you can do a cta of the abdomen and pelvis to look for any kind of bleed in that areas you know what else sometimes if people kind of like hit like an artery in their leg like they fracture a bone or they get some type of procedure you can actually accumulate a lot of blood within the leg too so take a look at their legs do they have any swollen legs or hematomas any visible things there that's also important too but i think that really just gives you the basic idea my friends of how to approach anemia what i want us to do now is put this to practice let's see if you remember this stuff so what we're going to do is we're going to do some case studies and see if you can determine which type of problem it is with this increased destruction category case study nine okay here we go we have a 75 year old male status post mechanical thrombectomy they had a stroke and they had to go in through like the femoral artery to go up and try to pull the clot out of one of the vessels comes back and then has later a hemoglobin of 6.8 so he's anemic what do we have to do check the retic where tick is seven percent it's greater than two percent what does that mean it's not a decreased production problem anymore my friends this is a what it's either an increased destruction or loss what do we have to do to make sure what's either an increased destruction or a loss problem we gotta check for hemolysis how do you check for hemolysis you gotta check your ldh you gotta check your haptoglobin but you can also check your indirect billy they're all normal if those are normal is there likely hemolysis no there's no hemolysis so what is it likely could be a bleed what do we have to look for signs and symptoms of bleeding so they just had a mechanical thrombectomy they have a big fat hematoma on their hip and they're hypotensive they're tachycardic they look pale you send them to get a ct abdomen pelvis because you think they have an rp bleed and there the arrow's pointing at it there's a bunch of blood sitting there after that procedure you confirmed it now what do we know it's an rp bleed that caused their anemia boom straightforward right okay let's move on case study 10. you get a 75 year old male past medical history of cll chronic lymphocytic leukemia presents with the hemoglobin of 8.9 that's anemic what do we got to do check the retic where tick is nine what does that mean it's not a decreased production it's an increased destruction or loss problem how do i determine if it's an increased destruction or an increase in loss hemolytic labs my ldh is high my haptoglobin is low my indirect ability is high that's him that's evidence of homolysis what do i check after hemolysis is present a dat why do i check a dat or a coombs test to see if it's autoimmune that's positive and it's and it's positive for igg and positive for compliments which one is that is that cold or warm that's warm if it's a warm autoimmune hemolytic anemia there's a bunch of different causes behind this but it's likely the cll that's probably the culprit behind that okay we'll go again we'll go into more of the causes and all the the details of that in individual videos on these anemias but for right now that's the basic concept all right good job we're good we're moving along guys all right 75 year old male cough shortness of breath green sputum presents with a hemoglobin of 9.9 he's anemic check the retic six percent is greater than two it's either increased destruction or increased loss what do we do hemolytic labs oh he's got hemolysis what do i do check a dat why do i check at that or combs to see if he's got autoimmune hemolysis it's positive uh that their that actually combs is negative for igg but it's positive for complements in igm so he does have a positive dat but it's only positive for the again complements what was that one that was a cold autoimmune hemolytic anemia and it's likely secondary to mycoplasma pneumonia and again you can confirm that with a pcr and again we'll go into more of the details of these in individual videos but at least you got that it was a cold autoimmune hemolytic anemia all right 12. 11 year old african-american male treated for pneumonia with bactrim decided to eat some fava beans for lunch presents with a hemoglobin a 10.2 he's anemic what do i do check the retic it's four it's greater than two so it's not a decreased production it's an increased destruction or loss what i do check pharmacist there's homolysis what do i do check a data to see if it's autoimmune that's negative it's not autoimmune what do i have to do now look at the peripheral blood smear and take into consideration his history what's suggestive in his history he's african-american he's young and then there was some type of oxidative stress he was exposed to an infection with pneumonia he was exposed to baction which is antibiotic that can cause oxidative stress and fava beans which can kind of cause some problems all right let's look at what's next thing prefer blood smear what i tell you was the big big words to think about bite cells and heinz bodies g6pdh deficiency what do you actually want to check for g6pdh deficiency the enzyme levels but do you check it while they're hemolyzing no you have to check it when they're not hemolyzing so check it again to see if they're when they're not in a hemolytic state to see if it's low what's my likely diagnosis g6pdh deficiency oh man we're going all right next one 12 year old african-american male presents with chest pain uh he's also got painful and pale extremities with hematuria uh hemoglobin 7.2 he's anemic what do i do checker tick oh 7.5 it's greater than two so there's not likely a decreased production it's an increased destruction loss how do i know which one it is check my hemolysis labs oh he's hemolyzing is it autoimmune nope it's likely some type of intrinsic or acquired problem how do i know look at the history and peripheral blood smear history he's young he's african-american he's got chest pain painful pale extremities and hematuria huh could it be like a sickle cell kind of crisis like a vasoclusive crisis it could be how do i kind of add on to that peripheral blood smear what does it look like sickle cells what do i likely have sickle cell anemia how do i confirm it hemoglobin electrophoresis it's positive what's my diagnosis sickle cell anemia 44 year old female with past medical history bud kiari has dark urine in the morning prince of the hemoglobin 10.5 anemia what do we do checker tick it's 2.5 it's high it's greater than two percent is it hemolysis or is it a destruction what i got to do look at my hemolytic labs there's hemolysis is it autoimmune check a dat it's negative look at my peripheral blood smear and consider my history my history they have bud chiari syndrome that's a venus clot within the hepatic veins and they have dark urine in the morning i can look at my peripheral blood smear sometimes it'll show spherocytes but sometimes it's unrevealing oh it's unrevealing i have a suspicion of what peroxism of nocturnal hemoglobin area what do i have to use to confirm flow cytometry it's positive what do i have proximal nocturnal hemoglobin area all right next one 22 year old male with no past medical history that's pertinent for anything presents to the office with the hemoglobin 9.5 okay nothing special but he's anemic what do i do check her tick it's 5.5 increase destruction slash loss how do i know hemolytic labs they're elevated is it autoimmune that's negative not autoimmune what do i think i do prefer blood to me in history history doesn't really suggest anything what is this peripheral blood smear show oh boy these are spherocytes if they're spherocytes what do i obviously want to consider especially with no person with a very significant past medical issue you know venous clots no kind of urinary dark urine in the morning hereditary spherocytosis with hereditary spherocytosis what do i actually have to check osmotic fragility test if i check an osmotic fragility test it's positive what do i have hereditary spherocytosis all right next one 32 year old female no past medical history presents to the office after a trip to africa with high fevers and fatigue hemoglobin of 8.5 all right they got anemia check their tick it's elevated is it increased destruction or loss how do i know check my hemolytic labs they're elevated is it autoimmune check a dat it's negative it's not autoimmune then what do i got to do look at my history and consider my prayer for blood smear history what i what do i see here high fevers and fatigue trip to africa hmm that's interesting look at my peripheral blood smear i see inclusions inside of these and they don't look like a like a cross like a like a maltese cross and i have a trip to africa with high fevers and fatigue i think it's uh malaria this is classic plasmodium falciparum so i got malaria all right next one 29 year old female no past medical issue presents to the office after a hiking trip to wisconsin came back with a rash high fevers and fatigue hemoglobin 9.5 she's anemic check the retic it's elevated if it's elevated i know that it's increased distraction or loss how do i know if it's which one hemolytic labs they're elevated is it autoimmune that's coupons negative therefore i have to look at my peripheral blood smearing history history well i got high fevers i got fatigue i got a rash and i got a trip to wisconsin where there's potentially ticks what do i got to do get a peripheral blood smear look for a maltese cross look at that maltese cross what's that patho demonic for vabesiosis the 65 year old female who's acutely ill has sepsis hemoglobin 6.5 has low platelets or thrombocytopenia you also have other labs like a high ptt a pti and r a d dimer and then they also have a low fibrinogen again what do i always have to check their anemic checkered tick or it takes 10.1 there's an increased destruction or loss how do i know which one hemolytic labs they're elevated is it autoimmune check a dat it's negative look at their peripheral blood smearing history history suggests that they are very ill they have low platelets and they have a very significant kind of coagulopathy here let's check their peripheral blood smear they have shistocytes and helmet cells that's suggestive of a maha a microangiopathic hemolytic anemia do they have a mechanical valve no do they have any kind of recent kind of like diarrhea along with acute renal failure no do are they pregnant no um is there any kind of like coagulopathies present yeah look at all that that's this is likely dic it's unlikely ttp it's unlikely hus it's unlikely help and they don't have a mechanical heart valve that's mentioned here so it's likely dic so it's a maha likely secondary to dic all right 65 year old female past medical history of non-hodgkin's lymphoma presents with abdominal fullness and hemoglobin of 7.7 all right what do we do check our tick 8.1 increase destruction slash loss which one checkimolytic labs the hemolytic labs are high but they're borderline high so they're not crazy high remember what i told you if you have somebody who's hemolyzing they have evidence of hemolysis but it's just barely elevated and they have this abdominal fullness now what do i tell you to potentially consider think about the spleen right maybe but we know we're in the hemolytic area all right so we can continue to move forward it's just it's barely elevated all right what do we always got to do make sure it's not autoimmune check a dat that's negative look at the history and consider your peripheral blood smear if you need one in their history they have non-hodgkin's lymphoma that likes to involve lymphatic tissue one of those lymphatic tissues potentially could be these spleen lymph nodes all that kind of stuff like that right all right so if i have borderline hemolytic labs that's negative and again they don't have like any history to suggest an intrinsic problem like g6pdh or sickle cell or any kind of like membrane problem i don't have any like low platelets or anything concerning for maha i don't have any high fevers what did i tell you was something to think about consider checking that spleen maybe a splenic ultrasound wouldn't be a bad idea but either way we should check a peripheral blood smear right and check their history prefer blood sphere is unrevealing what i tell you to think about at that point in time splenic ultrasound you do a splenic and liver ultrasound you find splenomegaly you think that they have hyperspleenism all right so guys that covers all of these anemia case studies i really hope that this helped i hope it made sense i know it was a ton of information but my goal at the end of this is that you guys would understand this stuff and you would be able to take any question and dissect it with a very straightforward systematic approach to get down to the bare nitty gritty of what is the problem and then what we'll do is over some time as we're going to go over every single type of anemia we have a video on micro acidic macrocytic normal acidic hemolytic and so on and so forth where we'll go into these in more detail but ninjas thank you guys for being so awesome i love you i thank you and as always until next time [Music] you

Channel: Ninja Nerd

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Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science

Id: MRzxsX5YG94

Length: 102min 14sec (6134 seconds)

Published: Tue Apr 19 2022