Transcript: Leukocytosis Case Study: Lab Interpretation for New Grad NPs

​Liz Rohr:

Hey there, it's Liz Rohr from Real World NP and you're watching NP Practice Made Simple, the weekly videos to help save you time, frustration, and help you learn faster so you can take the best care of your patients. Today I'm going to be talking to you about high white blood cell counts, and these can be a little bit intimidating, a little bit scary, but I've actually broken it down to make it really easy. I think you're going to feel a lot better after watching this presentation. I'm going to be using a case study and I'm really going to break it down so you'll know when you can kind of monitor those patients, just watch and wait and see kind of thing, versus when do you work them up further, when you send them to hematology oncology, versus when do you send to the ER?

And I also did this in collaboration with a hematologist oncologist, which was super fun. But also kind of just gives you that backup reassurance that this is my primary care perspective, and not everything that you see about lab interpretation comes from a hard, concrete guideline, but it's kind of a gist of practice that everyone operates by. So this is not just me, this is in collaboration with HemOnc and with other specialists and internal medicine physicians and nurse practitioners that I've worked with before. So I hope you enjoy this video, and without further ado, I'm going to share my screen with you.

High white blood cell, leukocytosis. This isn't Luis, this is not his real name or his photo. He's 50, he's reestablishing care with a new PCP, and he also has a complaint of abdominal pain. This patient, I care for him currently. But this presenting case was back when he first came to the clinic from a different provider who's not here anymore. This is his visit way back then. He complained of abdominal pain within abdominal wall hernia on and off for the last year. He had a lipoma biopsied in the past and was told he needed a surgery for his hernia. He has a former 30-pack year history smoker and he quit 12 years ago, luckily. He doesn't drink alcohol or use other drugs. He has a past medical history of high cholesterol, obesity and has lost some weight.

And it was kind of unclear from the note. I think he intentionally was losing weight, but that was definitely a note there. A family history of stroke and diabetes and high blood pressure. No past surgical history, no medications. And his blood pressure today is 130/86, heart rate of 80. BMI is 29 and he has a normal temperature and oxygen. The ROS, I'm going to go into the ROS and the physical exam because he also has a problem based complaint. It was negative for fever, chills, weakness, respiratory, cardiac symptoms, nausea, vomiting, constipation, diarrhea, changes in his stool. I didn't write this down, but he also had no urinary symptoms as well, genital urinary, which is important when you're assessing somebody with abdominal pain. He has a normal HEENT exam, respiratory, cardiovascular. Neuro, and psych I always make a note about, because it gives some good context in terms of the other physical complaints that you're looking at.

For abdomen exam, he has a ventral hernia, which is reduceable, and it's only with straining. And he doesn't have any guarding, rebound, tenderness or hepatosplenomegaly. I'm going to make a note about that at the end to talk about hernia, so just pause for a second. Today I'm going to focus on labs, I'm going to touch on the other components of holistic care at the end. His labs I'm going to check today are a CBC, CMP, hemoglobin A1C, based on screening guidelines, cholesterol based on screening guidelines. And I couldn't help myself, but I threw in that she did do a general surgical consult at this appointment. Here are the lab results. Before I get into the results down here, the a complete metabolic panel was normal. The hemoglobin A1C and the cholesterol is normal. On here I've got a CBC with a differential, and I'm just going to jump over the white blood cell count of 74.

The normal is 4 to 10, 4 to 11, depending on the lab results that you're using, in terms of reference ranges. Going back over to the left side here, I've got the hematocrit and hemoglobin, which are slightly lower than normal, 39.8%, and 13.5% for hemoglobin. MCH, MCV platelets, red blood cells, RDW, that's all normal. And then hopping over here again to the white blood cell count, this is the differential down below. And a note about differentials is that majority, it seems like every lab does this a little differently, and this is consensus when I speak with other providers, is that there's an automated first pass of what the machine tells you, in terms of the differential. Sometimes there's also a tech who is looking at the labs under the blood smear, under the microscope. And then there's a verification with a pathologist who is a physician.

In this case, this is the automated differential, and the results here are in percentages, which I'm going to talk about in just a second, but you can either see percentages here, or you may see the absolute counts. Just to start the percentages, the lymphocytes are 66%, which, the normal range is 20% to 40%. Monocytes, basophils, eosinophils and bands are all normal. Neutrophils are very low at six, and sorry that's red, that should be blue because it's low. But neutrophils really should be in the majority of 50% to 70%. And then on this result, it just said other cells up 22%, which is just not normal. And you don't typically see that on your differential unless they're there. Excuse me. Leukocytosis is a high white blood cell count, but it's very non-specific and you need the differential to give you most of the information of what you're looking for.

This should be a major question in your mind. Is this something that's reactive in an active inflammatory process, appropriately so? Meaning that you have something that's some kind of inflammation, whether it's an injury or swelling, or do you have some sort of acute infection? Or is this a bone marrow problem? Bone marrow problems are things like CML, acute leukemias, things like that. And those are the main two areas that you're thinking about, the main questions in your mind when you see a high white blood cell count. There are other kind of artificially raising things to think about, and they actually are not uncommon, especially with the slightly elevated but not super elevated, but something to keep in mind. Here are the steps to leukocytosis workup that I recommend. Do they have symptoms? I was going to start with the next one, which is, how high is it and what type and the peripheral smear?

These actually all work together, these three questions of symptoms, the level of elevation and the type and the peripheral smear, because I just can't talk about them without talking about the other ones. And so I changed this around after practicing this presentation because I couldn't help myself, but this stay with me for a second. So, do they have symptoms? Again, white blood cell count means that it's usually, typically a source of infection. So is it viral, bacterial and acute leukemia, or some other kind of inflammatory process? Do they have chills, fever, any other systemic symptoms? Are their vital signs stable? Do they have fatigue, weight loss, night sweats, those kinds of things? And do they have lymphadenopathy or splenomegaly? A lot of times you're going to do a screening CBC, and you're not necessarily going to be... I mean, that's another topic for another day, how much we should be doing screening CBCs. But regardless, you may not have necessarily known that this was going to happen, and this is kind of more of an incidental finding.

But yeah, these patients, if they're symptomatic, you want to check for angle lymphadenopathy or splenomegaly. And the splenomegaly has to do with, there's a lot of reasons you can have splenomegaly, but in this case, it's referring to when you have high white blood cells, is your spleen over producing those lymphocytes and becoming very enlarged because it's so hyperactive. And that'll kind of give you more clinical clues as to whether or not your white blood cell count being high is a true clinical picture. You also want to look at other symptoms that is presented on their labs, which is anemia, thrombocytopenia, thrombocytosis, because again, that kind of points you in the direction of a bone marrow dysfunction, versus an acute process, because those are all kind of produced simultaneously. And then things like an active arthritis. Not just arthralgia, but the actual physical swelling that you get from a joint swelling can cause a high white blood cell count, things like that.

So how high is it? This is the next question. The normal range is 4,400 to 11,000 cells per microliter, is the unit of measurement. And this is extremely important to correlate clinically, like I just said, talking about any of those symptoms, because that's going to point you down. You want to make sure that somebody isn't having an active infection that you need to treat right now. The kind of not textbook but magic number to keep in your mind is greater than 20 plus with symptoms. Those people are going to need more urgent treatment and evaluation, versus if it's less than 15 to about 20 and they don't have any symptoms. The expert opinion/consensus is to kind of repeat that to see if it hangs on, including your differential and your peripheral smear to kind of look into that a little bit more.

15, I feel comfortable with 15. The hematologist that I was working with to make this presentation was saying 15 to 20-ish. But the most important information is going to be on the next slide, which has to do with what types of white blood cells we're talking about here, and what do they look like? So again, 20 or more with symptoms, absolutely, those people need treatment, versus the less than 15 to 20 could be those kinds of monitor, recheck it, make sure that it's not an artifact, things like that. I'm going to get into that in just a second. If it's greater than 15 to 20 though, greater than 15 or 20, whichever one, I can decide. So for me, I feel comfortable with greater than 15, but you can always...

One note I want to make here, actually, now that I'm talking about this is that, whenever you're unsure, absolutely, you can cold call a hematologist. Meaning that you can pick up the phone, call your local hematologist, the closest one to you. If you're in rural medicine or something like that, just kind of have a conversation with them and be like, "Listen, what do you recommend here? Here are the labs that I have, here are the results, here's what I'm thinking. Is this somebody that you think you should see there? Are there other tests that you recommend to do right now as an outpatient in primary care, versus, do we send them to the ER." And hopefully, you have that clinical judgment there where you can send someone to the ER, but I'll give you some parameters, too. But anyway, those people, if it's persistently above 15 to 20-ish and they don't have symptoms, they need to have that evaluated as well, considering hematology, and as well as that differential with a peripheral smear.

White blood cells greater than 100,000, those people just need to go right to the ER because they're at increased risk for thrombosis, but they also probably have symptoms. You don't usually have a white count of 100 without symptoms. I've never seen it, but that guy got pretty high with his white cell count in the 70s. I'm just going to touch base really broadly, very quickly on the different types of white blood cells, just to kind of bring it back to school. Again, this is super, super broad, so just kind of take it with a grain of salt. But lymphocytes typically viral associated, neutrophils, typically bacterial related. Band, those are those immature neutrophils, and that's what that concept of left shift. So if you have a elevated white blood cell count with your neutrophils and your bands are significantly higher, compared to the other elements, that's not abnormal.

I mean, it's abnormal because it could be an infection, but it's not a cancerous process. But that's what left shift means, is when you have a predominance of bands or bandemia, or whatever. You want to look into, is this a bacterial type of infection? It can be from other causes, but this is, like I said, broad brush, this is the general direction that you're going. Eosinophils, again, broad brush. I'm actually going to do a presentation on somebody with eosinophilia specifically, but this tends to come with allergies, parasites, there's a couple of other things. Monocytes, these are the macrophages, they're the antigen presenting cells. Basophils, this is the smallest amount of white blood cells. And these are kind of like mass cells, they have histamine within them and they attract other cells to the area, they're not macrophages themselves.

But you really don't see as many of the basophils as you do the other portions. This is the other question of, what is the absolute count? So you've looked at if they have symptoms, you've looked at how high it is. Now, what is the absolute count with the differential? And absolute count means, for example, for lymphocytes, we're going to take this for this gentlemen. Lymphocytes is the percentage. Remember going back to that slide? Sorry, I should have copied it on this slide, but going back to the slide of what the percentages were of the breakdown. Using an absolute lymphocyte count calculation, either on MDCalc, which is an app that I recommend in the ultimate resource guide, or you can do a Google as long as it's a reputable site that you're using. Looking at the absolute count, because it doesn't really mean that much.

If your white cell count is 20,000, versus if it's 5, it's going to make a big difference. So there's no threshold for the absolute lymphocyte count, which is considered a true medical emergency. However, if it's greater than 30,000, you'd consider more urgent HemOnc referral, and consider a secondary test called the flow cytometry, which we'll talk about in a second. If it's greater than 5,000, you can repeat it in one to two weeks, considering flow cytometry, again, asking your local hematologist if they have recommendations about doing that, yes or no. I probably wouldn't without consulting. And then unless it's accounted for, you know why the lymphocytes are high. If it's greater than 5,000 for about a month or more, this is according to up-to-date what that recommends. Or there's an abnormal morphology, like the cells look abnormal, then you should probably investigate that one.

If you want a copy of this presentation to kind of keep these numbers, you can sign up with your email below and I'll give you access to that. Sorry this is so wordy and dense, but I just want you to have those reference ranges for you to kind of look at when you're on your own in the clinic. Neutrophils and bands are that next kind of group, and so those are, again, there's a calculation, just pull it up, the absolute neutrophil count calculator. When ANC upgraded to 77, it's considered more like neutrophilia, which has a different kind of pathway of workup. And then the number one thing is the clinical assessment for this one, because again, this one is correlating with a bacterial infection. However, if you have a mildly elevated white blood cell and it's just not that high, and it's all neutrophils, you can consider that repeat workup outpatient with a differential and a smear, which I'll get to when I get to the algorithm.

Eosinophils greater than 1500, that is not expected, because eosinophils again, are allergies and parasitic infection. But if it's higher, in an absolute count is higher, hematologists get a little bit more concerned because they think that it's going to be a bone marrow malfunction. And again, monocytes and basophils are very, very small components of your total white blood cells. And so if those are isolated, elevated basophilia monocytosis, that's much more concerning. And in terms of a bone marrow dysfunction, and so there's no absolute upper limit for those.

The recommendation generally is to refer, and this is from multiple hematologists that I've talked to. And you want to look at the peripheral smear, because most of the time, their peripheral smear is going to look weird, too. Peripheral smear, so again, peripheral smear is looking at the cells underneath a microscope by a pathologist, and it starts with an automated differential that is verified either by a tech or a pathologist, depending on how your lab works, so that's something to think about.

When you get those results, you might see something that says anis... I'm not going to say this right. I'm really not good at pronouncing things, especially new medical terminology. And I've seen it written, but I haven't heard a lot of people say it before. But it is just talking about the size variant. And it's not a red flag, it's just kind of saying that the cells are different sizes, which can happen for a variety of reasons. Poikilocytosis, you'll see that on an abnormal smear. It means it's a variation in the shape. It can be a red flag, there's nothing inherently wrong with it, but it points to a problem, so it warrants evaluation. Blasts absolutely are never normal. Lymphoblasts, myeloblasts, those are oncologic. Those are associated with acute leukemia, so send those puppies right on out.

Basophilia, that's an unexpected, again, because it's considered to be a bone marrow dysfunction, and you will probably see an abnormal smear with these as well, but just send those right out. Smudge cells is consistent with CLL, I believe. I'm not really super familiar with the CML versus CLL situation, but those are things to be seeing a hematologist for. But it's not necessarily urgent unless they're symptomatic, because that's the kind of condition that won't necessarily affect you for 20 years. Schistocytes point to cell destruction, meaning they're kind of torn looking. So inherently, again, nothing wrong with those, but it points that there's a problem with that. And so definitely, those need to go to [inaudible 00:16:40] Metamyelocytes and myelocytes, those are not normal. That points to bone marrow dysfunction because those are early, the progenitors, I think is the word for it.

But the early forms of the white blood cells. And so your white blood cells should be mature when they go into action to fight infection. So if they're getting pumped out really quickly, usually means your bone marrow is not working. And if somebody has symptoms that are consistent with CML, if they have any acute symptoms, they need to go to hematology as well. Just kind of a side note for that smudge cell thing, it goes back to symptoms, again. Other causes of high white blood cells, steroids, lithium, those can also cause a white blood cell count that's slightly elevated. Platelet clumping can cause spurious neutrophilia, again, looking at the specific type of white blood cell neutrophils. It also can cause thrombocytopenia with low platelets, so that's something you want to repeat using a different kind of tube, phlebotomy tube. Smokers can hive have high neutrophils.

If it's a white count of 13 to 15 and they have predominant neutrophilia, could be consistent with a smoker. There's also an idiopathic reason for that, but I'm not really talking about neutrophilia right now, so I'll get into that at another case presentation. Anyway, there's another lab that you can do to kind of see if it's an idiopathic, it's fine kind of thing. And then people with splenectomies can have higher white blood cell counts. What are some steps? Safety again, number one, do they have symptoms? Is it greater than 15 to 20? And do they have anything super weird red flag looking on their peripheral smear? Looking at the types, is this neutrophils, lymphocytes, et cetera? And then, is this reactive or is it a bone marrow disfunction? Or is it other, like those other reasons that I just said, in terms of the medications? Or are they a smoker, or is it idiopathic, something like that? But those are very on the low side, the idiopathic ones.

So what's next? Let's go back to Luis. For him, this is super concerning. We get a call from the lab, the pathologists review the peripheral smear, and it was showing atypical lymphocytes with abnormal morphology. And I think it said favor lymphoma. Sorry, don't quote me on that, I can't remember. I should have written that down. The absolute lymphocyte count that ALC, remember that calculation I told you? You just look it up on MDCalc. It's 49,000, so if you remember, actually, that slide, if you're looking at absolute lymphocyte count, anything greater than 30,000 is going to be concerning, warrantying a hemOnc eval, but in terms of the people who need urgent care, he doesn't have any symptoms. Which, again, I'm getting ahead of myself. So on the lab, they recommended flow cytometry. On the result from the pathologist said, abnormal lymphocytes, abnormal morphology, please order flow cytometry, basically.

So the provider who was on, did, and then did a referral to HemOnc urgently. Again, didn't need to go to the ER because they were asymptomatic, there were no blasts, and he just had his hernia. Sorry, this came out a little bit funky this time, but the CBC, this is where we're going to start with the CBC with high white blood cells. And you're going to look at it if it's greater than 100, again, symptomatic, some to the ER. Or evaluate them if you feel like it's a benign type of, are they coming up with a pneumonia that you're treating actively right now? You don't necessarily have to send those people to the ER, but treat based on the clinical scenario. But if it's over 100, definitely send them to ER.

If it's greater than 11,000, you're definitely going to want to look at the differential, adding it on. You can just call the lab and say, "I'm going to add the differential on if it's been within 24 hours, I think." Peripheral smear, again, is just the verification by the pathologist of the automated differential, typically in most laboratories. You're going to look at the other CBC components, is there anemia, thrombocytopenia, other reasons that you would look to the bone marrow being dysfunctional? And then what are their symptoms, do they have any symptoms? If it's greater than 11 and less than 15, they don't have any symptoms, just recheck it in a week, that's totally fine. Looking at their risk factors and all that, and you can always give people an alarm signs and symptoms, like, "Hey, if you feel fevers, chills, et cetera, et cetera, go to the ER, come back."

But those are people it's less than 15,000. So people, if greater than 15,000 to 20,000 and they have symptoms, you're going to want to do that clinical evaluation and treatment, kind of going back to that first step, like I said. Do they have pneumonia, do they have a UTI? Do they have any other type of infection? Can you safely treat it outpatient, or do they need to go to the ER? That's your clinical judgment, right there. And again, I go by 15, the hematologist that I was talking about was like, "Ah, 20, it's probably okay." 15 or 20, he wasn't really committal with that. And that kind of varies by person to person, I think. And again, if it's greater than 15 to 20 and they have no symptoms, recheck that, but consider flow cytometry, especially if it's predominantly lymphocytes that are elevated.

If it was not lymphocytes, I would not order flow cytometry. You could always just, again, I would call my hematologist if I didn't have an internal medicine that I worked with, internal medicine doc. Or if I had to make kind of a quick decision for some reason, versus a hematology referral. And I could always call them, no problem. Let's go back to Luis. We sent him to HemOnc. It was an urgent referral, but it wasn't emergent. He didn't go to the ER because he didn't have the symptoms, didn't have any blasts on his peripheral smear. He was sent to general surgery for his hernia. And I don't know if I made notes about this written on here, but his blood pressure, if you remember back to the earlier slide, was 130/86, and there are new guidelines.

I'm not really going to touch them in this video, but there are new guidelines that say the goal is less than 130/80, versus less than 140/90. And so that's not consensus right now, there are different things to say about that. For all intents and purposes, his blood pressure was normal. And then the only other thing I wanted to mention was about hernias, is that you want to think about reduceable versus not reduceable. Reduceable, meaning that if it's protruding, you can push it back in and it feels okay, and it kind of stays put or it goes back relatively easily. Versus, if it's painful and it's not reducible, meaning it's sticking out, those people are going to need much more urgent referral and intervention.

Oh yeah, and then just follow up routine care once the hemophilia is completed, because they are kind of taking over that evaluation. And spoiler alert, I'm not doing the full evaluation, but this guy had chronic lymphocytic leukemia, which he underwent treatment for, which is way outside the scope of this presentation, but he did have leukemia.

That's it, I'd love to hear from you. What is one takeaway that you've gotten from this presentation? Something you can write down in the comments to help reinforce your learning and to share with the other NPS and NP students that come to this website about white blood cell count, anything you learned today. I certainly learned a lot doing the research for this presentation and collaborating with that physician. Did you like this video? If so, hit like and subscribe and share with your NP friends so together we can reach as many new grads as possible to make their first year a little bit easier. First couple of years, I should say.

And don't forget to sign up for the email list over at realworldnp.com. You'll get the ultimate resource guide for the new NP if you haven't gotten a copy already. You'll get these videos straight to your inbox every week with little notes from me, and bonus content that I just don't share anywhere else. Thank you so much again for watching. Hang in there and I'll see you soon.