Hemepath & Hematology Board Review: Peripheral Blood Smears with Dr. Jeanette Ramos

Hi, I'm Dr. Jared Gardener, and I'm here today again with special guest Dr. Jeanette Ramos, who is one of my awesome team path colleagues. Dr. Ramos, as many of you know, joined us here on the channel last year and did an amazing lecture on non-neoplastic lymph nodes and how they stain. And since then, many people have asked for her to come back and teach more heme paths. And as you all know, I know very little about heme paths, and I struggle with it. So I've asked Dr. Ramos to come here today and teach us about peripheral blood smears, and hopefully, I will learn something, and all of you will as well. Dr. Ramos, thank you for joining us.

Thank you for having me. Peripheral smears are sort of near and dear to my heart because when I was a sophomore fellow, this is when I was introduced to the heme world, and it's what I did with my pathology mentor. Actually, when I continued on in years three and four in medical school, I think having a good understanding of peripheral smears is a good backbone for getting into bone marrow aspirates and bone marrow biopsies.

So, before you can actually evaluate the peripheral smear, the first thing you always do, really, with any specimen is check to make sure you have the correct patient name and specimen number, right? And then you have to evaluate that the peripheral smear is satisfactory to review, and we'll talk about that in the next slide. The CBC has a plethora of information, and so knowing what the CBC can tell you can be very helpful in your evaluation.

And that's complete blood count, right?

Right. For anyone. We often forget sometimes and use a lot of abbreviations in medicine and forget at what level people know those abbreviations are. And then importantly, you need to know what the question your clinical colleagues are asking you. And so that's also important for the clinical colleagues to tell us. For example, I had a peripheral smear once that came in with no information, and I went looking into the note, and the question was something I would normally address, which is, "Are there acanthocytes on the peripheral smear?" And so that's important to know. You may not get your question answered. And then you can finally look at your smear under the microscope and write your interpretation.

So, a good peripheral smear has a film or where the film is with the blood, okay? That goes two-thirds or three-fourths down the length of the slide. A smear that is too short, it's going to be problematic because it's going to be too thick. Especially if you're looking at low in the thick part of the smear, you have artifact. So you won't be able to evaluate that. And of course, that's important for myeloma patients. So it's going to be spread just right.

Thickness. And this is how you make sure that that's happened.

Right. Okay. The film should have a slightly rounded edge without being a sharp bullet point. Okay. The lateral edges of the film should be visible, so it shouldn't have run off the slide, but it should go almost the entire width of the slide. And you should have a film that is smooth without interruptions or irregularities. And then this last one is a textbook thing that I really don't know exactly what they're talking about. Kind of put it in here for completeness, which is when you hold the slide up to the light, you should see a rainbow appearance at the feathered edge. And it sounds really pretty, and I wish I really understood what they were saying. But there are many things like this in pathology where things are supposed to look a certain way, and in real life, most of us mere mortals just shake our heads and wonder, "I don't get it. I don't see it."

Right. So these are some examples of not good.

Okay. So the one furthest on the left, as you can see, definitely has an interruption right here. Not quite sure exactly what happened there, but all of that then is it's all the blood's missing there. There's everything there. This one is way too short and not wide enough. And we're not quite sure exactly why that was happening because the tech that was doing this was a really good tech, and she repeated it, and the blood kept doing that plenty of times. So it's also really important to talk to your techs like, "Hey, what happened here?" and see if there's an issue like that. We also had issues where they were having trouble with the smears, and the techs panicked. This blood has just really, really thick. Turned out the patient had hyperviscosity, actually.

Promoted more laboratory workup. And then this is just poor staining.

Yeah. It's a very different color. It's a very different color. I'm not sure what happened in this one, but that's also going to be suboptimal for interpretation.

Great. All right. So your complete blood count. So I do have abbreviations here for a lot of things. So WBC is your total white blood count, and that is simply your total white blood count.

No, no white blood cells.

We have RBC, your red blood cell count is similarly your total red blood cell count. Your hemoglobin is grams of hemoglobin per deciliter, and that's going to be an okay value to have even if you have a hemolytic specimen because the machine actually lyses them together.

Oh, yeah.

Hematocrit, however, you have to have intact red blood cells, and that's the proportional volume of blood occupied by your erythrocytes. Your MCV is your mean red cell volume, or how big your red cells are. So if you know, are they just right? Are they too small? Are they too big? Microcytes or macrocytes? And then your mean cell hemoglobin is an amount of hemoglobin per red blood cell, and a lot of times that's going to correlate with your chromasia. So are these hypochromic red cells, or is there too much white space in your red cells? But there's a problem with MCH because it's, it's the amount of hemoglobin per red blood cell. It doesn't take into consideration if your red cell is small or if it's big. So you have a big red blood cell, you're going to have more hemoglobin in it, and you can get sort of erroneous numbers, which is why you have the mean cell hemoglobin concentration, which then takes into account red cell size.

Okay. So I would say use your MCHC over your MCH.

Okay. When you're evaluating your RDW, or your red cell distribution width, is basically your variation of red cell size. So some people, well, you and I probably have red cells that are about the same size, so your RDW, it's going to be in that normal range. But if you have people who have small ones and really big ones, then you're going to have an elevated RDW. And platelets, your MPV is the equivalent of your MCV for your platelets. So how big are your platelets?

Okay.

And your platelet distribution width is the exact same thing as a red cell distribution width. Like, do you have all small ones? Do you have all big ones, or a range?

All right. Okay, cool. And so the CBC, what type of blood comes in a tube? The tube, as I remember, the color tops change, right? What color top are you supposed to do for CBC, or does it matter?

It's usually a lab in their top.

Okay. Except in certain situations, which we'll talk about.

Okay. And then do you do the same tube of blood that's used for the CBC?

Ideally, the drop or a few drops of that is taken, and the smear is made from that.

Yes. You're using the same sample to run your complete blood count and to make your smear for visual interpretation.

Okay. And lavender is EDTA. EDTA is the chemical in there.

Okay, cool. All right. So I'm a big proponent, as you know from the lymph node lecture, if you just do that and that, you don't know what abnormal is until you know what normal is. So this is a peripheral blood film from a pathology resident who donated her blood to some machine control and then got her own peripheral blood as a thank you.

So this is my peripheral blood.

Oh, and the extra special specimens today. That's it's fun when it's your own sample. Actually, that's how you know you're meant to be a pathologist, right?

It is. And you should have. So these circles are your leukocytes. And I know that this is low power, this is about at 200x, and we'll go higher in just a little bit. But those are your leukocytes, and just giving you a general gestalt of about how much leukocytes are normal at low power.

And leukocytes, fancy name for white blood cell, right?

So if you're, if you're a beginner there, that's it's what we call them. If you look really, really closely, you can see the itty-bitty platelets, which aren't actually cells. They're little fractions of megakaryocyte membrane. Just the tiny specks in the background.

Huh. And I promise you, I will give you higher power in just a second. And then again, a low power, but you'll notice that that red blood cell looks a little bit different than the rest in the background.

Yeah. Looks like a little chunk or something.

It's a little fragment.

Okay. And so I just point that out, and I know I did not have TTP at the time. I didn't have microangiopathic hemolytic anemia. So don't get too terribly upset if you see one or two fragments in your peripheral blood smear. If you start seeing, you know, one or two per high-power field, then you start getting upset and start making phone calls, potentially depending on the clinicals. But that can happen in a normal individual.

Right. Is it just like, maybe procedural or something? Or we don't know?

It could be procedural. Um, I tend to be a hard stick, so I often end up getting butterfly needles, in which case it could be procedural. In real patients that have microangiopathic hemolytic anemia, it could be a like a mechanical heart valve, for instance, or there are other things. Right. I think that it's important in all pathology, right, to know like what abnormal things are, but also when abnormal things don't necessarily mean pathology for the patient. I don't mean the patient's sick. Right. And sometimes that's the hardest job, right? Sorting out what's an artifact versus what's really something we need to worry about.

Absolutely. So here is a higher power of our fine white blood cells, or leukocytes.

Beautiful. These are neutrophils. In the adults, they are the most common leukocyte. They have what I call baby girl pink granules. They're more subtle usually than your eosinophils and your basophils.

So that's this background, this little fine granules here in the cytoplasm?

Right. Yes.

And what power are we on here? Like, what magnification is this?

Under oil. This is at a thousand X.

So that's why you can't, like, when I see these under my microscope, I don't have an oil lens. I look on a 40x, and to me, white blood cells look a little pink, but you definitely can't see those granules. I get, at least my eyes can't.

Or it's different in tissue H&E sections.

Oh, good point. Is on peripheral films, first of all, H&E sections are hematoxylin and eosin, right? Stain, right? Stain. Okay. So they look a little bit different. They look similar, but you'll notice if you go from bone marrow aspirates to your bone marrow biopsy, it's looking at the right to the H&E, you'll see some different color.

Different. Okay, cool. Uh, and they generally have the neutrophils have three to five segments. Okay. If you have neutrophils that have five segments and greater than 5% of your neutrophils, or neutrophils that have more than five segments, those are considered to be hypersegmented. Hypersegmented neutrophils with less than three are considered to be hyposegmented.

Okay. But seeing five in just one cell doesn't necessarily mean there's some problem, right?

No, it's only if it's more than 5% you said of the total, right? And keep in mind, if you look at cytospin slides, that rule goes out the window because cytospin can artificially give you segmentation.

So this is a small mature lymphocyte. The nucleus is about the size of a red blood cell. You have a thin rim of blue cytoplasm. And in the adults, it is the second most common leukocyte. In newborn children, it is the most common.

Mm-hmm. Leukocytes. I didn't know that. And it switches somewhere in the aging process.

This big guy is a monocyte. It has more of a blue-gray cytoplasm. The nucleus can be variably shaped. Sometimes you'll have a nucleus that looks very much band-shaped, and your techs will have a lot of problems with that. So make sure you look at your cytoplasm. It can be very, very helpful.

In a band, is that an immature or a left-shifted neutrophil?

Or now? Yes. No, it's always more complicated than I think. So the technical term for a neutrophil that we see here is segmented neutrophil. The technical term for a band is band neutrophil. So bands are technically also neutrophils. So it is true that if you have increased bands, so quote-unquote, bandemia, that that can be considered to be a left shift.

I don't have a few bands here and there, that's that's fine. When you get back a little bit more mature into the metamyelocytes, if I see even one metamyelocyte, I'm going to say either rare left shift granulocytes are present or something.

The point is, a band neutrophil can look a lot like a monocyte, right?

That's right. And so the main difference between a band neutrophil and a segmented neutrophil is that it, it basically is smooth all the way through. There are no segments.

Okay. And then monocytes often will have vacuoles in the cytoplasm, and that can be a real help. And especially if you have a reactive atypical lymphocyte, which I'll show you later, versus a monocyte. So reactive lymphocytes can sometimes have vacuoles, but most of the time, the vacuoles are very reassuring that you know you're looking at your.

Okay. But the chromatin pattern is how eventually you train your eyes to determine whether it's a reactive lymphocyte or a monocyte.

Eosinophils are my favorite. They're probably the easiest to identify. They have very chunky, hot pink granules. Am I allowed to say that?

I call them Barbie pink.

I think trademark you. I think you could say that. Okay. I call them Barbie pink because if I'm going to age myself now, back when I played with Barbies, everything Barbie owned was like this color pink. Her car, her house, her dresses. And now Barbie is, it's branching out a lot more. But I call this one baby girl pink. You know, this Barbie pink. So the color's a little different, and the granules here are bigger and chunkier than their refractile.

If you're looking under light microscopy?

Yeah. On H&E. I find that really helpful because I feel like the color of neutrophils and eosinophils can be somewhat similar on H&E, at least from low power. And I feel that oftentimes my residents will say, "Oh, I think they're eosinophils," and it's just neutrophils like in a dirt path biopsy. But I find that if I flip my condenser, I can get that refractile look, and you can really see the granules on the eosinophils. But again, I can't on 40x on the neutrophil. And I find that actually helpful in practice in tissue sections to tell apart.

And then this guy here is a basophil. Now, I find basophils to be the most morphologically variable of all the white blood cells circulating because if you look at a basophil cross-eyed, it will degranulate, which is kind of what this one has done. Most of this is degranulated. And I'll show you one later that's not, but you can still see that chunky purple granulation. These are the least common white blood cell. And in fact, it's the only basophil on my entire peripheral smear.

Wow. Which is why that is the example and not a better granulated one.

You have low basophils.

I think it must be something, something serious. I'm just joking.

What, you know what I did? I've always wondered why don't we see basophils in tissue sections? Like, I've never recognized a basophil in skin or anywhere else. Are they there, and they just don't look like it, or do they only stay in the blood and never get out into the tissue? It's not, I don't know. I've always wondered why is this thing that's in our blood never show up, or at least I can never see it.

Well, so we're even in the blood, and I don't think you're really going to pick them up. They may not stain well on H&E, because I've never actually really looked for them.

Oh my gosh. They're not prominent in the bone marrow either.

Okay. Um, and then some people consider basophils and mast cells to be kind of cousins.

That's what I wondered. If they are like mast cells, but we see lots of mast cells in the skin, way more than you would see in the blood. So, um, some people don't consider them to be related. It's, it's sort of up in the air. They're not the same cell.

They are different. We are different cells. They look pretty similar. They have that clumpy purple granulation. Basophils should have this sort of bi-lobed appearance. So you can see there's. And mast cells don't have that. And mast cells, normal mast cells should have a central pale nucleus that you can barely see because it has so many granules.

Okay. That's cool. That's good to know. I, the only time I really see basophils probably is in CML.

And this is a picture to highlight the red blood cells. The red blood cell in three dimensions is a biconcave disk, which basically means that it comes together in the middle. So it's fatter on the outside and thinner on the inside.

Which makes it look like a doughnut.

Yeah. On the, so there you go. You now have your first pathology food analogy for this session. And it should be about a third. If you have an increased, you know, pallor, that would be sort of your likelihood.

Should I look for iron deficiency?

Clear. The clear part in the middle, you're saying, should be about a third of the space across the whole red cell, right?

Okay. And that clear part is not really a hole, right? It's, it's really connected. It's just that the section we're seeing it looks like a dip.

Right. It's not really an empty space. So I mean, dip, right? It's a dip.

Okay. It's important to have that so you're, you're ready. Let's, I can fit through like all the capillaries.

Cool. And there are platelets that you can actually see. There is a little bitty platelet aggregate there, and you know, individual platelets here. Little bitty aggregates like this, if they're few and far between, I don't really mention them because it's not really going to affect the platelet count. But larger ones will, and we'll talk about that a little bit later.

Okay. But now you can see them. They're granular. And if you look at the megakaryocytes, it looks like megakaryocyte granules. And in the bigger megakaryocytes, I feel like those granules sort of look like the texture of a furry purple Muppet. And it's so your platelets should look a little bit furry.

All right. So this is now our first non-normal example. I would not be feeling very well if this is me. So first of all, look at about the whitespace you see in my peripheral smear, and I run with a hemoglobin around 14.

Give me the whitespace between red cells. Between red cells.

So a lot lower here. This, oh, they're really, really spaced out. And you'll notice that there are some red blood cells that have that donut-like appearance, but there are some that have lost their central pallor completely.

Yeah. You're surrounding some of them.

So this hemoglobin is 7.7.

Whoa. And what's the, what's the lower end of the normal range?

Well, that depends. Okay. It depends if you're, what age you are.

Mm-hmm. And it depends if you're male or female.

Okay. Uh, so the lower end of normal for an adult male is, and it depends from lab to lab, too, right?

12-ish. Yep.

The male hemoglobin is about a gram higher than female.

Okay. And so, yeah, so 7.7 is going to be low. It's not quite a transfusion low yet. That's usually below 7, or if you have like coronary artery disease and are symptomatic.

Now, I'm going to give you. So, so all the black arrows are pointing to those cells that I described that have lost their central pallor, and those are spherocytes.

Okay. Cool. And the blue one, if you look really, really closely, you can see some fine basophilic stippling, which is why it got its little special color. So this patient doesn't have a history of hereditary spherocytosis.

No, she did. I would expect pretty much all of them to look like spherocytes. So this is probably going to be an autoimmune type hemolysis. And I mean, that's probably what this is.

And is that like, you get antibodies attached to the erythrocytes, the red blood cells, and then the spleen pulls off little bits of membrane, and it makes them lose membranes, so they turn instead of a biconcave disk into a sphere?

Right. Because, thank you. Remember this for me in school. It's the fluid kind of stays about the same, and you're taking away membrane, so then it turns them into spheres, and then they can't bend through the capillaries, so they great, you can rupture. And like, so don't.

And then you don't have functioning red cells.

Okay. So in hereditary spherocytosis, where all the red blood cells are spheres, a lot of patients end up getting splenectomies to help to avoid that problem.

Okay. And their spleens get rather large trying to take out all the spherocytes.

Oh, okay. They have hereditary spherocytosis, it's a chronic hereditary or a chronic hemolytic condition. And so you're gonna still get hemolysis as you're not taking out all your capillaries. I mean, you need those.

Mm-hmm. But at least your spleen isn't like holding on to them anymore.

Yeah. And I always have problems remembering like which mutation is more common in hereditary spherocytosis or elliptocytosis, and it's ankyrin for spherocytosis and it's spectrin for elliptocytosis. So the S don't stay together.

Yeah. I always have to use unusual tricks like that to help me remember things. I get confused a lot. And or look that up five minutes before you take the test.

Yeah. That's what I do with the coagulation cascade and complement. I can't ever remember it. I have to look at it before every exam. I can never get the stick.

So for this, you'd probably check a DAT.

A DAT is like, it's a Coombs test, right? Basically. So it's checking to see if there's antibodies on the red cells, right?

Okay, cool. This was a very interesting case that we had. So you'll notice that there are red cells and a few platelets, but like no white cells in this picture at all.

Yeah. Turns out this patient actually came to us for thrombocytopenia, and she was almost 70 years old, had no real medical history of anything, no history of anemia, no nothing. And it turns out her pancytopenia spontaneously resolved. So it was probably actually a viral insult. But interesting, prompted this workup for MDS, and it turns out she actually had all her life hereditary elliptocytosis and never knew.

And never knew. So unlike hereditary spherocytosis, where you have all these problems with hemolysis, you don't generally get that with hereditary elliptocytosis. So you could have it your whole life and be asymptomatic, basically, until someone happens to look at your blood and say, "Oh, look, they're all ovals." And that happens often. Now, I'm not saying that happens all the time, because some patients do have problems with hemolysis, but a lot of times it presents sort of like this.

And then the black arrow is pointing not at an elliptocyte, which are these guys here, those are elliptocytes.

Okay. But what's that big guy?

Exactly. Uh, it's also called a burr cell, or an echinocyte.

Yeah. Like a hedgehog.

Yes. Was that on the last slide too? The glass? I thought I saw spike.

You saw one of the same. And I'll tell you why, because often when we get these slides prepared for our study sets, they have sat for a few hours. And it kind of, the shape changes as the red cells sit. And or other processes such as uremia. And this patient did not have uremia.

So sometimes they're real, and sometimes they're artifact. But they, you have to look at the whole clinical picture to see which makes sense. When I'm seeing a lot of echinocytes, I always check the chemistry. If the BUN and creatinine is high, then I will specifically comment on them. If I know that this is an add-on order and the BUN and creatinine that's normal, I may or may not comment on them depending on how.

So I'm just going to interject here. This is an awesome example of how pathology, although we do a lot of looking at pictures and images and microscopic findings, we're doctors. We have to put together the whole picture, the clinical, the other lab work, see if what we're seeing makes sense, and interpret it with that lens. Right? We're not just like saying, "Oh, here's the findings. Good luck to our clinical team." We work with them, and with all of the aspects of what the patient has to try to figure out what makes the most sense of what's going on. Right? And that kind of problem-solving, some days it's maddening because it's hard, but it also is cool when you find a find an answer that makes sense and you can actually make a difference for a patient.

Eye. Those are the moments I really like, at least. So some of the times you get the most words from me when I have absolutely no clinical history.

I think yes, me too. Because I don't know what's going on. So you get a lot of like, "It could be all of this umbrella thing. I don't know anything." So you're going to have to go back to the patient and figure out.

So dear clinical colleagues who are watching this, please help your pathologists out. Help us help you. Tell us clinical information about the patient because we're able to often give you more information back when we know more about what's going on. And that's, that's everyone wins, right?

I think Howard, and I'm sure you have to bias where the clinical colleagues think they're going to to bias on and what we're going to say if they give us pertinent information. And that's really not true. We're better able to help if we have one.

And we're trained to work around that, right? I actually try to look at slides first without seeing, see what I, what I see, and without knowing any clinical. Then I look at the clinical afterwards and see, does it make sense what I saw microscopically and then what the clinical situation is? And if it does, that's great. If it doesn't, then I go and rethink the situation. So it's good.

So what do you think of those red blood cells?

Mm, they are strange shapes. Like this little one looks like a mouse or something. These little ears, this little tail, tiny little foot. Maybe I've been looking at slides too long.

I mean, those are normal-ish. I think this is like, you know, that's like Italy or something. I don't know. They're very irregularly shaped. And then these are platelets, right?

Are they bigger than usual, or is that okay?

They're slightly bigger than usual, but in order to call a giant platelet, it has to be the size of a red cell. So I will point out that there are some elliptocytes and acanthocytes on the slide. And this is actually a patient who had a history of hereditary elliptocytosis that developed hereditary pyropoikilocytosis after his he got a transplant.

Hi. Hero point. Poikilocytosis. Pyro like the flame. Okay. So the red cells become stable at higher temperatures. Oh, pregnant. So you will see also some spherocytes here. Yeah. And it's actually the opposite of what really happens with pyropoikilocytosis because normally you have pyropoikilocytosis in the pediatric population, and they will sometimes burrow out of it into hereditary elliptocytosis.

Huh. And he eventually cleared this again, but it was sort of a clinical picture. Gets to like how, and I think that they call it that because it almost resembles this picture. They're not quite as funny looking. But this is what you see in a burn patient.

Oh. But these are very, very, very small microcytes. And they're not, these are the spherocytes. See how they have no central pallor and they're darker color? I think the hemoglobin's all bunched up together, I guess. And see if the central pallor remains here. So they're not microspherocytes, they're just really, really small microcytes.

Huh. That is one of those, like, they put this picture up and they would expect you to know that this is a burn picture.

Burn patient. So those are microcytes. Micro, like micro, microcytes. I cannot even like iron deficiency, microcytosis, microcytes. They're small, little, little tiny donuts. And then also having a spherocyte. Does that go along with burn?

Yes. Okay. Interesting. So I'd expect the RDW on this patient to be quite high because you've got tiny and big and everything in between.

Right. Range. Okay. Although these little tiny ones may get counted as platelets because there's no small blood cells. So you might have to adjust your platelet count.

This is a different red blood cell morphology. Some of those look kind of like echinocytes to me. Like they're.

Well, these are. Okay. Those are. These are. Thank you guys. I like those. And again, this is because I definitely went back to my techs and said, "Please make me a slide for my daddy." Said, "Oh." And I have been sitting. I see like I've been sitting. But these are where your eyes should go.

So these are called blister cells. Obviously, they've got like a little bleb, a little blob that's clear, coming out at the end.

Okay, cool. And does blister cell dredge up anything from the recesses up here?

It should, because I just retweeted something just the other day that someone posted of a smear with little blister cells, and they said it was due to exposure to something. But I can't, I guess I didn't pay enough attention when I retweeted it because it didn't stick in my memory. But they, I thought those are cool-looking. I can't remember what it is.

They're not specific for, because it can be seen in other things, but you really should check your patient for G6PD deficiency.

Oh, okay. Which is what this is. Okay. G6PD deficiency. And then you also have this little blue dots there. Okay. And you can also see that this red cell is a little bit more purple on its neighbors, and that's what we mean when we say polychromasia.

Oh. Now, if you stained it with a supravital stain, a special stain, you could call it a reticulocyte, but you can't unless you do that special stain.

Okay. So we say polychromasia. So it's sort of a synonym for, we can't call it a reticulocyte, but that's pretty much it.

So this is a patient that has iron deficiency. It's not the best iron deficiency slide because I'd really like to have more of these target cells or codocytes. But what you can see is that they're smaller than what we've been seeing, and that's more like two-thirds of the middle and one-third of the actual donut hole in the donut is bigger than it should be, right? And the hemoglobin is smaller.

Okay. And so unless you're on a diet, you'd be really upset if you got that. Some of the other ones, and there's more white space between the red cells here, right?

Brush tells us there's fewer red cells.

All right. So this is iron deficiency anemia, right?

Tom. And your big sort of differential diagnosis is going to be your thalassemias. And so there's this thing called the Mentzer index that you can do. I don't tend to use that as much. It's a division of the MCV by the red blood cell count.

Okay. I tend to look at more of the, are my rule of threes being obeyed or not? So in iron deficiency, your rule of threes are obeyed, and you're going to ask me now, what is your rule?

Yeah, I was just going to say, did you say that because I forgot.

Rule of threes. So the hemoglobin should be about three times your white blood cell count, and your hematocrit should be three times your hemoglobin.

That sounds pretty pretty cool.

It is. I don't know if I ever knew that, but if I did, I've forgotten it. And so in iron deficiency, you should expect a drop in your red cell count along with your hemoglobin. Adequate. And oftentimes in thalassemia, you actually have a normal to increased red blood cell count.

So I use that. And on tests, on tests, your RDW is going to be very helpful because you would expect to have an increased RDW in iron deficiency and a more normal RDW in thalassemia. In real life, throw that out the window. Because yes, you often do have an increased RDW in iron deficiency, but I've also not uncommonly seen increased RDWs in thalassemia patients. And then you also get into, well, thalassemic patients can also get iron deficiency.

Oh, you could have both. You can have both. So you just want to be careful. Okay. So this is actually a thalassemia, and it's not alpha or beta. This is actually Lepore Baltimore, which is a delta-delta beta thalassemia. Uh, it looks the same. It's so microcytic. You have a lot of these target cells. The other name for target cell is codocyte. Don't miss a test question because you don't know the other name.

Yeah. Always know the variable variant names for things, right? And target cell, for whatever reason, is double target. Has a double target.

Yeah. So if you think about like structurally what is happening there, in order to see a target cell, instead of your have like a bowl and you're in the middle of your biconcave disk to be able to see that.

Mm-hmm. And a lot of, a lot of target cells, but you often see a lot of target cells in iron deficiency. So both thalassemia and iron deficiency can have it.

Okay. It's not going to, not going to really help. But if you've been treating a patient with iron deficiency, or your iron panel comes back as not iron deficiency, and they've had persistent microcytic hypochromic anemia for their entire lifetime, you really should be thinking about thalassemia or something along that lines. If they've had a history of normal, like normal, you know, hemoglobin, all those values, then that's probably something acquired versus.

Oh, if it's been normal before and yeah, that doesn't make sense because thalassemias are like genetically inherited, right? And they're hemoglobinopathies. So if something's wrong with the hemoglobin. So I consider hemoglobinopathies to be sort of structural aberrations that cause misfolding, and thalassemias to be quantitative.

Oh, okay. So when you have an alpha thalassemia, you're missing alpha chain. When you have a beta thalassemia, you're missing beta chain. Or it's a little bit weird because it's not that you're sort of missing your beta chain, it's that your beta chain and your delta chain are like one chain because of how the mutation happened.

Then to test for thalassemia, you do hemoglobin electrophoresis, though is that one of the ways?

You know, okay. Okay. So sorry, I'm leading you way off the path.

That's okay. I like this. So hemoglobin electrophoresis can be helpful for beta thalassemia trait, okay, if you don't have concomitant iron deficiency. Okay. If you have iron deficiency, it will artificially decrease your hemoglobin A2. And in beta thalassemia trait, what you're looking for is an elevated hemoglobin A2. So if you have both of them together, you might have a normal hemoglobin A2 and you might miss it, which is why we say you can't really do hemoglobin electrophoresis for this if the patient is iron deficient. Treat the iron deficiency first and then come back.

This sounds like a whole entire topic for us for another video. So alpha-thalassemia, what you're looking for would be like hemoglobin H inclusions. And with some of the newer techniques, yeah, you can maybe pick those up, but at least on the gel, they would run rough.

Right off the gel. Okay. So honestly, your better test for alpha-thalassemia is going to be molecular PCR.

Okay. No, wait. Is this a hypersegmented neutrophil?

It's way hypersegmented. It's got like, what, ten? One, two, three, four, five, six, seven, eight, nine, nine, maybe something. A lot. Some, a lot more than five. Very much more than five. And I will tell you that the MCV on this patient was quite high, probably about 112, and it really should be under 100. So this is a macrocytic anemia to contrast with your microcytic.

Okay. And we have target. Are these target cells here?

That you're still targets here, right? Right. So also, the point of target cells are not really specific to you anyway. You can also see it in liver problems.

Okay. Which he might may or may not have had. So hypersegmented neutrophil and then a macrocytic anemia, I want to say, is this B12 deficiency that gives you that?

It can, but that's not it. Oh, this is folate deficiency.

Folate. That's right. I knew there was something else too, but I couldn't.

So in the grand scheme of things, which is more common, folate deficiency or vitamin B12 deficiency?

I think folate.

Folate. Why? Because B12, our, I seem to remember that B12 stays around for a while and it just got a longer half-life.

Yeah. So you got to really be, you got to be like hardcore vegan or something, right? And like not eating, no offense to any vegans watching, but if you're not eating any meat products, it's nowhere yet B12.

Something like that. Something like that. And I, I know there are a lot of vegans who are very educated and know how to supplement correctly.

Um, but is, so yeah, most, because I know, know a lot more about food than I do, probably.

Oh, absolutely. Uh, so yeah, so this is folate deficiency.

Folate deficiency. Mm-hmm. Oh, is this the nucleus retained?

How old? No, clearly not. How old are you? So weird. That's not what this is. That's just a frank red cell.

So are you typical because it's not nice and round? It's good. Yeah, like a little blob coming off to the side here, right?

Yeah. It almost looks like one of the Star Wars ships. It also has a little bit of basophilic stippling.

Okay. That red cell shape, kind of a teardrop or pear shape, maybe?

Teardrop. Right. You're just the other name for it is either dacrocyte or dacryocyte. Or the Y is sort of optional. I like the Y and I make them learn it every time I do a case because it has the word cry in it. And they're dropping, crying, Jack, cryocyte, dacryocyte. That's nice. I like it.

And then there's some that is poikilo. So they're a little more bluish purple, right? As opposed to the red of the other red cells.

So the dacryocytes, what you'd be wondering about is, is there an infiltrative or fibrotic process in the bone marrow?

So they're like getting squeezed out of the bone marrow, and that's the way I, in my mind, visualize it. But I've always been told is that, yeah, it's sort of like it squeezes out and so then you have the pinpoint at the like last part.

Uh-huh. I'm not sure even if it's not true, it's a nice story to tell ourselves to remember, right?

Exactly. Oh, and those are sickles, right?

Right. And how do those differ from the tear drop cells themselves?

I'd say pointy on both ends. Exactly. And that's the technical definition is that the dacryocyte, as I explained, did on one end, bulbous on the other. And the sickle is pointed on both ends.

Okay, cool. And so this is sickle cell anemia. And look who's here. Targets again.

Huh? Targets again. All right. Hmm. No, this is the purple. You've got two arrows. The blue arrow is hemoglobin bodies.

Hemoglobin. Which are iron. That's iron. Okay. And then those are your Howell-Jolly bodies. See how they did dark purple, little.

Yeah. Their little nuclear remnants. So they're nucleated. The nuclear red cell left a little piece of itself.

Okay. And you often see those in patients that have splenectomy. Now, in your sickle patient, sickle adult patients, almost all of them have either had either surgical splenectomy, or they've had a lot of infarcts and sort of given themselves an autoinfarct, and you'll see these findings. And you can see that there are sickles here.

This right there. Yeah. And then what about that arrow?

I assume that looks like a platelet sitting on top of a red cell, but maybe not. There's a little circle around it, like a little halo.

And that's exactly right. So this is a trap. There are often test questions of what is this, and they'll give you Howell-Jolly body, hemoglobin body, microorganisms. And this is just an overlying platelet because it's got that same kind of furry look, right? As they're kind of like blue and purple together.

But wait, now this up here, is that, maybe Howell-Jolly, or maybe not?

Yeah, that's probably a Howell-Jolly body.

Consists. Is this also a sickle?

Right. Okay. Okay, cool. And target cells.

The black arrow looks like a sickle again. And the blue, I thought maybe it was, I couldn't tell if it was like a blister there, but it doesn't look quite like those other blisters you showed. Kind of this one's kind of irregular shaped. I'm not sure what those are.

So those are either called SC crystals or SC cells. So this patient has hemoglobin SC disease instead of hemoglobin SS sickle cell disease. So it's a combination of hemoglobin C and hemoglobin S together. And hemoglobin SC makes these irregular crystals.

Now, I don't have a picture of hemoglobin C unfortunately, but hemoglobin C has nice pretty tetragonal crystals. And that you should Google and look at because that is also those pictures that they put on and expect you to know the diagnosis.

So there's crystal inside the cell, and that's what's making the cell distort its shape.

Yeah. It distorts. And and again, in hemoglobin C, it's a nice crystal. And people that have patients that have SC, they still look at some sickle cells as well, right? But not normally as many.

You're normally hunting for them. They can still get sickle crises.

Okay. And then this is a platelet on top of a red cell, right?

Yes. Another trick.

Another trick. Hmm. Little blobs or fragments. Red cell. And what's the other name for fragment?

I just said it. Yes. Of course. Yes. It's just a schistocyte. It's just the center. The true fragment.

So you know this patient also has a spleen because there's a Howell-Jolly body. And is this polychromasia?

Slightly bluish.

Slowly learning. Which you honestly expect to sort of see in splenectomy patients because the spleen isn't like taking out as much and wasn't taking out anything because it's not. The spleen actually is a very highly functional. So it's splenectomy. I expect to see some target cells. I probably will expect to see some crenated red cells. If this patient is at all stressed, I expect to see that Howell-Jolly body. This patient also has at least three fragments in a high-power field. So those are the ones where you're like thinking, "Oh, I need to start counting high-power field fragments."

So this means that the cells are being sheared and torn apart within the blood system somewhere, right? And within circulation. So. And so this is either your microangiopathic hemolytic anemia, it might just be the spleen is it clearing about?

Oh, okay. Because, you know, I have a spleen and I have some fragments, and the spleen will mop up. So we all have some breakdown of our red cells, but normally they just get taken out by the spleen. But if you have little clots or something, like in microangiopathic hemolytic anemia, then that causes the red cells to tear apart in circulation, I guess. Or a mechanical heart valve.

DIC. Any of those sort of circumstances. So now I'm counting. Now, often in your true microangiopathic hemolytic anemia, you're like.

10 or more Brad carbon. Is it's not subtle, okay? However, there are cases that have none. You have true human look anemia, and you don't have serious items, just slides. And I can't really tell you why this is. A time where chemistry would help, though, because if you have a hemolytic anemia, your bilirubin won't go up, right? Okay. So happy Blauman is something that I use, 'cause LDH isn't will also go up. Oh, right. It's specific to red cells. Any license, a light release LDH. Uh, so if you have a decrease haptoglobin and you have increased bilirubin, you have an increased LDH. Like, all that goes together with, "Oh, we have hemolysis somewhere." But sometimes the premier will look red cell morphology normal. Huh? You don't really know why. Interesting. Those are frustrating. It's your pathologist gets really frustrated when they can't put the puzzle together. Yeah, when things don't work the way they're supposed to. You're putting together a puzzle and like the last piece is a whole because they didn't give it to you. And I bought all right. So they, the red cells seem to clump together there a little bit. I don't know if that means that they're like almost molding, but I don't know if that's real or an artifact. So that's real. Okay. That's why it takes the pig. And there seemed like there are more platelets than the other ones we saw, but I don't know if that means anything or not. I think that's probably more normal, and the other ones were probably low. Okay. Uh, so these are cold agglutinins because the red cells are gluten aiding. And that your lab or my lab has a warning procedure that they will use. A little gave me this slide pre-warmed, and they'll give me a slide who swarmed. And you would expect to see the agglutination valve and or mostly resolved with the one specimen. And then you feel pretty good about this is probably cold. And what does it mean? I, it's it's a, I remember learning this in blood banking, but it's been so long. It's antibody mediated, okay? And when you get cold, it's supposed to hold it. Occlude nates, okay? Like that. Interesting. Yeah, it honey does weird days. Hmm.

So now we're not looking at red cells, we're looking at the leukocytes, white cells. All right. So I see granules there. I can't tell if it's by lobe. They're like kind of a U-shape. So that's probably more of a band. A band. So that would be that would be what a band would look like. We talked about it, okay, earlier. And I said, imagine that the segments are gone. So the segments are gone. That's that's a bit. So hypo segmented neutrophil, basically. No, that's totally different. Is it really? Yeah. Oh, yeah. I'm glad I asked that. Hypo segmented, and I'll show you a picture in just a little bit, means that there are literally less than the normal number of segments. This is just a little bit younger and has a second. Oh, okay. I see. They mean totally different things. Okay. So this is a man neutrophil, but do you see how it's not quite that same sandy baby girl pee? Yeah, I felt like the granules are a little different color and a little bit slightly bigger. Yeah, not as fine. Right. So this is called toxic granulation. Oh, and this happens to be growth factor induced. Oh, but it could look the same with substance. So like maybe a growth factor me like someone's had a transplant, marrow transplant, or something, and they're giving them growth factor to regrow it. Means that the white count is low. Oh, can either be B or they're getting an auto transplant, and they are harvesting CD34 positive cells. So they've given it. So they've given them a stimulus, whether they're granulocytes. Um, sometimes in MDS, you get given it. Sometimes after chemo, they'll need a little boost with especially if you end up with like a neutropenic sort of sites back with the marrow is being stimulated to produce to produce more neutrophils, basically, right? And that's so that's either and dodges your body's making it because well, or you're getting a medic. Yes, this is medication. Medication cost. Oh, yeah. This is the growth factor of the medication. Okay. Cop sepsis can also look like this, like you're, you know, your body is route dot fighting, usually, you know, bacteria. So it's sort of a reactive change. So this here is your hypo segment. Oh, so it still has a segment. It's just like two letters, two of them, right? Okay. Right. We'll talk about that a little bit. Start here. So this is hypo granular. So instead of having that prominent regulation that we saw, this is just all of them. And that's a disparate feature. And despotic means like potentially myelodysplastic syndrome. I mean, not necessarily, but but that's one time where you could get dispo esis. It's it just means that it's it's an abnormality. Okay. And so it's not wait, it's telling the right thing. Just plastic. Uh-huh. I see. Just poetic meaning that there is a problem in the formation of this. Okay. Okay. So poesis granule. Oh, police and spans, you know, the formations granulocytes richness, the maturation of Richboro, and so displaces means it's not forming the right way. It's not forming the right. Okay. So this is also hypo granular, but is hypo segmented. Uh, that's a pseudo Pilger Hewett. So, oh, I remember hearing about that a long time ago. Right. So this is important for sort of like test purposes. So culture Hewett anomaly is supposedly the most common like neutrophil anomaly. I've never seen it ever. I've never seen real Pelzer Hewett disease. There are two types of paltry Kiewit disease. There's heterozygous, which is a lot more common, which I've also never seen. And homozygous, which I expect to never see. Uh, heterozygous Eldred anomaly has neutrophils with two segments. Homozygous will have one. Okay. Heterozygous, you're pretty much normal except that you don't have any symptoms. Basically Trump, not really. If you're homozygous, though, you do have like some bone abnormalities and other sequelae that come along with me. Okay. But honestly, I feel like you have to be really, really unlucky because again, I've never seen it. So having two parents, perhaps? Yeah. So homozygous, you have two carriers have a baby, right? Around twenty the Cho, both get the bad gene, the gene, yeah, right. And it will have one. And so what you'll what you'll have to really watch is that you don't milah sites, 'cause they'll have to whine nucleoside look like. Okay. Great. Um, so on test questions, a lot of the time they'll give you percentages of the cells that are high post segmented. So in true culture with anomaly, you would expect like most of them to have it. So really, you should be looking for greater than 50% and really greater than 80% of them should be hypo segmenting. Okay. If you have like 20%, 10% of them, that's probably MDS or some sort of chemotherapy type artifact. And MDS is Milo's plastic syndrome. Focus. Hmm.

Well, there's a blue, a pretty blue color blob in that. I think that's a neutrophil. It's got kind of funny shaped segments, but I don't know what it means. And this is a celebration picture. So, um, not the same patient, but a similar patient. Almost like a crystal or something ionic. It's, I don't know, kind of jagged up the edges. That blue, I don't know. I give up. So you've probably never heard of these. Oh, okay. No, that's good. Um, I kind of honestly prefer the Wikipedia term for this, which is critical green granules, but we sort of colloquially call them the like green granules of death. Green granules of death. That sounds very ominous. See them in patients who are who may die very soon after seeing this. And a lot of them have liver failure. Oh, stop saying all of them die after finding this, but it's recommended that you call your clinician when you see this. So it's serious. This is a serious, ominous like almond is finding that the bone marrow is stressed because that's a more normal nucleated red cell. See how it's okay? So it got out of the marrow too soon, right? Before losing it, right? So I would say that if you have nucleated reg, really look for polychromasia because polychromasia is your first left shift stage. Completed red is like your next. Okay, that's like, I am really stressed and now I am letting of my nucleated res because I just need to get red cells out. I don't need them to mature anymore. Huh? And I want to compare those those green granules to that inclusion, which is a doli body. Yeah, you can do it. This is a lot of painter and smaller. All right. And sometimes it can be a little bit more prominent, but it's also more blue. And those are the other ones are supposed to be more blue-green. And honestly, it's probably gonna be a little bit stain dependent, but these are much, much more common. You would expect to see a little bit of toxin granulation. This is actually the same patient from the band that we saw before. Oh, okay. I'm looking for doli bodies. Um, and then this is an infant whose mother had this known anomaly. It probably also inherited it from her. Hmm. Well, I thought that thing was a big platelet. If it's, oh, okay. But I don't know what the in the middle is. Is it a neutrophil? It's got like will fine granules, but it seems that the nucleus looks very strange. I don't know what to let's make it that. Just squint a little bit here. Oh, there is a blue blob there. Yeah, there's a little blue triangle. It's called that a doli, the body like inclusions. Only body like conclusions. They're ultra structurally not the same thing. All their bodies are rough particular. Okay. And they're not exactly the same thing, but they look they look alike on that smear. Okay. So this is an autosomal dominant inherited anomaly. It's very heavily board tested. And this is May to hey, hey, and that you get a giant platelets, right? And then yes, little inclusions. Okay. Yeah. And is I mean, this technically isn't quite giant. Oh, yeah. This is still smaller than a red cell. What I mean, that's that's internal. Yeah. And so, you know, common things being common in a in a parent that has this known anomaly and a now infant that has his peripheral smear, this is most likely going to be made headway. Okay. It's 50% chance he was going, or she was going to get. Mm-hmm. I, I'm afraid to say it, but those remind me of is it downy cells in or Epstein-Barr virus? Something. I don't know. It's calling the mite. Several neurons are firing, but they don't know what they're saying. So I probably better be quiet. I'm just letting you tell me virus. All right. So think about the way it merges with its neighbors. Makes me think of that, but I don't know if that's really what what it'd be excited. Just so you kind of got lucky and you picked the exact right virus. So again, this clinical scenario is going to be important. So if you have the, you know, the bilateral is not, but they all of that in a teenager, young adult, or you know, so mono, right? Yeah, infectious mononucleosis. Not to be confused with monocytes. All right. Yeah. Um, but any virus can look like that. Any virus can. And and this is a lymphocyte. These are lymphocytes. They are reactive lymphocytes. They are probably T cells, okay? So their nucleus looks a little different. They look bigger and more irregular, kind of shape and way more size. Right? Right. Yeah. These these are like fully functioning, not quiet. Okay. And you'll notice that it gives way to red blood cells here. It's a little bit bluer where it's hitting the red cells, kind of squishes around them. Huh? Right. I'm some people call that Dutch skirting. So I googled Dutch hurts and I don't know what they're talking about. Um, because I don't see anything that remotely looks like any of that. But they call it Dutch skirting. And when I see that, honestly, I'm a little relieved because blasts tend to be bullies and push red cells out of the way. And your reactive lymphocytes are like, yeah, man, I'm busy doing stuff. So just kind of oozing around. Okay. So but otherwise, these could get confused with blasts, right? Necessary. If you don't know this, this particular one, probably not. The chromatin is a little bit too mature, but I mean, it's activated. And the chromatin starts to get a little bit more open. So then she can get prominent nucleoli. It's really sort of frightening sometimes. They're often what we call these like plaza missus. I enjoyed like dark blue ones that are also. And what do you call? What is the work that a word for? No, you're right. They're Downey. So Downey said, okay, there's there's like Downey one, two, and three. And I don't remember which one of the Roman numerals is, but yes, you're right. They're called Downey cells. Cool. Mm-hmm.

I can't tell if that's a neutrophil. Maybe that has three lobes. And then there's a little blob like his little signet ring looking thing there, or if it's a yo. I'm not sure what what it is. That's a nucleated red cell, right? Yes. Okay. I got one thing right. And the yellow one. Oh, yeah, 'cause it's kind of a bluish color, right? And it's overlapping with another one here. I wondered why I was. But there's just sitting on top of you. So we're in a thick portion of this. Oh, yeah. Those cells are stacked up, kind of huh? I don't know what is what is that? It looks like something I should know. That's fungus. Fungus. Well, it looks a lot different than is it like histo or something? 'Cause if it's that small, then histo is one of the only things I would think of. Histoplasma. So I don't I don't specie ate. Well, sure. Ever on anything. I will, however, in the area I live, knowing what is available, when I've talked to clinicians, I will tell them, I can't say based on morphology, but my gut reaction has said it's probably histo until proven otherwise. But you need to do all the appropriate. Yes. Yeah, I mean, you can send blood cultures for sure. Fungal cultures take two weeks. And you can't let a person with like that, 'cause this is gonna be in the marrow. Yeah, if it's in, right? If it's not in the peripheral blood, then surely the marrow. Yeah, because when we see Histoplasma sindorim path, oftentimes it's a widespread. The patient has either HIV or some other immune suppressed status or transplant patient. So it's all over the place, right? So so they need to treat appropriately. So that's not something I'll put in my definitive report. It's just sort of you say fungal yeast and inside intracellular yeast. Mm-hmm. Present. Cool. That's really fascinating. Uh, now keep in mind that you see the carnation here. So this sat a little while. I got I think so. Some of this cremation is also artifact. Hmm. Yeah, I see the blue and then I see that bright magenta color there. And then same thing here. I see magenta and then blue around that. I don't I don't know what to make of that. I, what is this? This is podium by that. Oh, wow. And so this is the gametophyte. Okay. And that's the ring. Oh, the ring. Oh, and right. Yeah. So you're saying it's a little created because it's that it's one of those like how we have malaria and begginers can't quite be choosers type of a deal. But it's it's so-so malaria. All right. I often don't get to see the gametophyte. So that that's not a platelet. That's the community. Yeah, that's why I always like that. That doesn't ring any bells for me. And now that you say that on the ring, I know this is vivax because the PCR came back is 5x. I also knew the travel history and it was 95% 5x in the range in a day went right. Uh, but I will say that your collisions do not really care. What they care about is is this falciparum? So 'cause that's the really bad one, right? Bad malaria. And this is not something really as a matter of pathologist, you should be like, oh, I'm going. That you probably should get your microbiologist involved with that. But important to recognize it on a smear, right? And no. And because they may or may not have sent for for a parasite analysis. So like, please send this patient for parasite analysis. The next time to febrile because it's only if you would have thought, oh, maybe they have malaria. But if you don't know, if they didn't tell you the travel history, the patient didn't tell you, you know, it's possible they might be clinically. It might not be obvious, right? Right. Or if you know, you get peripheral swingers from other places and you have no history. Oh, yeah, you just don't know. But this can be decided is not the falciparum. Give me the site. Okay. Knows. Yeah. So I've seen those before, like little horseshoes and rings. Yeah. And there's more up there, right? Yeah. So this is like the headphone for headphones. Yeah. It's got the two nuclei. I don't know that's an official term. I like it. In a ring form. And you'll note that there are multiple ring forms in one red blood cell there. And then look at the difference in that commute a sight. Oh, yeah. It's a little bit folded, but you can see it's like, yeah, almost a sickle shaped like it's a long kind of oval with all slightly pointy ends. So totally different than that last one, right? Which is a totally round. Is this the falciparum? And so the food analogy here's banana shape, the opening of that way. Yes, banana. That's folded itself. And there's the malarial pigment. Pigment, which basically came a little bit big break down. Interesting. Oh, wow. Compared to this one. So there's a whole bunch of organisms here in the same. Yep. Same cell. This patient did not travel outside the US. I want to say like anaplasma or something or early ehrlichiosis. But I will show you that one. Okay. It's been a long time as you can tell since I've thought about maybe I should have studied before making this video. Okay. So there are some some things here. One point up there are ring forms outside the red cell. You see in malaria. And there's this structure which is either called a tetrad, oh, yes, I wall tees cross. Right? I can see that. Okay. And this is actually a tick-borne parasitic infection. Hmm. And this is boobies. Oh, my God. Yes, yes. I feel stupid 'cause I actually saw his that in training and actually have a slide of the smear, but I've forgotten. So clearly time to refresh my memory. Okay. But BZ, I don't diagnose dysplastic me by ohm on purpose. There you go. Hmm.

So that's a big blue blob in the cytoplasm of. I can't tell if it's a neutrophil. That's is it looks like it has tiny little granules here. It's either it's either almost segmenting or a band. Okay. There's not a monocyte, which isn't right, 'cause it's got granules and it doesn't have little vacuoles. I don't know what that is though. So there's the test answer. And there and there's gonna be the realize your wife answer. Okay. So if you see this on its hest, this is in a plasma phagocytes offal. Oh, because if you saw in a monocyte, you would pick ehrlichia champions. You're lucky. As in monocytes, anaplasma is in neutrophils. Uh-huh. Now here's the real life Anzio. This is actually ehrlichia link. Yeah, it's usually a canine ehrlichiosis, but we've had at least a couple cases in our geographic. Wow. You have to use molecular to sort out the species. Our PCR. PCR. Wow. That's cool. I mean, no, yes, because that's that's one of those like, you're calling emergency call. Oh, really? It's a real fast. Really, really. Yes. I don't really have a good concept of like what it entails clinically. I don't know. I don't recall ever seeing a patient with him. I mean, I'm literally dropping everything at that point, finding a clinician to call and getting them. Well, that's good. And you know, see that'd be something so easy to overlook, right? If you didn't know to look for it. Oh, yeah. It's that was not my first rodeo. So I saw that, I knew what I was looking at. And the first one I saw also ended up not being in a plasma, ended up being really good wink. Yeah. So sometimes the diseases don't read the books, right? All right. Mm-hmm.

I feel like these are mostly lymphocytes. Probably. They're going round and dark nuclei and they've got a little tight rim of blue cytoplasm. And there seem like there are more lymphocytes than there should be from what we've seen on the previous ones. So when I see that, I would wonder about like maybe CLL SLL. And you're saying that because there's a smudge cell always that I actually, okay, I didn't actually know that. But now that you say it, I do remember hearing. I just thought when I see an increased number of lymphocytes that look like small normal-ish lymphocytes, I always think, oh, CLL. SM+ it's really common, right? So this is a trap. Oh, I'm sorry. I trapped you on purpose. Um, because not all smudge cells are CLO. On a test, you see small mature lymphocytes and so she picks yellow. That's all. A move on. Um, I honestly have seen more smudge cells with viral illnesses. Home. This is neither one of those two things. Okay. So here's a higher power picture. This is a small site. This chromatin is mature. It's got the thin room cytoplasm, but look at that blue compared to this blue. Different color for sure. This is a darker blue. There is a nucleolus here that's sort of faint, but you can see. Yeah, it's like a darker color of the chromatin in the middle. Okay. And then you have sort of a roundish but slightly irregular nuclear contour. Noel rods. This is actually B A L L. Hey, well. And that is before the mm. We still use B A LL sort of colloquially. Such a blast too. Yes. QE lymphoblastic leukemias, o is the technical now classification, but it was the entity formerly known as AL. Right? Right. And it's so much easier to say it that I think it's gonna be a long time before that name dies out. Has been around for so long, right? Think it ever will? Because it's less of a mouthful. And when you're telling you patients, families, what it is, you know, which one are they going to remember? Yes. And now wait, is this an hour rod here? It is an hour. So is this a myeloid leukemia? Ven? Well, maybe. Yes. That is also the test answer. I, my world was shattered a few months ago when I read that some BLS have our rod like inclusions. The one certainty I felt like I had is that if you saw an outer rod, you had so sort of, you know, acute myeloid leukemia. So you're so be careful. So the point is that this cell right here is a lymphoid blast. And this cell here is a myeloid blast. But it could be easy to confuse those. Oh, absolutely. And you sometimes get a lymphoid blast that look exactly like that, usually to the owl rod. Morphologically, it's not a really good way to go. I used to tell residents if you saw an owl rod, you could call like acute myeloid leukemia. And now I feel like I can't tell them that anymore. The common things being common, it's most likely going to be acute. I feel the same in all parts of pathology. Anytime there's a rule that I'm like, this always works, eventually I will see something or someone will publish a paper that makes it like, well, this always works, almost always. But then every once in a while, there's a rare exception, right? Eventually, all the rules get broken in in medicine, I think.

So the next step, if you see log S, you're gonna tell me, okay, there's a lot more whites. Also should be exact. Huge. Way bigger than the red cells, right? So there's a what we call leukocytosis. So in those white blood cell count, I think those are blasts, but maybe I'm wrong. Maybe they've got little blebs coming off the cytoplasm. I can't remember if that means something or not. There, there's also this like kind of orange e color in the cytoplasm here, like little strands of orange stuff, but I don't know if that's meaningful. So those are a bunch of Elrod's. Oh, there are a bunch of our rods. A bunch of elrod. And then yes, probably meaningful. Look at how they're sort of this is gonna say, is it monocytic? Is this this stuff monocytic? It's not. No. So I learned it his cottage loaf. And cottage. It's a it's a British bread. So if you watch the Great British Baking Show, me, okay? And I was so excited because every time I say cottage loaf, people look at me like I'm crazy. But it's the term my mentor used. And I actually love it better than by lobed or like hourglass or any of those because it often is bigger at one end than the other. See how that's better? And that's what they do with the spread is they have a bigger ball on the bottom and they have a smaller ball on top. And then they stick their finger through to connect them. If you're watching this video, please go and find that Great British Baking Schepis ode and put a link to the cottage loaf episode down below. The first person to do it, I won't give you any prize, but I'll give you a special bonus point in my heart. I've actually been fun is to have people go and see how many of the analogies that we have here they can put videos below. So feel free to do that if you like. It will enrich the video experience for everyone. So this again, is is sort of an important findings. Okay. Now all I can think about is how much I want to eat some cottage loaf. I'm not sure it tastes like with bread. Sounds real good. I'm hungry. I've actually made it before. It is actually pretty. I want a piece. Next time you do it. All right.

This is AP oh, oh, so acute promyelocytic leukemia. And this is the really important one, right? It's just the really important one, but this is a variant of it. Oh, specific, less common variant. So normally with acute promyelocytic leukemia, you have pancytopenia and like rare. And I'm gonna call them blasts. I know they are technically atypical promyelocytes, but I'm gonna consider them to be blast equivalents for simplicity's sake. Okay. It's got very few circulating blasts. And you're like looking and especially at the edge of the smear because that's where they really have to hunt for it. You're hunting for them. And you're really looking for this cell here. Those cells with lots of our rods because that's going to make you think, oh my gosh, I really, really need to call people and rule out acute promyelocytic leukemia. This is the micro granular micro granular variant. And I prefer micro granular to high for an Euler because if you look at it and for electron microscopy, the granules are actually they're just really tiny. You just can't see them in there light microscopy. You know, these this is the one that you can treat with trans retinoic acid, right? A trot, trot, and they get better, basically, right? They work. If you have usually so there are variant translocations. Some of them don't respond to a TRO, but if you have the classic 1517 translocation, they respond very well to after us. So eight APL is sort of one of those things where pathology is really important because if you can get the patient through the first two weeks of treatment, they do extraordinarily well. Wow. Like there are almost I can't think of any APL patient I've had those relapsed. That's amazing. So they do extraordinarily well. But then they're the ones that come in and they're already in DIC or they're already have brain feeding. Oh, and they get coagulopathic problems with this disease too. Is that's a granule? So tissue factor in those great. Oh, okay. This is all coming back to me now, very slowly. So so basically, they either died right when you diagnosed them, Oh, or they do exceedingly well. So it can be in the middle. So it's really one of so these these are urgent phone calls. The ones that will bring me up at 2:00 in the morning to look. Wow. Bring my flow tech in for overtime payment and all that other good stuff because it matters right away. It matters right away. And they have a pretty specific flow immunophenotype that can help. Okay. Um, and I say pretty specific because there is something that commitment, but really like fish and PCR for 1517 or just a rah-rah translocation is going to be your diagnostic. Okay. That is the peripheral blood of someone who has the more classic APL. And it kind of has that same bi-lobe, you know, Carl of ich nucleus, but see the granules? Yeah, lots of granules. And I mean, this is not really a great picture, but is like one of the only cells that is in the peripheral smear, which is why it's there. Wow. Mm-hmm.

Chromatin on those white cells looks, I don't know, spongy. I don't know if that's the right word, but it looks like it's got a little tiny white holes in it. And then there's there are some tiny pink granules, I think in that blue cytoplasm. I see some granules there. And I feel like that's like got a fold in the middle. So I can't reverse. This is again, they makes me think of something like blasts, but I am, I my knowledge of blasts is very generic. And I'm just like, oh, anything that's weird and a white cell and I think it could be a blast, but I don't. A blast. These are probably your pro monocytes. Romanus. They're considered to be Blas equivalents. So they're okay, but they're a little bit more. Yes, well, they're blasts of cool events. And what this is, which is myeloid leukemia. Oh, what used to be a cube myeloma monocytic leukemia, or is it different? It can be either. Milo monocytic, or can be acute monocytic. Okay. So if you have two different blast populations, one that is more myeloid and one as acidic, or I mean, that's generally how it happens. Even my little monocytic, and you cannot just peer models, but either way, it's a sub subcategory of a Q myeloid leukemia. So in der map, these are the ones that we tend to see showing up as leukemia cutis, right? Because though particularly the ones that have the monocytic differentiation, either my lamont aesthetic or monocytic, they for some reason home into the skin, it seems like, and they love to come to the dermis. And so you're a little bit by some what you seek is going to be even if you have myeloma say clicking it, it's the monocytic component that comes today, right? And this makes sense sort of biologically because what to monocytes do? They turn into history sites, are you trash your peripheral blood? So your monocytic ones are more likely also to be in your CSF. Okay? So they're equipped to do the same things that normal monocytes and macrophages and history say, I mean, they don't function normally, but they seem to have that ability to get out of vessels and go into tissues. Huh? Interesting. And this is really going to be your differential for your micro granular APL because remember, you're listening because yeah, there's the granules there. And there's not really good vacuoles. Are there? No, there can be. And so everybody's blast look a little bit different. Okay? I mean, I don't think I've really seen two blasts that look exactly the same. So something you can do is like pull previous pathology and compare blast to blast. And is this what you mean by so the the blue color here, that real deep blue, is that helpful or just just pretty to look at? I don't understand. That's usually your immature cells are that deep, deep blue. Okay. And the only exception to that or plasma cells. Oh, yes, blue again, but mostly your immature cells are the ones that are going to that deep, deep blue cytoplasm. And this is half more that blue craze. Yeah, but they're not as mature as I would like that that nuclear chromatin to be to call again. Okay. This one's getting there. This one, you could almost, and I wouldn't really blame you for calling it an atypical monocyte. I would call that a pro. Okay. How do you tell though that this is, I mean, I can look at that and I say, I think that may be a blast, but as opposed to like the downy cell earlier, the reactive thing, is this what you mean by being a bully? It's not at all yielding to the red cells. It's just around and pushing him out of the way. Exactly. Okay. Out of the way. That can be sort of a soft sign. No, I have seen blasts that have not quite been bullies, like there. Okay. Nicer blast of the red cells. Uh, but it's sort of one of those soft signs. You can sort of help yourself. And again, clinical information is going to need key because if you have a kid that has all the mono symptoms, infectious mononucleosis, you're gonna be a little less scared than, oh, I have this 80-year-old who's coming in with, you know, leukocytosis, anemia, thrombocytopenia. That to me is. And what else helps you here? Is this something about the chromatin? The shape of the nucleus? The size too? Or just the fact that it's a white cell that doesn't look like any of the normal ones? Well, I know that's really simple and basic, but I just wonder like, what what things they're all of the above. So this cell here comes. And this cell here, I mean, that's a really like oddly shaped nucleolus. Yeah. Um, and nucleoli are seen in cells that are either immature or cells are active. So remember those. Oh, yeah. It's can have super white cells in the blood. You shouldn't normally see nucleoli. You can't in really reactively. Okay. Does, um, but it's something that you're like, paying attention for. Okay. There's a nucleolus here. Maybe I should look at it a little bit harder. That's good to know. It was another tissue. Sometimes nuclei are like normal, right? We see outside of the blend. Do you see how this is a little bit more violet? And this is a little bit more purple? I know that's dumb sounding, maybe. I, that's how I started to look at the chromatin patterns and I recognized more open. Is I felt like that looked like a slightly different shade of purple than this. Okay. And even this compared to this, I can see that there are color differences. So as I said, I think this one is the most mature out of all of them. This one, you know, is still immature, but it's more mature than this. And that's partly because of this, you know, cytoplasm. And it's slightly because this chromatin pattern to me looks different. Now it's got like pale areas in here. Is that it's just more open? And we call that. Okay. Yeah, there's their spaces that are kind of pale. Sure. Yeah. Um, now I will tell you that when my mentor started telling me that salesmen different chromatin patterns, I thought she was crazy. Well, that's why I'm asking you because I think it's easy for all of us as pathologists, we get used to looking and recognizing. Once you see something enough, you're like, that's just what it is. But it's always hard, I think, to explain. And I have to think through a lot how to explain what I'm actually looking at when very junior trainees sit with me and they're like, well, how do you know it's a male on a site or whatever? And I have to think through what are the exact features that my mind is picking up on. And it's sometimes hard to verbalize. I think it, it, I will tell you, it took me years for it to actually like it. And like, I don't know, there's one day that there's sort of like a light switch moment, but honestly, she would sit at me with the scope anyway, is this a reactive lymphocyte or a monocyte? And I, that's priceless. I mean, I think that experience of again and again, back and forth, is when you finally pick up the new one. So if you're watching this, dear, dear viewer, and you're like, those all look the same, don't feel bad because I'm in the same boat as you. I just need to sit with Dr. Ramos a lot more clearly. Well, and to be fair, they are all similar. I probably would count them all in the same category. Okay. Um, 'cause again, pro monocytes are blast equivalents. So you're seeing any of these in the blood is problem, right? Pretty much. Yeah, because even if this isn't a typical monocyte and not a pro monocyte anymore, it's still atypical. Aha. And it shouldn't be there. You shouldn't be there. Okay. Mm-hmm.

So those remind me a little bit of the downy cells, but I noticed that they're pushing. They're not doing the Dutch skirt merging around. They're pushing things out of the way. So I wondered if maybe they're like lymphoid blasts, but you're going to tell me they are something totally different. So honestly, when I would look at that, my gut reaction would be like, circulating lymphoma cells. Oh, okay. Or AML blasts. AML blasts. Oh, okay. Which is part of my everybody's blast look different. Yeah, I feel because those are AML blasts. And that is the circulating lymphomas. Oh, oh, wow. And so it is merging around its neighbors, but that doesn't matter. It's actually lymphoma in this case. Yeah. And look at that nuclei. Yeah. And then again, sort of when you get your diffuse large B cell, which this happens to be searched, oh, you can get that blue back in the cytoplasm. Sister relating lymphoma cells can mimic blasts. It's one of the reasons why I am really reluctant to call blasts outright. And who I have flow, because I've seen lymphoma cells manic blasts and vice versa. Have you even seen plasma cells that I thought were blasts? And then and then the person who who did the workup was an experience, like I really experienced amount of pathology. He started off with the blast screen. They needed a lymphoma screen. And then he finally added the plasma so. And they were plasma cells. Sebacean had myeloma. The patient had well, plasma cell, too. Other team. And then, yeah, myeloma. But as you've taught me, one of the one of the many things I've learned from you in the years we've worked together is that plasma cell neoplastic processes can look wild and crazy and weird. And plasma cells when they're neoplastic or dis crazy or whatever, they don't necessarily look like regular plasma cells. I've seen once it looked like high-grade lymphomas or blasts in skin. And then you were like, well, I think it could be plasma cells. And sure enough, it was. So that really opened my eyes. I was blown away by that. Yeah. So I think that plasma so neoplasms are sort of like the melanoma. Look like anything. So so the point is, this person probably had a large B cell lymphoma, like in a lymph node or a tissue somewhere. And then some of those cells got in the blood and floated around, right? And then the tech probably turn this in for blasts. Yeah, because if you didn't know the history, you would think it's a blaster. Absolutely. Or that the other thing you have to consider is that patients that have a history of lymphoma and then get chemotherapy can either have recurrence of their disease or can get a therapy related myeloid neoplasm. Oh, technically also interesting class, which is why I hold off. Well, then let me ask you, I'm sorry for diverting again, but nucleoli. You know, I think in on H and E stand, you clearly are often like kind of a purpley red color, but here this is like a circle that's kind of hot less pigmented, like paler than the rest of the nucleus, right? Yeah. And so, but but I think some of the ones we shed early, they look darker, but anytime you have like a little circular area of different color in the nucleus, that's probably on nucleolus. On if it's distinct, like, okay, cool. That's helpful. Mm-hmm.

Well, I feel like we've got a and regular neutrophil there. I can't tell that's regular and just fold it funny or if it's a badge. Maybe that looks like something abnormal. I don't know what those are. That looks like an e. Oh, maybe we'll see how wrong I am in a minute. And those I think are kind of a blasty or in the blasty type lineage, but I kind of wonder if if there are different levels of maturation, like as they all look kind of different from each other. All right. So now tell me how about it. So that's a basic bill. Oh, and that's a video. The granular remains a filigree. So remember the bit the basic fill I showed you before, you know, oh my god, any side d granulated. So that's more of a purple. Okay. Then that that Barbie pink. Yeah, neutrophil. Probably either proud. I would say seg, because I can see there's a yeah, okay. That's just a funny fold. Okay. Myelocyte. Myelocyte. Myelocyte. Either a meta or a Milo site. Sort of got that dawning of neutrophil iya. So, oh, I remember hearing that a long time ago. And then that's a blast. A blast. So they are kind of they're all myeloid precursor cells at different stages. So what is this? So then does that mean this person has chronic myeloid leukemia? CML? Yes, because you get a range. You don't have enough blasts, right? But but and you have different levels of maturation. Okay. Right. And this ended up being chronic phase. So there were less than 5% total blasts and cool blood. So I say that the CML sort of looks like the bone marrow has hit the peripheral blood alone. Did you have all the stages of maturation? You'll often see a mile a site bolt. Again, I was like, oh, oh, I see. And then you get a basal fill. Yeah. And you often will also get an absolutely is enough. Oh, yeah. Okay. But CML again, can be, you know, can present feared a lot of different ways. You can even just get a thrombocytosis. So the real way to diagnose CML is to do the 922 translocation test. Okay. So your BCR Abel. And these milo sites did kanay a little bit like monocytes, or I guess monocytes have that like a more. Yeah, so if you look really, really closely, so these are young monocytes 'cause they've got that blue tinge where monocytes in the myelin, sorry, Milo sites. Okay. They're they're young web sites because they have a little bit of that blue tinge. Yeah, they're they're getting their secondary granule. Oh, okay. I see. So they've transitioned from the promyelocytes stage where they only have primary granules and now they're getting their secondary oils. Um, this is a little bit of an older Milo site. And you can see that inside of us looks more like the neutrophil. Okay. They're still Milo site, just, you know, in the book it looks like things go from here and then jump to here. And then I personally like to give things the benefit of the doubt. And if it's sort of an a tweener, I give it the benefit of maturity. Okay. That's helpful. That's good to know. Uh, I'm not saying that's right or wrong, it's just what I do consistently. I think so. You should be just consistent and what and know what you're gonna do it. Why? I love that you said that. I think in in my areas too, when I teach, I say the same thing. I don't necessarily know if this is the best or right way to handle this, is just how I do it. And I try to do it the same way every time. And I think that's what a lot of times people want to know, like people who, you know, you see this all day long and you've found a way to handle something practically. And that's the hardest part sometimes with pathology is knowing how to practically work through things. Mm.

There's lots of white cells here and they all look different shapes and sizes. It's important to know that this is a two-year-old. Oh, yeah. I see vacuous here. I think that might be a monocyte, but you are not saying anything. Oh, is this you? You're getting a good poker face. I see little granules here. I don't know for sure what that means. You're pointing at that. I wonder. I seem to remember that kids with maybe Down syndrome get something unusual where they get lots of white cells that gets confusing leukemia, but I totally can't remember what that is anymore. So that is yes, yes. Um, but that's normally in the newborns. Newborns. Okay. So that's called transient and my little pieces. Okay. And that usually goes away. And and usually again, happens in the first few months. Okay. Not in a two-year-old. And it's important to know that that happens in those patients because they have a 20% more risk of getting the leukemia at age two. Okay. So it might come back as, oh, okay. That's good. I didn't know that. It doesn't. You don't have to have Tam to have the leukemia. The transit abnormal mile appeases. Ah, but if you have that, you may have.

A higher, but you might have a higher risk of getting the leukemia. So they'll probably watch a little bit. Okay. Oh, I don't know what's going on here. I feel in that maybe this is maybe, yeah, okay. But yeah, I'm impressed by all the various shapes and sizes. I don't understand what we'll talk, but let's compare that. You see that pink? Yeah, to that. Oh, yeah, that is more purple. I see what you're saying. Okay, okay. So this is a blast. Okay. These are abnormal monocytes. Okay. Not a site-to-site, probably a lot of site on a site, may even be another blast. All right. This is actually JMML, so Juvenile Myelomonocytic Leukemia. It is normally seen in about age two in Korea, associated with neurofibromatosis type 1. Oh, that's right. But does the only reason why I gave an H with this one because it's important to note the age for this diagnosis. Those to me look like, okay, now, okay. These look like mature lymphocytes, I think, but there are too many of them. And these are smudge cells. So unless you're tricking again, CLL, okay, chronic, chronic. All right. And that's what you pick on a test and you move on. Okay. Hmm. Oh, ground nuclei with blotchy. Oh, I wonder are they did any plasma cells? Maybe I see like a clock face or chocolate chip cookie pattern. I like chocolate chip cookie. So, but blobs of dark in the chromatin pattern, like your little blobs, and they're kind of eccentric. They've got cytoplasm out here and maybe a little touch of a perinuclear hof, like a pale area right there. Is that right? Or is it wrong? Right? Yeah. Often I've seen with the circulating plasma cells is that the perinuclear hof is not as prominent as it is. Yeah, definitely looks yeah, different in tissue and really easy to see. I kind of thought of lymphocytes at first, but they had too much cytoplasm. And then, then I noticed the chromatin look kind of weird, right? And so you can have them look like this, and then you can have them look really amazing how different cells look on a Wright stain on a smear than in tissue on H&E. Mm-hmm. Again, they kind of wonder about a plasma cell because it's got like a little hof, and then the chromatin, it's a little harder to see. And then this, I'm not really sure. It's a neutrophil. And I put it here. Oh, is that roll? Oh, yeah, that's real. Rouleaux formation. And so that is actually a plasma cell. And that you get in Waldenstrom's macroglobulinemia, or can you get it in any sort of myeloma that rouleaux formation? Oh, yeah, you can't in Myeloma. We can also get it with some autoimmune diseases. So they're all sticking together, right? Again, like a stack of pennies or something. Oh, I use M&Ms and Rolo's. Oh, that sounds too. You know, multiple myeloma, which we don't really use anymore, plasma cell myeloma, but just, but it takes away my my way. So I put the candies together. So, mmm, so multiple myeloma. And you know, those Rolo's that are the little caramel filled chocolates, yeah, they stack up and they don't just touch, they stack. Yeah. And that's important. And there's got to be at least four of them. Oh, okay. They have to be stacking at least four. So this up here would count one, two, three, four. Yes. Okay. So that's nice. Okay, cool. Mm-hmm. I, I think that's a giant platelet. Huh? Yes, cuz I'm gonna say I don't even know if that's a nucleus. It doesn't have like a border around it. It's all like just granules all chunk chunk together. And it's the whole thing's bigger than I read something, right? And so probably you counted as a red cell incident. Oh, is it on the Coulter counter? The counter like checks by size? Partly, right? Okay. Yeah. Oh, these are platelet aggregates, right? Right. And these are lawns. So this is someone I told you we talked a little bit more about EDTA. Yes. So this is an EDTA artifact. Hmm. And in some patients, this happens. Well, you can recollect in a sodium citrate or lightly talk to you. Okay. In a platelet count off of that, and that usually will help resolve. Now, is this, this seems like more white cells than there should be. Is it because we're in a thick edge of a specimen? Okay, like this is where the, this smear comes to an end, right? Yeah. So the density is higher. I wasn't paying it. I don't know what the white count. Oh, I see. Care because you were just trying to get the platelets, right? The platelets, they may be a little bit higher, but I honestly can't. Oh, okay. No, that's fine. That's good. Um, because I'm pretty sure this patient would have a thrombocytopenia. My machine. Oh, because all the platelets are all clumped together. So it looks like they're, they're lower because, right? So your platelet count is going to be inaccurate. Okay. Oh, that means something. Those are platelets sticking to the outside of a, I think, neutrophil, right? Yes. Oh, I got, I remember that picture from studying for boards, but I can't remember now. What is it mean? They're covered in like antibodies or something to autoimmune? Well, oh, it's an artifact. Okay. I'm sure we're seeing it being it was pretty. And then since they're sticking to the neutrophil, think you count with the neutrophil because none of these guys normally, these would get counted as whatever, ten platelets, but now they'll get not counted at all because you're going through the machine with the neutrophil. Okay. Right. They're hiding out. Really cool. That's a little tiny blue guy and has got some little speckles in them. So is that our reticulocyte? Are you saying you can't tell that unless you do this special stain? Right. Right. And I want to say there's something you can get salsa like that methemoglobinemia or I don't remember. Okay, I give up. That's a hypo granularly hypo. That's a platelet. Okay. It's a large platelet. Okay. Um, but remember when I showed you the neutrophils that were hypo granular and I posed, I meant, and this is the platelets in the same patient. Oh, okay. So they also show some dysplastic findings and larger staple granule. Yeah, it's a lot harder to recognize them when they're big and then don't have that. Well, and you can see how this can sort of get confused with those. Give me this. Oh, yeah, sure. That look a lot like a commute aside from malaria. Oh, you have a hard job. Okay. Those red cells look abnormal. I'm guessing that's an artifact, but I don't know. And there's a bunch of blue in between. The blue in between is what I want you to see. Well, I mean, I'm since we just looked at hypo granular big platelets, I would wonder if it's a bunch of those, but I'll see like any granules at all. I don't know what that is. Those are cryoglobulins. I con a sphere. Whoa, that's amazing. Very different than like we see cryo sometimes in skin and it looks like pink bright pink stuff that's filling up blood vessels, kind of like fibrin. Very different than that. Amazing. So the red cells are actually not abnormal. That just crunched up against this, right? Is is pushing them out of the way and making them look. We are, huh? Wow. This is really cool. I feel like I've learned a lot of things. I don't know how long I'll retain them, but thankfully we'll have a video that I can watch again if I need a refresher. And I'm not saying this is like all, well, we'd be here. This is why we have fellowships, right? On end, but there's some interesting things. I think some good tips. Cool. Well, thank you so much for sharing all of that knowledge with us. And I will put some links to social media that Dr. Ramos helps contribute to down in the video description. And also a link to her lymph node lecture if you haven't seen that yet. I highly recommend it. It's fantastic. And please let us know what you think about the video. Comment below. And if you want Dr. Ramos to come back again for third or even more visits to give us some heme path knowledge, let us know. And let us know what you think she should cover. So thanks again for watching. And please consider liking the video and subscribing to the channel if you want to be notified of more videos like this. Have a great day. Thank you for joining us, Dr. Ramos. Thank you.