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S2D: The Symptom to Diagnosis Podcast - Episode 09: Anemia
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S2D: The Symptom to Diagnosis Podcast - Episode 09: Anemia
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Segment:0 .
DR. CIFU: I'm Adam Cifu.
DR. STERN: And I'm Scott Stern.
DR. CIFU: And we're back with episode 9 of the Symptom to Diagnosis podcast. For those of you who've been with us this far, you must be sick of the podcast introduction. So Scott, let's just jump right into it. Our case this week is anemia, which I always think is the problem with the most classic internal medicine differential diagnosis, right?
DR. STERN: Right totally.
DR. CIFU: So you're the expert of the day.
DR. STERN: I like that.
DR. CIFU: You got new glasses.
DR. STERN: Well, reading glasses, they have lights on them, so I can really see in the dark. Anyway--
DR. CIFU: Well, that's the nerdiest thing I've ever seen.
DR. STERN: [laughing] Thank you.
DR. CIFU: Anyway, so you're the expert of the day, you want to present a case today?
DR. STERN: I do, and I'm going to stump you on this one. I'm just giving you a warning. [chuckles] This will be fun when you're squirming. Anyway, I saw a 65-year-old man many years ago now, who had self-diagnosed sciatica, and he actually went to the emergency room because the pain was so bad that he couldn't get any relief. And believe it or not, he was actually admitted for evaluation and treatment because he was in so much pain, which as you know is really bizarre.
DR. STERN: He noted severe pain radiating down his left leg for the last month. He tried Advil, Tylenol, gabapentin, physical therapy and nothing was giving him any relief. And his pain was 9 out of 10, waking him up at night, it was really awful. On admission he had some labs, and they included a CMP that was unremarkable. His CBC revealed a hematocrit of 28, and his hemoglobin was 9.
DR. STERN: So, that's the case.
DR. CIFU: That's all? You're kidding me?
DR. STERN: That's it, you're on your own.
DR. CIFU: Okay so, you're keeping a lot of the things that I was hoping for away. But I guess maybe I'll frame it in that, if I'm walking in to see this guy, what strikes me is 65-year-old guy, not only anemia but back pain, which he's calling sciatica, but whatever, we'll just take it as back pain. So, I guess the things that would go through my mind at this point would be some bad things, I would think about what could cause anemia and back pain.
DR. CIFU: I guess I'd think about malignancies, could this guy have prostate cancer with metastasis to his spine? Could he have myeloma? Right? With maybe a compression fracture? I guess I didn't quite get the acuity of this all, but maybe if I go crazy and say, it's acute, could this be an infection? And the guy has got infection like, I don't know, spinal osteodiscitis, even bacterial endocarditis, right?
DR. CIFU: Maybe that's causing an anemia of inflammation. I guess the back pain could be sort of true, true, and unrelated, and the guy could just have your basic iron deficiency anemia or B12 deficiency. Maybe that's sort of what I'm thinking. I guess, my next steps-- I'd obviously examine the guy, I'd see if he had tenderness in his back.
DR. CIFU: Maybe flank tenderness, does the guy have an obstruction and has the anemia because of chronic renal insuffiency, because of obstruction, that's probably a bit of a stretch, but I'm lost here. And then where I always start, I'd say, I'd like to see his retic because I want to know, is this underproduction or not? I'd want his MCV to help frame the differential for me. And you're particularly cruel by actually only giving me a hemoglobin.
DR. CIFU: So I'd certainly also want to see his white count, his platelets, is this pancytopenia or not? And I'd like to see a smear which often doesn't help, but sometimes it really helps. So maybe that's what I have to say.
DR. STERN: Well, that's great, I just want to point out one thing that you've done automatically, which was really critical in this case, which you say, he not only has back and leg pain, but he has anemia. And oftentimes in the hospital, you know what happens is so many people are anemic that the anemia is ignored. Oh well, they're just anemic, because everybody's anemic. But he doesn't really have a history that suggests he should be anemic.
DR. STERN: And what you're taking for granted, is you're immediately trying to put those together. And actually, the house staff that was seeing him at the time had completely ignored his hematocrit and were solely focused on his back pain.
DR. CIFU: It's interesting, I think the problem with that is that we all learn Ockham's razor, right? The whole idea, parsimony, try to figure one diagnosis that covers everything. Though, people also toss around Hickam's dictum, right? That you can have as many diagnosis as you damn well please. And often in the hospital, people have so many diagnoses that there's less of an incentive to actually come up with one unifying diagnosis.
DR. STERN: Well that, and anemia is so common, because so many people are so sick in the hospital, that it's almost taken for granted, that everybody in the hospital is anemic. But this is a guy who was otherwise well before, and is now clearly anemic. And if you don't dive into that, and you don't figure that out, then for sure you're missing something with this--
DR. CIFU: Totally, totally, good point.
DR. STERN: So, I think now maybe what we'll do is take a deep dive into anemia and then come back to the case, or would you like some more data first?
DR. CIFU: No, no, let's do that. So usually at this point what we do is you give us five points, and I just try to say smart things as you go through.
DR. STERN: Okay well, good luck with that one. So, my first point you've actually already stolen from me, but I'll repeat it, which is, it's always important when you think about someone who's anemic, to look at the smear, as well as the white blood count and the platelet count, in addition to the hemoglobin, because sometimes you get critical clues. I mean, obviously a smear can sometimes show you schistocytes or sickle cells, which can help make the diagnosis of either hemolytic process or sickle cell anemia.
DR. STERN: And also the white blood count and the platelet count can sometimes be very revealing. I told you about a patient, another patient I saw recently, who I got a stat lab called for, 65-year-old guy who came in feeling kind of tired, nothing else specifically and I got a CBC just to see, and at like nine o'clock at night, the lab called me and said his white blood count was 6.2. It's an emergent value.
DR. STERN: And of course the most--
DR. CIFU: His hemoglobin.
DR. STERN: His hemoglobin thank you, was 6.2 and the immediate knee jerk response it's probably another guy with iron deficiency anemia and colon cancer. But actually because, I've given this lecture many times, I immediately asked the lab for his white blood count, and his platelet count. I said, hang on for a second, so I went back to check, and his white blood count was 2, with an absolute neutrophil count of only 420, and his platelet count was 129,000.
DR. CIFU: Wow.
DR. STERN: So this isn't anemia, this is then pancytopenia which has a completely different differential, and you always of course worry about leukemias in that situation and indeed, this was his presentation of AML. So, first point is, look for pancytopenia first.
DR. CIFU: Your question about the white cell count was good because, A. it helped the patient and B. you would have just gotten another call like 20 minutes--
DR. STERN: [chuckles] It's totally fine, they would have been waking me up again, you know.
DR. CIFU: Okay, so that's point one, what's point two?
DR. STERN: And you said this as well, and the second key point is to look at the reticulocyte count, I just want to emphasize that. Probably I would guess that 90% of the patients that we see in the hospital and outside of the hospital who have anemia have an underproduction anemia, the most common ones being iron deficiency, and anemia of chronic disease. But, every now and then, maybe 5-10% of patients have hemolysis and the real clue to that is often going to be that the reticulocyte count is high.
DR. STERN: It's often not evident on the smear, and all those causes whether it's TTP or G6PD deficiency, or autoimmune hemolytic anemia, you're never going to make that diagnosis, if you don't get that reticulocyte count, so that's next.
DR. CIFU: They always talk about these days kind of systematic solutions to errors. Do you think that a reticulocyte count should be automatic with a CBC, or maybe at least the CBC with diff?
DR. STERN: Well, I think it should be triggered by the anemia. So, maybe what they could do is have an automatic reflex response like we do for HIV tests, do a follow-up, that if the person's anemic, you get a retic.
DR. CIFU: Right so, if the person's anemic and their last CBC was not anemic there's a retic--
DR. STERN: Exactly and that's a good point to add because so many people are chronically anemic you might not want to do it each time.
DR. CIFU: I think that'll be helpful.
DR. STERN: Yeah.
DR. CIFU: Okay, those are two great points, what's your number three?
DR. STERN: Well, the third one is again, you mentioned this, so you did very well, I'm very proud of you. And that was the MCV is a good guidepost, but not a hard and fast rule. Obviously macrocytosis suggests, but doesn't confirm B12 and folic acid deficiency, and other forms of macrocytosis and microcytosis can suggest iron deficiency, thalassaemia, chronic disease, but there is considerable overlap.
DR. STERN: But the MCV certainly gives you an important clue and that will be next.
DR. CIFU: Great. I'm going to maybe blow one of my points that I was going to use later in this, but I always say that the MCV is incredibly good at organizing your differential diagnosis, but it is not a diagnostic test.
DR. STERN: Yeah, I mean, it's definitely-- at least a lot of diagnostic error, right?
DR. CIFU: I agree.
DR. STERN: We'll come back to that.
DR. CIFU: Point four?
DR. STERN: Point four is iron deficiency is not a final diagnosis, you have to find the cause. Now in the world, the most common causes are obviously, women of childbearing years whose iron-- and in other parts of the world it's iron deficiency due to diet, but in the West, especially in post-menopausal women and in men, it requires an explanation. And it's often, as you know, due to occult bleeding from a colon cancer, or stomach cancer and so on.
DR. STERN: And so, if you stop the workup in someone who has iron deficiency anemia, who's a post-menopausal woman or a man, you've really committed malpractice.
DR. CIFU: I actually like things like that. This is on the order of, you know, older person comes into my office with dysphasia, when there are things like, "That's great, I don't have to think about this one." You're an older person, iron deficiency anemia. Okay, you know, I got a skimpy, I got to figure this out. You come in and you tell me that food's getting stuck in your throat. Whatever, you can keep talking, but I know what I'll do.
DR. STERN: And in a way that does make practice easier because when you understand that these are just hard and fast rules, you don't worry about it. You just do what needs to be done.
DR. CIFU: And then you kind of start thinking, after the endoscopy's--
DR. STERN: Right, right, exactly, that's the way it goes.
DR. CIFU: Okay, and number five, bring us home.
DR. STERN: The last point is in chronic disease you need to find the cause. It's not okay to say somebody has the anemia of chronic disease when you don't get what that is. I mean, well controlled hypertension for instance, without renal insufficiency doesn't cause the anemia of inflammation and so on. And so if you don't have a cause, then it's a clue that something else is wrong, and to ignore that clue is really missing the boat.
DR. CIFU: And I think it's one of the reasons that we've gone from calling it anemia of chronic disease to anemia of chronic inflammation, because you need an inflammatory cause. But the hard part is then also, so many of our patients have so many problems, and you're like, "Do these account for it or not?" And, and it is one of the places that the kind of secondary tests of anemia, you know, iron studies and such, are often not really diagnostic.
DR. STERN: Well, where I find it helpful is when you don't know that something's wrong with someone and you get a CBC and you're wondering, is this really real? Is it partly somatic? How sick is this person? And then you find out they're anemic, and the person who you thought was well, and you say, you do the workup and it looks like anemia of chronic inflammation and you don't have an explanation, you know the dig.
DR. CIFU: Right. Good point. Okay, I actually dread saying this in this case, but let's get back to that ridiculous case that you presented to me.
DR. STERN: All right, so would you like--
DR. CIFU: I'd like to have a physical exam.
DR. STERN: Yeah, so his physical exam was pretty unremarkable. He was afebrile which is obviously important given some of the things you mentioned. His heart and lung and abdominal exams are unremarkable. Interestingly enough, his back was non-tender, his straight leg raise was negative, his strength was all intact. And just to emphasize, his pain he was calling sciatica, but his pain was really in his leg, up and down his leg.
DR. CIFU: Interesting. So hearing that, I guess I would ask you, did you really listen to this guy's heart? Did you make sure he didn't have a murmur?
DR. STERN: I did. I always do that and you know that, I have an electronic stethoscope that even given my old age, I can amplify this out, so yes I did.
DR. CIFU: And his leg exam, it sounds like, and tell me if I'm right, that it was pain that he was feeling, but you were actually not able to reproduce that on exam.
DR. STERN: Correct.
DR. CIFU: Huh! So, I guess the things that I think about then, I'd be considering, a marrow process, right? There are some people who, when they have a super hyperactive marrow actually get that kind of deep bone pain, this is pretty localized for that which makes me feel a little bit uncomfortable with that. I have certainly in my day seen people with pathologic fractures actually, where I can't induce anything, but their bone is just such a mess underneath that that's the problem.
DR. CIFU: And given that this is localized, yeah again, I mean, metastatic cancer, myeloma with plasmacytoma, those are all possible, but I got to see some labs here.
DR. STERN: So as I said, his comprehensive metabolic panel was normal. The residents - because the patient had come in with a self-diagnosis of sciatica - did an MRI, and it was kind of interesting, their thinking. So, they did an MRI, it was normal.
DR. CIFU: This is going to-- Oh, it was normal, okay.
DR. STERN: Normal.
DR. CIFU: I thought I was going to say, is going to piss me off because they made the diagnosis with the wrong test without thinking. But I'm happy it was normal.
DR. STERN: No, so it was really fascinating. So the MRI was normal, and I said, "So what do you think is going on?" And they said, "Well, we think it's sciatica." And I said, "Well, I don't really understand that. You've not shown anything compressing the nerve. And you're sticking with that diagnosis." And they said, "Well, maybe the MRI is normal, because it's just an error." And I'm like, "Well, how sensitive is the MRI?" And as you know, for a herniated disc it's exquisitely sensitive.
DR. STERN: And so they said," Well, maybe it's just missing." Then I asked them, "Why is he anemic then?" And they're like, "We don't know." But they were comfortable saying they didn't know repeatedly and I was not comfortable with saying they didn't know repeatedly.
DR. CIFU: And I assume this MRI was of the LS spine.
DR. STERN: Correct, that's right.
DR. CIFU: So it's conceivable that maybe there is something to see, but they're just imaging the wrong place. I've had this conversation a lot over my career when people order a test, it doesn't show them what they want and so then they ignore the result. And it's interesting because often you say, so why did you order that test in the first place? And it's not really the ordering the test that's the problem, it's the reaction to it.
DR. STERN: Right.
DR. CIFU: Because in fact, with some tests if your pre-test probability is really high, and the test is negative, you should still believe the diagnosis, but your next step should be, I got to do something else, not "Okay, we're done here."
DR. STERN: Right and the other clue, I mean, not only would it be unlikely with the MRI being so sensitive, but there's another phenomenon, his anemia that they haven't explained, and you put those two things together and it's like, okay, something's wrong. That's a lot of anchoring bias. I think it's just worth pointing that out, right?
DR. CIFU: Okay, I still want MCV, retics. I don't know... PSA, SPEP, UPEP.
DR. STERN: Okay.
DR. CIFU: Blood cultures, CRP.
DR. STERN: All right, so let's go through it. So the CBC, the white count and the platelet count were normal, so it was not pancytopenia. And as you know, the next step was the retic count, which was low, his reticulocyte production index which is the eaiest way to decide whether it's underproduction, or overproduction was 1 which is suggestive of an underproduction anemia. His MCV was 85.
DR. CIFU: So let me just say, so we've worked through that nicely and this is the way it's laid out actually in the Symptom to Diagnosis textbook is, pancytopenia or no? And actually, I think it's not just pancytopenia is this pancytopenia, or is this hemoglobin and platelets which you'll sometimes see in destruction, right? So then we move on to, is this underproduction? And we find out that this is underproduction. And so this is where classically you'd get into is this microcytic, normocytic, macrocytic, and of course, since you're here to torture me, you're going to give me a normocytic.
DR. STERN: Of course I am, so his MCV was 85.
DR. CIFU: Which essentially helps me in no way whatsoever, and then I guess the other things where I would go next, honestly-- This is acute or subacute? Or like how long--
DR. STERN: The pain is about a month.
DR. CIFU: About a month. So I would send blood cultures, though I really think that's not going to tell me anything. I would do my PSA, SPEP and UPEP though to be honest with you, with a normal alk phos on that CMP with normal renal function, I think that's unlikely to show me anything, and I'd want some sort of imaging of that leg, whatever. I'd probably just start with an X-ray.
DR. STERN: So several things you did, I really like, which is-- I'm just going to emphasize them. You went to the MCV at the end of that series of steps. I see many people jump to MCV without having looked at the retic again and not looking at the full CBC, so that's great.
DR. CIFU: And that can really scr** you up because a high retic count-- this can actually give you macrocytosis, but just because their retics are being worked into it that's not telling you anything.
DR. STERN: Right. So that's terrific. The alk phos won't necessarily be elevated in myeloma, but the SPEP and the UPEP might be, so they were normal. And finally, what we did was what you recommended, which was imaging of the leg. And actually, I don't remember the sequence of events, but we actually got a bone scan first because we were stymied. And that showed multiple areas of high intensity throughout the bones in the leg, consistent with?
DR. CIFU: Paget's disease? [chuckles]
DR. STERN: No, so we took him to biopsy, and he had metastatic adenocarcinoma of unclear primary.
DR. CIFU: You suck.
DR. STERN: [chuckles] I told you it was hard.
DR. CIFU: That's a terrible case but really interesting. And so his anemia, I would really take that, to be sort of anemia of chronic inflammation, right? That the guy's systemically ill, probably chronically ill. And it has nothing to do with bone marrow invasion, just that he's sick otherwise.
DR. STERN: Right, exactly. But the reason I thought it was worth presenting the case, is it was really his anemia that was one thing that led us to say, we need to keep digging. And I thought that was really interesting.
DR. CIFU: Actually the real reason you presented the case was to make me look bad on our podcast. I will get back--
DR. STERN: [chuckles] I know I'm a little bit-- That thought's already crossed my mind. I might not show up for the next one.
DR. CIFU: [chuckles] Okay, so, let's quickly move on. And we're going to talk about fingerprints, common misconceptions, pet peeves, and other random pearls of knowledge. So Scott, why don't you kick things off with the fingerprints?
DR. STERN: Okay, so it's not really a fingerprint because it's not a physical exam finding, but nonetheless, a ferritin of less than 15 really suggests iron deficiency, with a likelihood ratio of 51, so just shockingly high.
DR. CIFU: Right. So ferritins can be high, right? Even with iron deficiency if there is inflammation going on, but a low ferritin is really powerful. My fingerprint which is a true fingerprint, a physical exam finding is conjunctival pallor. If it's there, it really suggest anemia anemia and the positive likelihood ratio for conjunctival pallor is 16.7, and a pale palmar crease is about 8.
DR. CIFU: And I would actually just tell people, if you Google conjunctival pallor, you see these fabulous pictures of people who have conjunctival pallor and you can really see what that means.
DR. STERN: I was going to say the same thing, because it's the red rim at the edge. And so if you don't know what you're looking for with that, you really won't get it. But sometimes you see the slate-gray conjunctiva, and you're like, oh my God. Right? We're going to go into common misconceptions next. And the one that I was going to do ties right into what you've just said, which is the reason you have to look at conjunctival pallor is because skin color is essentially worthless.
DR. STERN: I mean, everybody has different tones, and an Irish person is always going to look more pale essentially than an African American person. And it really doesn't help. And so, I think we have a bad habit of kind of looking at the skin and saying, you don't look anemic and that's really dumb.
DR. CIFU: I've missed a lot of anemia just looking at people's faces. But I have to say, yesterday I saw a guy and I walked in and I was like, that guy's anemic, because it's someone I knew and I mean he looked pale comparatively.
DR. STERN: How low was his hemoglobin?
DR. CIFU: He was 6.2.
DR. STERN: Wow.
DR. CIFU: That's right.
DR. STERN: He was pretty anemic.
DR. CIFU: So my common misconception is a little bit restating, is-- The misconception would be that iron deficiency has to be microcytic, B12 deficiency has to be macrocytic and that's just not true. And I actually pulled some of the data here that's pretty remarkable. So 12% of patients who have B12 deficiency are microcytic, while 17% are normocytic. So putting those together, you're basically taking a third of B12 deficient people who are not macrocytic.
DR. CIFU: And on the other hand, if you look at people with iron deficiency, been lots of studies looking at this, only about 85 to 90% of those people are microcytic. So there are certainly people with iron deficiency who are not microcytic, often that's because there are other deficiencies as well.
DR. STERN: Right. And as you know, the more severe the iron deficiency is, and chronic, typically the lower the MCV gets, but, you still want to catch early iron deficiency, right? Because it could be a tumor that's bleeding.
DR. CIFU: And MCV should not be your screening test basically.
DR. STERN: Right.
DR. CIFU: Let's go into our favorite pet peeves. What have you got for me?
DR. STERN: Well, I've already said it. I think you've got to look for the cause of anemia. Anemia is not a diagnosis. And the number of people I've seen over the years who would have been horribly managed, had we not looked for their cause of anemia would be just unbelievable.
DR. CIFU: It's a little bit of foreshadowing, right? It's like delirium, delirium is not a diagnosis. It's a symptom and you got to figure out what's underlying that--
DR. STERN: Are you going to be presenting me with delirium?
DR. CIFU: I'm going to be killing you--
DR. STERN: I'm really afraid now what you're going to do with that, okay.
DR. CIFU: So, my pet peeve is seeing macrocytic anemia and saying, oh, B12 or folate deficiency. So A. these days it's never folate deficiency, right? There's so much folic acid, folate in everything, that I haven't seen someone with primary folate deficiency in you know, a decade. Yes, B12 deficiency is common. B12 deficiency is actually more common as you take care of older people who often have atrophic gastritis, often are on PPIs, but there are lots of other things and they're interesting.
DR. CIFU: So alcohol use causes a macrocytic anemia, often looking at the patient's platelets and LFTs will tip you off there. Hypothyroidism, usually not something which is really going to fool you, because people have to be really hypothyroid. Medications, methotrexate, Dilantin, absolutely, absolutely cause macrocytic anemia. Back in the day, AZT was a big one, I don't think anybody ever uses AZT anymore.
DR. CIFU: And then just liver disease and we've mentioned before, actually having a lot of reticulocytes can cause macrocytosis, though not huge macrocytosis, but certainly an MCV of 103, 105, something like that. Last section we always do is clinical pearls. What kind of gems can you leave us with?
DR. STERN: Well, we've kind of gone over them actually over the course of this, I guess the first one, I would say again, just remember to get your retic count because it's sometimes very helpful.
DR. CIFU: And I would say this is maybe just a little bit of helping people to cheat while they're on the wards, is come up with some really good uncommon causes of anemia to sort of spice up your differentials. The reality is, most anemia you find will be easily explained by, I don't know, iron deficiency, anemia of chronic disease, B12 deficiency, and malignancies.
DR. STERN: Right, totally.
DR. CIFU: I think that's sort of everything. But there's some cool ones, right? So, a low copper level, or a high zinc level, can actually cause microcytic anemia, might be fun to just throw it in your differential and a diagnosis that I always remember, pure red cell aplasia, which is almost like a pancytopenia, which is only affecting the red cell line, can cause a normocytic anemia. And one of my dear friends and Co. medical students, nailed this diagnosis on a neurology service as a third year medical student, and the entire team was in awe of her.
DR. CIFU: So I remember just because of that.
DR. STERN: We saw actually on the floors, I didn't see the person, someone else saw them, a guy who was severely anemic from copper deficiency, and it turned out what he'd been doing is, when that article came out years ago about zinc stopping the common cold or treating it, he took zinc everyday for a year and the zinc had chelated his copper. So he had virtually no copper in his body, and was profoundly anemic because of that.
DR. CIFU: That's interesting. On the other hand, they say you can get high copper, from drinking Moscow mules because you're supposed to drink in copper cups, and the vodka leaches the copper.
DR. STERN: So does that mean that we should take zinc every day to prevent the cold and then drink-- what was that? What am I going to drink with this?
DR. CIFU: You wash your zinc down with vodka in the copper cup.
DR. STERN: Oh there we go, okay. That sounds like a great idea.
DR. CIFU: I think, am I up? I think I'm up.
DR. STERN: All right, good, no, you just did the zinc and the copper.
DR. CIFU: That's right.
DR. STERN: I was just going to say what we've already said. Iron deficiency requires an explanation. Boy, if you don't do that, you just sign the check to the lawyers and they get to fill in the zeros.
DR. CIFU: And you should pay us if you miss that, because I think we've covered that on GI bleeding.
DR. STERN: [chuckles]
DR. CIFU: You guys should know that. My next one is, here's a weird pearl but, sickle cell anemia is interesting. I have never been on service, but I think I've never been on the general medicine service anywhere I'm not taking care of someone with a vaso-occlusive crisis. And I always, always, always take my team through all the complications of sickle cell disease. And you can start with the brain, and go all the way down to the toe, and basically go through how sickle cell disease affects every organ in the body.
DR. CIFU: It's an amazingly interesting disease. I think sickle cell was actually designed by some intelligent being to enable people to get the worst care in our healthcare system because it generally affects people who are underrepresented among the doctors who are taking care of them, it's a subject of pain complaint, there's also issues about pain control.
DR. CIFU: And so often, as doctors we kind of blow it off almost, we don't give it quite enough respect. And so making sickle cell something interesting that you can talk about can get you more engaged in it, and hopefully do a better job taking care of the patients.
DR. STERN: I saw a really interesting thing on a sickle cell patient as a third year medical student. So this is about 1870 or something like that. And I meant 1870. [chuckles] The guy was having a vaso-occlusive crisis and he was jaundiced a bit more than you typically see. And he was using a urinal in his room, and the urine was dark, and everybody was attributing his jaundice to a sickle cell disease but of course you don't get bilirubinuria with hemolysis, right?
DR. STERN: So he had stones obstructing his common bile duct from his hemolysis and his bilirubin stones actually.
DR. CIFU: And so we don't get emails, I'll have to call you on that you should be using patient first language, and say the person with sickle cell disease and not a sickle cell patient, I think it's what you said.
DR. STERN: Ah, okay, well I'm old. [chuckles]
DR. CIFU: I think we might be done. Do you have anything further or are we all finished?
DR. STERN: No, that's all I've got.
DR. CIFU: Okay. We hope you found this episode of the Symptom to Diagnosis podcast useful and a bit enjoyable. A reminder that the cases that we discuss are drawn from our clinical experiences but, because protecting patient privacy is part of our oath, we never discuss actual patients and most cases are composites. As a reminder, our textbook "Symptom to Diagnosis: An Evidence-Based Guide" takes a much deeper dive into how to think about and reason through the diagnosis of medical presentations.
DR. CIFU: The book's available in print, on your handheld device, and in a new fully searchable mode via the Access Medicine website, available worldwide from McGraw Hill. The music for this, the S2D Podcast is courtesy of Dr. Maylyn Martinez.
Segment:0 .
DR. CIFU: I'm Adam Cifu.
DR. STERN: And I'm Scott Stern.
DR. CIFU: And we're back with episode 9 of the Symptom to Diagnosis podcast. For those of you who've been with us this far, you must be sick of the podcast introduction. So Scott, let's just jump right into it. Our case this week is anemia, which I always think is the problem with the most classic internal medicine differential diagnosis, right?
DR. STERN: Right totally.
DR. CIFU: So you're the expert of the day.
DR. STERN: I like that.
DR. CIFU: You got new glasses.
DR. STERN: Well, reading glasses, they have lights on them, so I can really see in the dark. Anyway--
DR. CIFU: Well, that's the nerdiest thing I've ever seen.
DR. STERN: [laughing] Thank you.
DR. CIFU: Anyway, so you're the expert of the day, you want to present a case today?
DR. STERN: I do, and I'm going to stump you on this one. I'm just giving you a warning. [chuckles] This will be fun when you're squirming. Anyway, I saw a 65-year-old man many years ago now, who had self-diagnosed sciatica, and he actually went to the emergency room because the pain was so bad that he couldn't get any relief. And believe it or not, he was actually admitted for evaluation and treatment because he was in so much pain, which as you know is really bizarre.
DR. STERN: He noted severe pain radiating down his left leg for the last month. He tried Advil, Tylenol, gabapentin, physical therapy and nothing was giving him any relief. And his pain was 9 out of 10, waking him up at night, it was really awful. On admission he had some labs, and they included a CMP that was unremarkable. His CBC revealed a hematocrit of 28, and his hemoglobin was 9.
DR. STERN: So, that's the case.
DR. CIFU: That's all? You're kidding me?
DR. STERN: That's it, you're on your own.
DR. CIFU: Okay so, you're keeping a lot of the things that I was hoping for away. But I guess maybe I'll frame it in that, if I'm walking in to see this guy, what strikes me is 65-year-old guy, not only anemia but back pain, which he's calling sciatica, but whatever, we'll just take it as back pain. So, I guess the things that would go through my mind at this point would be some bad things, I would think about what could cause anemia and back pain.
DR. CIFU: I guess I'd think about malignancies, could this guy have prostate cancer with metastasis to his spine? Could he have myeloma? Right? With maybe a compression fracture? I guess I didn't quite get the acuity of this all, but maybe if I go crazy and say, it's acute, could this be an infection? And the guy has got infection like, I don't know, spinal osteodiscitis, even bacterial endocarditis, right?
DR. CIFU: Maybe that's causing an anemia of inflammation. I guess the back pain could be sort of true, true, and unrelated, and the guy could just have your basic iron deficiency anemia or B12 deficiency. Maybe that's sort of what I'm thinking. I guess, my next steps-- I'd obviously examine the guy, I'd see if he had tenderness in his back.
DR. CIFU: Maybe flank tenderness, does the guy have an obstruction and has the anemia because of chronic renal insuffiency, because of obstruction, that's probably a bit of a stretch, but I'm lost here. And then where I always start, I'd say, I'd like to see his retic because I want to know, is this underproduction or not? I'd want his MCV to help frame the differential for me. And you're particularly cruel by actually only giving me a hemoglobin.
DR. CIFU: So I'd certainly also want to see his white count, his platelets, is this pancytopenia or not? And I'd like to see a smear which often doesn't help, but sometimes it really helps. So maybe that's what I have to say.
DR. STERN: Well, that's great, I just want to point out one thing that you've done automatically, which was really critical in this case, which you say, he not only has back and leg pain, but he has anemia. And oftentimes in the hospital, you know what happens is so many people are anemic that the anemia is ignored. Oh well, they're just anemic, because everybody's anemic. But he doesn't really have a history that suggests he should be anemic.
DR. STERN: And what you're taking for granted, is you're immediately trying to put those together. And actually, the house staff that was seeing him at the time had completely ignored his hematocrit and were solely focused on his back pain.
DR. CIFU: It's interesting, I think the problem with that is that we all learn Ockham's razor, right? The whole idea, parsimony, try to figure one diagnosis that covers everything. Though, people also toss around Hickam's dictum, right? That you can have as many diagnosis as you damn well please. And often in the hospital, people have so many diagnoses that there's less of an incentive to actually come up with one unifying diagnosis.
DR. STERN: Well that, and anemia is so common, because so many people are so sick in the hospital, that it's almost taken for granted, that everybody in the hospital is anemic. But this is a guy who was otherwise well before, and is now clearly anemic. And if you don't dive into that, and you don't figure that out, then for sure you're missing something with this--
DR. CIFU: Totally, totally, good point.
DR. STERN: So, I think now maybe what we'll do is take a deep dive into anemia and then come back to the case, or would you like some more data first?
DR. CIFU: No, no, let's do that. So usually at this point what we do is you give us five points, and I just try to say smart things as you go through.
DR. STERN: Okay well, good luck with that one. So, my first point you've actually already stolen from me, but I'll repeat it, which is, it's always important when you think about someone who's anemic, to look at the smear, as well as the white blood count and the platelet count, in addition to the hemoglobin, because sometimes you get critical clues. I mean, obviously a smear can sometimes show you schistocytes or sickle cells, which can help make the diagnosis of either hemolytic process or sickle cell anemia.
DR. STERN: And also the white blood count and the platelet count can sometimes be very revealing. I told you about a patient, another patient I saw recently, who I got a stat lab called for, 65-year-old guy who came in feeling kind of tired, nothing else specifically and I got a CBC just to see, and at like nine o'clock at night, the lab called me and said his white blood count was 6.2. It's an emergent value.
DR. STERN: And of course the most--
DR. CIFU: His hemoglobin.
DR. STERN: His hemoglobin thank you, was 6.2 and the immediate knee jerk response it's probably another guy with iron deficiency anemia and colon cancer. But actually because, I've given this lecture many times, I immediately asked the lab for his white blood count, and his platelet count. I said, hang on for a second, so I went back to check, and his white blood count was 2, with an absolute neutrophil count of only 420, and his platelet count was 129,000.
DR. CIFU: Wow.
DR. STERN: So this isn't anemia, this is then pancytopenia which has a completely different differential, and you always of course worry about leukemias in that situation and indeed, this was his presentation of AML. So, first point is, look for pancytopenia first.
DR. CIFU: Your question about the white cell count was good because, A. it helped the patient and B. you would have just gotten another call like 20 minutes--
DR. STERN: [chuckles] It's totally fine, they would have been waking me up again, you know.
DR. CIFU: Okay, so that's point one, what's point two?
DR. STERN: And you said this as well, and the second key point is to look at the reticulocyte count, I just want to emphasize that. Probably I would guess that 90% of the patients that we see in the hospital and outside of the hospital who have anemia have an underproduction anemia, the most common ones being iron deficiency, and anemia of chronic disease. But, every now and then, maybe 5-10% of patients have hemolysis and the real clue to that is often going to be that the reticulocyte count is high.
DR. STERN: It's often not evident on the smear, and all those causes whether it's TTP or G6PD deficiency, or autoimmune hemolytic anemia, you're never going to make that diagnosis, if you don't get that reticulocyte count, so that's next.
DR. CIFU: They always talk about these days kind of systematic solutions to errors. Do you think that a reticulocyte count should be automatic with a CBC, or maybe at least the CBC with diff?
DR. STERN: Well, I think it should be triggered by the anemia. So, maybe what they could do is have an automatic reflex response like we do for HIV tests, do a follow-up, that if the person's anemic, you get a retic.
DR. CIFU: Right so, if the person's anemic and their last CBC was not anemic there's a retic--
DR. STERN: Exactly and that's a good point to add because so many people are chronically anemic you might not want to do it each time.
DR. CIFU: I think that'll be helpful.
DR. STERN: Yeah.
DR. CIFU: Okay, those are two great points, what's your number three?
DR. STERN: Well, the third one is again, you mentioned this, so you did very well, I'm very proud of you. And that was the MCV is a good guidepost, but not a hard and fast rule. Obviously macrocytosis suggests, but doesn't confirm B12 and folic acid deficiency, and other forms of macrocytosis and microcytosis can suggest iron deficiency, thalassaemia, chronic disease, but there is considerable overlap.
DR. STERN: But the MCV certainly gives you an important clue and that will be next.
DR. CIFU: Great. I'm going to maybe blow one of my points that I was going to use later in this, but I always say that the MCV is incredibly good at organizing your differential diagnosis, but it is not a diagnostic test.
DR. STERN: Yeah, I mean, it's definitely-- at least a lot of diagnostic error, right?
DR. CIFU: I agree.
DR. STERN: We'll come back to that.
DR. CIFU: Point four?
DR. STERN: Point four is iron deficiency is not a final diagnosis, you have to find the cause. Now in the world, the most common causes are obviously, women of childbearing years whose iron-- and in other parts of the world it's iron deficiency due to diet, but in the West, especially in post-menopausal women and in men, it requires an explanation. And it's often, as you know, due to occult bleeding from a colon cancer, or stomach cancer and so on.
DR. STERN: And so, if you stop the workup in someone who has iron deficiency anemia, who's a post-menopausal woman or a man, you've really committed malpractice.
DR. CIFU: I actually like things like that. This is on the order of, you know, older person comes into my office with dysphasia, when there are things like, "That's great, I don't have to think about this one." You're an older person, iron deficiency anemia. Okay, you know, I got a skimpy, I got to figure this out. You come in and you tell me that food's getting stuck in your throat. Whatever, you can keep talking, but I know what I'll do.
DR. STERN: And in a way that does make practice easier because when you understand that these are just hard and fast rules, you don't worry about it. You just do what needs to be done.
DR. CIFU: And then you kind of start thinking, after the endoscopy's--
DR. STERN: Right, right, exactly, that's the way it goes.
DR. CIFU: Okay, and number five, bring us home.
DR. STERN: The last point is in chronic disease you need to find the cause. It's not okay to say somebody has the anemia of chronic disease when you don't get what that is. I mean, well controlled hypertension for instance, without renal insufficiency doesn't cause the anemia of inflammation and so on. And so if you don't have a cause, then it's a clue that something else is wrong, and to ignore that clue is really missing the boat.
DR. CIFU: And I think it's one of the reasons that we've gone from calling it anemia of chronic disease to anemia of chronic inflammation, because you need an inflammatory cause. But the hard part is then also, so many of our patients have so many problems, and you're like, "Do these account for it or not?" And, and it is one of the places that the kind of secondary tests of anemia, you know, iron studies and such, are often not really diagnostic.
DR. STERN: Well, where I find it helpful is when you don't know that something's wrong with someone and you get a CBC and you're wondering, is this really real? Is it partly somatic? How sick is this person? And then you find out they're anemic, and the person who you thought was well, and you say, you do the workup and it looks like anemia of chronic inflammation and you don't have an explanation, you know the dig.
DR. CIFU: Right. Good point. Okay, I actually dread saying this in this case, but let's get back to that ridiculous case that you presented to me.
DR. STERN: All right, so would you like--
DR. CIFU: I'd like to have a physical exam.
DR. STERN: Yeah, so his physical exam was pretty unremarkable. He was afebrile which is obviously important given some of the things you mentioned. His heart and lung and abdominal exams are unremarkable. Interestingly enough, his back was non-tender, his straight leg raise was negative, his strength was all intact. And just to emphasize, his pain he was calling sciatica, but his pain was really in his leg, up and down his leg.
DR. CIFU: Interesting. So hearing that, I guess I would ask you, did you really listen to this guy's heart? Did you make sure he didn't have a murmur?
DR. STERN: I did. I always do that and you know that, I have an electronic stethoscope that even given my old age, I can amplify this out, so yes I did.
DR. CIFU: And his leg exam, it sounds like, and tell me if I'm right, that it was pain that he was feeling, but you were actually not able to reproduce that on exam.
DR. STERN: Correct.
DR. CIFU: Huh! So, I guess the things that I think about then, I'd be considering, a marrow process, right? There are some people who, when they have a super hyperactive marrow actually get that kind of deep bone pain, this is pretty localized for that which makes me feel a little bit uncomfortable with that. I have certainly in my day seen people with pathologic fractures actually, where I can't induce anything, but their bone is just such a mess underneath that that's the problem.
DR. CIFU: And given that this is localized, yeah again, I mean, metastatic cancer, myeloma with plasmacytoma, those are all possible, but I got to see some labs here.
DR. STERN: So as I said, his comprehensive metabolic panel was normal. The residents - because the patient had come in with a self-diagnosis of sciatica - did an MRI, and it was kind of interesting, their thinking. So, they did an MRI, it was normal.
DR. CIFU: This is going to-- Oh, it was normal, okay.
DR. STERN: Normal.
DR. CIFU: I thought I was going to say, is going to piss me off because they made the diagnosis with the wrong test without thinking. But I'm happy it was normal.
DR. STERN: No, so it was really fascinating. So the MRI was normal, and I said, "So what do you think is going on?" And they said, "Well, we think it's sciatica." And I said, "Well, I don't really understand that. You've not shown anything compressing the nerve. And you're sticking with that diagnosis." And they said, "Well, maybe the MRI is normal, because it's just an error." And I'm like, "Well, how sensitive is the MRI?" And as you know, for a herniated disc it's exquisitely sensitive.
DR. STERN: And so they said," Well, maybe it's just missing." Then I asked them, "Why is he anemic then?" And they're like, "We don't know." But they were comfortable saying they didn't know repeatedly and I was not comfortable with saying they didn't know repeatedly.
DR. CIFU: And I assume this MRI was of the LS spine.
DR. STERN: Correct, that's right.
DR. CIFU: So it's conceivable that maybe there is something to see, but they're just imaging the wrong place. I've had this conversation a lot over my career when people order a test, it doesn't show them what they want and so then they ignore the result. And it's interesting because often you say, so why did you order that test in the first place? And it's not really the ordering the test that's the problem, it's the reaction to it.
DR. STERN: Right.
DR. CIFU: Because in fact, with some tests if your pre-test probability is really high, and the test is negative, you should still believe the diagnosis, but your next step should be, I got to do something else, not "Okay, we're done here."
DR. STERN: Right and the other clue, I mean, not only would it be unlikely with the MRI being so sensitive, but there's another phenomenon, his anemia that they haven't explained, and you put those two things together and it's like, okay, something's wrong. That's a lot of anchoring bias. I think it's just worth pointing that out, right?
DR. CIFU: Okay, I still want MCV, retics. I don't know... PSA, SPEP, UPEP.
DR. STERN: Okay.
DR. CIFU: Blood cultures, CRP.
DR. STERN: All right, so let's go through it. So the CBC, the white count and the platelet count were normal, so it was not pancytopenia. And as you know, the next step was the retic count, which was low, his reticulocyte production index which is the eaiest way to decide whether it's underproduction, or overproduction was 1 which is suggestive of an underproduction anemia. His MCV was 85.
DR. CIFU: So let me just say, so we've worked through that nicely and this is the way it's laid out actually in the Symptom to Diagnosis textbook is, pancytopenia or no? And actually, I think it's not just pancytopenia is this pancytopenia, or is this hemoglobin and platelets which you'll sometimes see in destruction, right? So then we move on to, is this underproduction? And we find out that this is underproduction. And so this is where classically you'd get into is this microcytic, normocytic, macrocytic, and of course, since you're here to torture me, you're going to give me a normocytic.
DR. STERN: Of course I am, so his MCV was 85.
DR. CIFU: Which essentially helps me in no way whatsoever, and then I guess the other things where I would go next, honestly-- This is acute or subacute? Or like how long--
DR. STERN: The pain is about a month.
DR. CIFU: About a month. So I would send blood cultures, though I really think that's not going to tell me anything. I would do my PSA, SPEP and UPEP though to be honest with you, with a normal alk phos on that CMP with normal renal function, I think that's unlikely to show me anything, and I'd want some sort of imaging of that leg, whatever. I'd probably just start with an X-ray.
DR. STERN: So several things you did, I really like, which is-- I'm just going to emphasize them. You went to the MCV at the end of that series of steps. I see many people jump to MCV without having looked at the retic again and not looking at the full CBC, so that's great.
DR. CIFU: And that can really scr** you up because a high retic count-- this can actually give you macrocytosis, but just because their retics are being worked into it that's not telling you anything.
DR. STERN: Right. So that's terrific. The alk phos won't necessarily be elevated in myeloma, but the SPEP and the UPEP might be, so they were normal. And finally, what we did was what you recommended, which was imaging of the leg. And actually, I don't remember the sequence of events, but we actually got a bone scan first because we were stymied. And that showed multiple areas of high intensity throughout the bones in the leg, consistent with?
DR. CIFU: Paget's disease? [chuckles]
DR. STERN: No, so we took him to biopsy, and he had metastatic adenocarcinoma of unclear primary.
DR. CIFU: You suck.
DR. STERN: [chuckles] I told you it was hard.
DR. CIFU: That's a terrible case but really interesting. And so his anemia, I would really take that, to be sort of anemia of chronic inflammation, right? That the guy's systemically ill, probably chronically ill. And it has nothing to do with bone marrow invasion, just that he's sick otherwise.
DR. STERN: Right, exactly. But the reason I thought it was worth presenting the case, is it was really his anemia that was one thing that led us to say, we need to keep digging. And I thought that was really interesting.
DR. CIFU: Actually the real reason you presented the case was to make me look bad on our podcast. I will get back--
DR. STERN: [chuckles] I know I'm a little bit-- That thought's already crossed my mind. I might not show up for the next one.
DR. CIFU: [chuckles] Okay, so, let's quickly move on. And we're going to talk about fingerprints, common misconceptions, pet peeves, and other random pearls of knowledge. So Scott, why don't you kick things off with the fingerprints?
DR. STERN: Okay, so it's not really a fingerprint because it's not a physical exam finding, but nonetheless, a ferritin of less than 15 really suggests iron deficiency, with a likelihood ratio of 51, so just shockingly high.
DR. CIFU: Right. So ferritins can be high, right? Even with iron deficiency if there is inflammation going on, but a low ferritin is really powerful. My fingerprint which is a true fingerprint, a physical exam finding is conjunctival pallor. If it's there, it really suggest anemia anemia and the positive likelihood ratio for conjunctival pallor is 16.7, and a pale palmar crease is about 8.
DR. CIFU: And I would actually just tell people, if you Google conjunctival pallor, you see these fabulous pictures of people who have conjunctival pallor and you can really see what that means.
DR. STERN: I was going to say the same thing, because it's the red rim at the edge. And so if you don't know what you're looking for with that, you really won't get it. But sometimes you see the slate-gray conjunctiva, and you're like, oh my God. Right? We're going to go into common misconceptions next. And the one that I was going to do ties right into what you've just said, which is the reason you have to look at conjunctival pallor is because skin color is essentially worthless.
DR. STERN: I mean, everybody has different tones, and an Irish person is always going to look more pale essentially than an African American person. And it really doesn't help. And so, I think we have a bad habit of kind of looking at the skin and saying, you don't look anemic and that's really dumb.
DR. CIFU: I've missed a lot of anemia just looking at people's faces. But I have to say, yesterday I saw a guy and I walked in and I was like, that guy's anemic, because it's someone I knew and I mean he looked pale comparatively.
DR. STERN: How low was his hemoglobin?
DR. CIFU: He was 6.2.
DR. STERN: Wow.
DR. CIFU: That's right.
DR. STERN: He was pretty anemic.
DR. CIFU: So my common misconception is a little bit restating, is-- The misconception would be that iron deficiency has to be microcytic, B12 deficiency has to be macrocytic and that's just not true. And I actually pulled some of the data here that's pretty remarkable. So 12% of patients who have B12 deficiency are microcytic, while 17% are normocytic. So putting those together, you're basically taking a third of B12 deficient people who are not macrocytic.
DR. CIFU: And on the other hand, if you look at people with iron deficiency, been lots of studies looking at this, only about 85 to 90% of those people are microcytic. So there are certainly people with iron deficiency who are not microcytic, often that's because there are other deficiencies as well.
DR. STERN: Right. And as you know, the more severe the iron deficiency is, and chronic, typically the lower the MCV gets, but, you still want to catch early iron deficiency, right? Because it could be a tumor that's bleeding.
DR. CIFU: And MCV should not be your screening test basically.
DR. STERN: Right.
DR. CIFU: Let's go into our favorite pet peeves. What have you got for me?
DR. STERN: Well, I've already said it. I think you've got to look for the cause of anemia. Anemia is not a diagnosis. And the number of people I've seen over the years who would have been horribly managed, had we not looked for their cause of anemia would be just unbelievable.
DR. CIFU: It's a little bit of foreshadowing, right? It's like delirium, delirium is not a diagnosis. It's a symptom and you got to figure out what's underlying that--
DR. STERN: Are you going to be presenting me with delirium?
DR. CIFU: I'm going to be killing you--
DR. STERN: I'm really afraid now what you're going to do with that, okay.
DR. CIFU: So, my pet peeve is seeing macrocytic anemia and saying, oh, B12 or folate deficiency. So A. these days it's never folate deficiency, right? There's so much folic acid, folate in everything, that I haven't seen someone with primary folate deficiency in you know, a decade. Yes, B12 deficiency is common. B12 deficiency is actually more common as you take care of older people who often have atrophic gastritis, often are on PPIs, but there are lots of other things and they're interesting.
DR. CIFU: So alcohol use causes a macrocytic anemia, often looking at the patient's platelets and LFTs will tip you off there. Hypothyroidism, usually not something which is really going to fool you, because people have to be really hypothyroid. Medications, methotrexate, Dilantin, absolutely, absolutely cause macrocytic anemia. Back in the day, AZT was a big one, I don't think anybody ever uses AZT anymore.
DR. CIFU: And then just liver disease and we've mentioned before, actually having a lot of reticulocytes can cause macrocytosis, though not huge macrocytosis, but certainly an MCV of 103, 105, something like that. Last section we always do is clinical pearls. What kind of gems can you leave us with?
DR. STERN: Well, we've kind of gone over them actually over the course of this, I guess the first one, I would say again, just remember to get your retic count because it's sometimes very helpful.
DR. CIFU: And I would say this is maybe just a little bit of helping people to cheat while they're on the wards, is come up with some really good uncommon causes of anemia to sort of spice up your differentials. The reality is, most anemia you find will be easily explained by, I don't know, iron deficiency, anemia of chronic disease, B12 deficiency, and malignancies.
DR. STERN: Right, totally.
DR. CIFU: I think that's sort of everything. But there's some cool ones, right? So, a low copper level, or a high zinc level, can actually cause microcytic anemia, might be fun to just throw it in your differential and a diagnosis that I always remember, pure red cell aplasia, which is almost like a pancytopenia, which is only affecting the red cell line, can cause a normocytic anemia. And one of my dear friends and Co. medical students, nailed this diagnosis on a neurology service as a third year medical student, and the entire team was in awe of her.
DR. CIFU: So I remember just because of that.
DR. STERN: We saw actually on the floors, I didn't see the person, someone else saw them, a guy who was severely anemic from copper deficiency, and it turned out what he'd been doing is, when that article came out years ago about zinc stopping the common cold or treating it, he took zinc everyday for a year and the zinc had chelated his copper. So he had virtually no copper in his body, and was profoundly anemic because of that.
DR. CIFU: That's interesting. On the other hand, they say you can get high copper, from drinking Moscow mules because you're supposed to drink in copper cups, and the vodka leaches the copper.
DR. STERN: So does that mean that we should take zinc every day to prevent the cold and then drink-- what was that? What am I going to drink with this?
DR. CIFU: You wash your zinc down with vodka in the copper cup.
DR. STERN: Oh there we go, okay. That sounds like a great idea.
DR. CIFU: I think, am I up? I think I'm up.
DR. STERN: All right, good, no, you just did the zinc and the copper.
DR. CIFU: That's right.
DR. STERN: I was just going to say what we've already said. Iron deficiency requires an explanation. Boy, if you don't do that, you just sign the check to the lawyers and they get to fill in the zeros.
DR. CIFU: And you should pay us if you miss that, because I think we've covered that on GI bleeding.
DR. STERN: [chuckles]
DR. CIFU: You guys should know that. My next one is, here's a weird pearl but, sickle cell anemia is interesting. I have never been on service, but I think I've never been on the general medicine service anywhere I'm not taking care of someone with a vaso-occlusive crisis. And I always, always, always take my team through all the complications of sickle cell disease. And you can start with the brain, and go all the way down to the toe, and basically go through how sickle cell disease affects every organ in the body.
DR. CIFU: It's an amazingly interesting disease. I think sickle cell was actually designed by some intelligent being to enable people to get the worst care in our healthcare system because it generally affects people who are underrepresented among the doctors who are taking care of them, it's a subject of pain complaint, there's also issues about pain control.
DR. CIFU: And so often, as doctors we kind of blow it off almost, we don't give it quite enough respect. And so making sickle cell something interesting that you can talk about can get you more engaged in it, and hopefully do a better job taking care of the patients.
DR. STERN: I saw a really interesting thing on a sickle cell patient as a third year medical student. So this is about 1870 or something like that. And I meant 1870. [chuckles] The guy was having a vaso-occlusive crisis and he was jaundiced a bit more than you typically see. And he was using a urinal in his room, and the urine was dark, and everybody was attributing his jaundice to a sickle cell disease but of course you don't get bilirubinuria with hemolysis, right?
DR. STERN: So he had stones obstructing his common bile duct from his hemolysis and his bilirubin stones actually.
DR. CIFU: And so we don't get emails, I'll have to call you on that you should be using patient first language, and say the person with sickle cell disease and not a sickle cell patient, I think it's what you said.
DR. STERN: Ah, okay, well I'm old. [chuckles]
DR. CIFU: I think we might be done. Do you have anything further or are we all finished?
DR. STERN: No, that's all I've got.
DR. CIFU: Okay. We hope you found this episode of the Symptom to Diagnosis podcast useful and a bit enjoyable. A reminder that the cases that we discuss are drawn from our clinical experiences but, because protecting patient privacy is part of our oath, we never discuss actual patients and most cases are composites. As a reminder, our textbook "Symptom to Diagnosis: An Evidence-Based Guide" takes a much deeper dive into how to think about and reason through the diagnosis of medical presentations.
DR. CIFU: The book's available in print, on your handheld device, and in a new fully searchable mode via the Access Medicine website, available worldwide from McGraw Hill. The music for this, the S2D Podcast is courtesy of Dr. Maylyn Martinez.
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