[SPEAKER_00]: Welcome back to Run the List.
[SPEAKER_00]: My name is Emily Gatowski, and I'm here with Dr. Noah Ripple, graduating Chief Fellow from Mount Sinai, He-Mong Fellowship, an incoming assistant professor at the Mount Sinai Tisch Cancer Institute.
[SPEAKER_00]: And today we're gonna be talking about the topic of Luko Saitosis.
[SPEAKER_00]: Noah, thank you so much for joining us.
[SPEAKER_01]: Thank you so much for having me, Dr. Gatowski.
[SPEAKER_01]: I'm really excited to be here.
[SPEAKER_01]: I'm looking forward to talking all of things Luko Saitosis.
[SPEAKER_00]: Lucocetosis is something that comes up all the time and there is a pretty big differential which we're gonna go through.
[SPEAKER_00]: So let's get into it.
[SPEAKER_00]: Today we have a 71 year old female with a history of hypertension, hyperlipidemia, COPD.
[SPEAKER_00]: And she's admitted overnight to the general medicine floor with generalized weakness and shortness of breath.
[SPEAKER_00]: Her vitalsign show Mile Tech a cardiac 103.
[SPEAKER_00]: She's a Fabrile, her blood pressure is normal and her O2 set is 96% on remare.
[SPEAKER_00]: Her laps are coming back and show a white blood cell count of 28,000.
[SPEAKER_00]: A hemoglobin of 11.8, platelet count of 310, and the overnight team empirically starts broad spectrum antibiotics, looking at that white count, presuming an infection, while the rest of the work up is ongoing.
[SPEAKER_00]: So Dr. Ripple, what do you think about this case so far?
[SPEAKER_00]: Is the team right to jump straight to an infection, or what are some other potential causes of glucose atosis?
[SPEAKER_01]: This is really great case and one that we see so often.
[SPEAKER_01]: So we know that a normal white blood cell count can range from 4,000 to 11,000 cells per microliter and this is usually composed of about 40 to 60 percent neutrophils, 20 to 40 percent lymphocytes and then monocytes tend to be less than 8 percent.
[SPEAKER_01]: eucinophils less than 5%, and basophils are quite rare, usually less than 1%.
[SPEAKER_01]: So, the species clearly has a leukocytosis, and it's also important to note her other labs.
[SPEAKER_01]: We know she has a mildenemia, and we see that her platelets are preserved.
[SPEAKER_01]: You know, before we jump to infection, which is always tempting, I try to take a step back and think about the patient as a whole.
[SPEAKER_01]: Good history and good exam findings can really go a long way in hematology.
[SPEAKER_01]: and we never want to get fooled by what can sometimes be a red herring.
[SPEAKER_01]: So, what's on my differential?
[SPEAKER_01]: I would say first and foremost is COPD.
[SPEAKER_01]: It's important that we ask care what she's taking for that.
[SPEAKER_01]: Some patients keep emergency oral steroids on hand at home for COPD exacerbations.
[SPEAKER_01]: Could she have taken some prednisone earlier this week when she started feeling short of breath?
[SPEAKER_01]: Alucosatosis of 20,000 driven by just a short course of oral steroids would be a bit unusual and a bit of a hard cell, but is it impossible?
[SPEAKER_01]: especially if there's a concurrent infection that's driving the COPD exacerbation in the first place.
[SPEAKER_01]: I would say that brings us to number two, infection and that's absolutely on our list.
[SPEAKER_01]: Respiratory infection makes sense given the story, but we do need more context.
[SPEAKER_01]: What is her x-ray look like?
[SPEAKER_01]: Do we have any blood cultures?
[SPEAKER_01]: Year analysis, it is totally fair that the overnight teams started antibiotics, but we should not stop our thinking there.
[SPEAKER_01]: We should also think about other causes.
[SPEAKER_01]: Does she have any risk factors for aspiration?
[SPEAKER_01]: We know that aspiration in unites can also certainly drive the white count up from the inflammation alone.
[SPEAKER_01]: PE or pulmonary embolism is another important thought here.
[SPEAKER_01]: It can cause stress-related lucosatosis and can certainly also drive a COPD exacerbation.
[SPEAKER_01]: Could she be dehydrated?
[SPEAKER_01]: We know the dehydration can cause hemoconcentration, where our plasma volume decreases.
[SPEAKER_01]: making our counts appear relatively higher.
[SPEAKER_01]: But with that being said, in that case, we would expect all her cell lines to be proportionately elevated, which doesn't seem to quite fit here.
[SPEAKER_01]: We can also see Lucco Sato-Sis as a simple physiologic stress response in a cutely OP-sheets, but this would be another tough cell here, given that the white count is all the way up to 28,000.
[SPEAKER_01]: And then, of course, there's the never-miss category.
[SPEAKER_01]: And you keep leukemia as the big and scary one to keep in mind.
[SPEAKER_01]: It is less likely here, given that her hemoglobin in pleatlets are relatively preserved.
[SPEAKER_01]: And as far as we know, she has no blasts on her automated death, but it's always in the back of my mind.
[SPEAKER_01]: There are also chronic bone marrow disorders to think about, things like myeloproloperative neoplasms or MPNs.
[SPEAKER_01]: but we need more data to make that determination.
[SPEAKER_01]: I really want to emphasize here, clinical contacts and the rest of the initial workup matter just as much as the white count itself.
[SPEAKER_01]: What does her CMP or comprehensive metabolic panel look like?
[SPEAKER_01]: What about the full automated differential?
[SPEAKER_01]: does she have bands?
[SPEAKER_01]: Does she have blasts or anything else unexpected there?
[SPEAKER_01]: And the chest X-ray isn't just looking for an ammonia.
[SPEAKER_01]: I'm also looking for masks, if fusion's cardiomegaly, all of these things can really affect how we interpret her white count.
[SPEAKER_01]: Of course, we need a thorough med rec.
[SPEAKER_01]: Steroids are not the only culprit when it comes to thinking about elevated white blood cell currents, even beta agonists, things like albutarol, which she may well be on for her COPD, can cause leukocytosis.
[SPEAKER_01]: So, all to say that every detail matters here.
[SPEAKER_00]: So, just to continue setting the stage for the topic of lukosytosis, can you talk a little bit about the actual mechanism what goes on inside the body when the white count goes up and does it depend on the underlying cause of the lukosytosis?
[SPEAKER_01]: It certainly does depend on the underlying cause and these are definitely important to know, with infection it's pretty sweet forward.
[SPEAKER_01]: and pushes them out into the periphery, into the blood.
[SPEAKER_01]: With malignancies, we know that there is an abnormal clove, and that's proliferating in an abnormal, uncontrolled way.
[SPEAKER_01]: So the cells themselves are the problem.
[SPEAKER_01]: But here's the one that really tends to trip people up.
[SPEAKER_01]: Sometimes the white count goes up without any new cells being made.
[SPEAKER_01]: and we call that de-margination.
[SPEAKER_01]: At any given point, we know that roughly half of our neutrophils are really circulating through the blood, but the other half are actually loosely stuck to the blood vessel walls.
[SPEAKER_01]: That's what we call our margenyneated pool of cells.
[SPEAKER_01]: When something causes those cells to unstick and flood back into the circulating pool of cells, our measured white countries, even though the total number of neutrophils in our body
[SPEAKER_01]: The classic example for this is steroids and that's the one that always gets tested.
[SPEAKER_01]: The main way that steroids do this is by making neutrophils less adhesive so that they detach from the blood vessel walls.
[SPEAKER_01]: We definitely also see demargination with other conditions such as obesity and the way that that works is that cytokines end up getting released from
[SPEAKER_01]: and they cause the same kind of nutritional distribution or de-margination.
[SPEAKER_01]: Stressors is another good cause and that can be physical stressors, emotional stressors, and that can lead to inedrophilic predominant glucosatosis that similarly to steroids is also driven by de-margination, and here it's caused by a catechole means surge.
[SPEAKER_01]: Finally, another cause to not forget is that the spleen actually sequester is a pretty meaningful chunk of our body's cells, not just white cells, and so when a patient is a splinic, we can definitely also see a bump in their white count.
[SPEAKER_00]: super interesting.
[SPEAKER_00]: Thank you for taking us through that.
[SPEAKER_00]: So in this case, it would be helpful to know what her most recent labs prior to this presentation look like, so we can get a sense of the acuity of this leukocytosis or the time course.
[SPEAKER_00]: Unfortunately, she hasn't been to a doctor in about three years, so this is the first piece of information we really have for a long time.
[SPEAKER_00]: If we did learn that her white blood cell count last month was around the same,
[SPEAKER_01]: Yeah, this is such a great point, and so important.
[SPEAKER_01]: I would say that current city is really huge.
[SPEAKER_01]: Acute lucusatosis develops over hours or days, and this is where we think about things like infections, steroids, bodily stressors, acute inflammation, and potentially also abruing acute malignancy.
[SPEAKER_01]: Chronic is more along the course of weeks, two months, and even years, and that's a completely different ball game.
[SPEAKER_01]: And so, if our patients' white count was the same a month ago, I would say that malignancy does move out my list.
[SPEAKER_01]: And PNs become a real consideration, because we can see Lucas say to us as with any of them.
[SPEAKER_01]: things like essential thrombosatemia, polysatemia, vira, pre-fibrodic malafibrosis, and even CML.
[SPEAKER_01]: PV is a bit less likely here, just given the fact that she has a low hemoglobin, but it's not impossible if something else like an nutritional deficiency is pulling the hemoglobin down.
[SPEAKER_01]: I would definitely be looking closely at the various elements of the differential on her CBC to make some of these differentiations.
[SPEAKER_01]: And then on the reactive side, chronic infections, things like osteomyolitis, TB, and abscesses,
[SPEAKER_01]: should at least be entertained if there's anything concerning for these in her clinical context.
[SPEAKER_01]: And then there are also the chronic inflammatory conditions, things like IBD, rheumatoid arthritis, vascularitis.
[SPEAKER_01]: These should be on our differential, although they do seem somewhat less likely in an older patient who is not already known to have any of these diagnoses.
[SPEAKER_01]: And then of course, chronic steroids.
[SPEAKER_01]: This is an important point.
[SPEAKER_01]: Steroid induced neutrophilia typically presents with mature neutrophils without a left shift.
[SPEAKER_01]: And this can be really helpful in distinguishing it from infections.
[SPEAKER_01]: Smoking is another possible cause of chronic glucosatosis, but usually too much milder degrees, so it's less likely here.
[SPEAKER_01]: And asplenia is also relevant here as well.
[SPEAKER_01]: I would definitely also like to take a look at her blood smear under the microscope, and if the entire preliminary work up is negative, I think I would move pretty quickly to sending a peripheral blood flow cytometry, and also potentially doing a bone marrow biopsy in this case.
[SPEAKER_00]: So that's definitely getting us thinking about getting the hematology team involved when we see a number like this.
[SPEAKER_00]: Let's move on to the differential that comes along with the CBC often referred to as the diff.
[SPEAKER_00]: I remember when I first started rotations I kept hearing phrases like Nutrophilic predominance or left shift and I was very confused.
[SPEAKER_00]: I felt like everyone else knew some sort of lingo that I didn't know.
[SPEAKER_00]: So can you help us understand how the specific types of white blood cells being elevated narrows the differential and what these terms mean?
[SPEAKER_01]: Yes, absolutely.
[SPEAKER_01]: Maybe we can start with a quick refresher.
[SPEAKER_01]: Our white blood cells fall into three big buckets.
[SPEAKER_01]: The first are granulocytes, and that's really the big one.
[SPEAKER_01]: Granulocytes are named for the granules in their cytoplasm, and these include our neutrophils, our beesophils, and eucinophils.
[SPEAKER_01]: Then we have our lymphocytes, which are t-cells, b-cells, and natural killer cells,
[SPEAKER_01]: And then finally we have monocytes and these are the precursors to macrophages and during excels and they're responsible for the body's immediate non-specific kind of first-line device in terms of left-shift.
[SPEAKER_01]: That just means that immature granular sites are showing up in the poor full blood.
[SPEAKER_01]: The fun fact for the storm is that it actually comes from old lab counters, the listed cell maturity from left to right, and so the more immature cells basically meant that there was a shift to the left on the lab counters.
[SPEAKER_01]: Now, when it comes to mirroring our differential by the types of white cells that we see, neutrophils tend to get us thinking about bacterial infections.
[SPEAKER_01]: That's a classic.
[SPEAKER_01]: But if we're seeing immature myloid cells, things like neutrophil bands, mylo sites, metamilocytes,
[SPEAKER_01]: You need to ask yourself if this is a reactive left-shift from a bad infection, or could this be something else like CML?
[SPEAKER_01]: CML or chronic myloid leukemia gives us myloid cells at all stages of maturation, and another important diagnostic clue for CML would be if we see bees of philia.
[SPEAKER_01]: Isolated bees of fillia is a reactive finding is extremely extremely rare.
[SPEAKER_01]: And so if I see bees of fillia on the CBC differential, and especially if it's present with concurrent immature myloid cells, they usually does put CML high up on my differential.
[SPEAKER_01]: Now, when it comes to lymphocytes, those get me thinking about viral infections, but in an older patient with a persistent lymphocytosis, CLL would definitely be high on my read R. Eocinophils get me thinking about pericake infections as my allergies drug reactions like dress syndrome, and there are certainly also clonal blood cell disorders that involve Eocinophils,
[SPEAKER_01]: things like chronic and acute eucinophilic leukemias.
[SPEAKER_01]: Just a couple more important points when it comes to this.
[SPEAKER_01]: The first is that we should never look at the white blood cells in isolation.
[SPEAKER_01]: For example, if we see nucleated red blood cells on our CBC, that's never a normal finding because it indicates the bone marrow is pushing out red blood cells before they've had a chance to mature.
[SPEAKER_01]: And so if we see a leukocytosis with immature myeloid cells with concurrent nucleated reds,
[SPEAKER_01]: We call that condition, luko, a rethroblastosis.
[SPEAKER_01]: And that basically means that we have to at least think about the possibility of a marrow occupying process, such as male fibrosis, with marrow scarring, or a potentially metastatic cancer that's infiltrating the bone.
[SPEAKER_01]: Finally, it's really important to remember that what we see on the automated differential never tends to be the full story.
[SPEAKER_01]: And it can actually mislead us
[SPEAKER_01]: These machines can induce classifying cells.
[SPEAKER_01]: And so when something doesn't add up, just call us, have a look at a blood smear.
[SPEAKER_01]: This is such an underutilized, but an incredible diagnostic tool.
[SPEAKER_00]: Awesome, thank you for that.
[SPEAKER_00]: So moving along in this case, our infectious work up thus far has actually been negative.
[SPEAKER_00]: Her chest x-ray comes back clear, her UA and CMP are normal, and her cultures have all come back negative.
[SPEAKER_00]: So what's next?
[SPEAKER_00]: What other labs can we obtain that might help us here?
[SPEAKER_01]: Yeah, so I think first thing I would do is I would actually circle back to the patient's history.
[SPEAKER_01]: Is there anything that could be suggestive for autoimmune disease?
[SPEAKER_01]: Does she have any GI symptoms that could point potentially to undegged, noist, inflammatory bowel disease?
[SPEAKER_01]: Does she have any constitutional symptoms?
[SPEAKER_01]: Things like fever, night sweats, weight loss, anything that would hint at a potential malignancy.
[SPEAKER_01]: I would also specifically ask about abdominal discomfort early satiety, if she has any itching, any brain fogginess.
[SPEAKER_01]: These are MPNS-associated symptoms that patients don't always necessarily volunteer, unless we explicitly ask about them.
[SPEAKER_01]: In terms of labs, a peripheral blood smear is really a must, and if absolutely nothing comes back positive on our initial workup, I would also say that peripheral blood flow cytometry would be important here as well, and that could potentially be followed by a bone marrow biopsy with cytogenetics and molecular studies as one of our next steps.
[SPEAKER_00]: Okay, excellent.
[SPEAKER_00]: Moving on to day two of our patient hospitalization, the white blood cell count continues to rise.
[SPEAKER_00]: It's climbed from 28,000, the first day to 39,000, the next day, and then by that afternoon 45,000.
[SPEAKER_00]: So we're starting to get a little bit worried.
[SPEAKER_00]: The next day, it's 65,000.
[SPEAKER_00]: We've consulted hematology at this point for assistance, but we're also starting to worry not only about the underlying reason for the leukocytosis, but the actual effect of such profound leukocytosis on the body.
[SPEAKER_00]: Can you talk a little bit about this?
[SPEAKER_01]: Absolutely, this is such a good question.
[SPEAKER_01]: So with the rapidly rising white count like this, malignancy now has to be high on our differential.
[SPEAKER_01]: We do rarely see white counts this high
[SPEAKER_01]: work applies.
[SPEAKER_01]: This is a situation where we definitely would move on the faster side.
[SPEAKER_01]: After we again carefully review the automated differential, I would definitely obtain another peripheral blood smear at this point and manually review it again.
[SPEAKER_01]: Things can change and maybe the species did have a brewing acute leukemia and we may suddenly see the appearance of blasts on the blood smear that may have not been there before.
[SPEAKER_01]: This is also when we need to make sure that we have things like two more lysis markers.
[SPEAKER_01]: Yurik acid, calcium, phosphorus, potassium, and case this really is a new cancer.
[SPEAKER_01]: Also, really important here would be collagulation studies, and if I burn a gen so that we can rule out DAC or disseminate it into a vascular collagulation.
[SPEAKER_01]: If this was present, this would raise my concern for APML, or acute promylesidic leukemia.
[SPEAKER_01]: And I would most likely move ahead at this point with an urgent bone marrow biopsy.
[SPEAKER_01]: Now, in terms of getting to the effect on the body of the elevated white blood cells, this would totally depend on what types of white blood cells are driving this count.
[SPEAKER_01]: Blasts are really the scary ones.
[SPEAKER_01]: And that's because they're large, they're sticky, and they basically sludge up our small blood vessels.
[SPEAKER_01]: That's what we call the prosthesis.
[SPEAKER_01]: When these large sticky cells block blood vessels and hurt our various organs, they result, and some big signs and symptoms to keep in mind are dyspnea, sometimes I poxial with infiltration imaging, and also neurologic symptoms of any kind, and these can range all the way from mild confusion to full-blown strokes.
[SPEAKER_01]: And in AML, or acute mild leukemia, we get concerned for leukostasis when the white blood cell count is higher than about 100,000 cells, which is called hyperlucosatosis.
[SPEAKER_01]: And in some subsets of AML, we could also see lucostasis with as fused 50,000 white blood cells.
[SPEAKER_01]: On the other hand, we have patients with conditions such as CLL, or chronic lymphocytic leukemia, and these patients can sit with white blood cell counts that are often in the many hundreds of thousands, composed of all matral lymphocytes, and these patients feel completely fine.
[SPEAKER_01]: They may not even meet criteria for treatment, which is crazy, right?
[SPEAKER_01]: We get called for these patients all the time because their numbers looked terrifying, and our answer is usually, don't worry about it.
[SPEAKER_01]: There are small material lymphocytes, and they don't tend to cause the prosthesis.
[SPEAKER_01]: Now, in terms of how we treat the qustesis, we tend to, marginally, go ahead with cytoreduction to get rid of the blasts in our blood.
[SPEAKER_01]: Hydroxyuria tends to be a drug of choice in the acute setting, and that's because it's non-specific.
[SPEAKER_01]: It works within hours, and it's oral.
[SPEAKER_01]: So until we have our diagnosis, it's effective, and then afterwards, we can initiate chemotherapy.
[SPEAKER_01]: In terms of other things like glucoforysis, the data just doesn't show a consistent survival benefit over hydroxyuria alone.
[SPEAKER_01]: It's much more resource intensive, and it requires patients who already tend to be quite sick and prone to infections and to bleeding to have large bore access placed.
[SPEAKER_01]: And so when it comes to Luca for recess, we tend to really reserve this for some traumatic patients whose Luca's status is not responding to any other measures.
[SPEAKER_00]: Thank you for explaining that.
[SPEAKER_00]: I know this is a topic that might not come up as often as just regular lukosytosis, but when we get to these more advanced numbers, these are absolutely factors that we need to consider.
[SPEAKER_00]: So let's take a step back and pivot to a slightly different version of this case.
[SPEAKER_00]: Suppose the same patient had a mildly elevated white blood cell count.
[SPEAKER_00]: for 10 plus years, hovering around 12.5 to 14, let's say.
[SPEAKER_00]: And they've undergone a work-up for concerning underlying causes, but that's really been unrevealing.
[SPEAKER_00]: What could be going on with a mild leukocytosis that's chronic?
[SPEAKER_01]: So now we know that our patient has a mild lucrative psysosis that's been rock-solid stable for over a decade.
[SPEAKER_01]: I'm super reassured by that.
[SPEAKER_01]: No emergent blood disorder stays stable and without associated symptoms that long without treatment.
[SPEAKER_01]: And so right off the bat, we can be pre-sure that this isn't an acute leukemia.
[SPEAKER_01]: And so we shift our thinking toward chronic causes.
[SPEAKER_01]: Could this still be a chronic inflammatory condition or potentially smoldering infection?
[SPEAKER_01]: Sure.
[SPEAKER_01]: But honestly, at the slow level dukeusatosis and for this duration, I'm also thinking about lifestyle and comorbidity driven causes.
[SPEAKER_01]: Things like obesity,
[SPEAKER_01]: obstructive sleep, apnea, or OSA, smoking, and even medications.
[SPEAKER_01]: Of course, chronic malignancies are still possible.
[SPEAKER_01]: Things like MPNs, CML, CLL, can all simmer for years with stable counts.
[SPEAKER_01]: And sometimes this low-level lucosatosis is really just where the patient lives.
[SPEAKER_01]: What I'd really want to look at here is the white cell differential.
[SPEAKER_01]: Are there any subtle open or maladies that are hiding there?
[SPEAKER_01]: And what are the hemoglobin and platelets been doing over the same period?
[SPEAKER_01]: These trends can actually be incredibly revealing.
[SPEAKER_01]: And of course, history and exam are still key.
[SPEAKER_01]: We need to check for lymphed and not but these supplement omega-ly and ask about those constitutional symptoms.
[SPEAKER_01]: If any of those red flags are present, they weren't for their work up, even if our patient has had a stable count for this long.
[SPEAKER_00]: Thank you.
[SPEAKER_00]: That's really helpful.
[SPEAKER_00]: I know I've had many patients who have had these chronic low-level leukocytosis and it's always helpful to have a hematology referral just to make sure we're not missing anything but as you said some people just live in a higher reference range and we have to remember that these reference ranges are established based on most people's normal but that does not include everyone.
[SPEAKER_00]: As we are wrapping up this topic and this has been a wonderful discussion of leukocytosis, do you have any other clinical pearls or take home points
[SPEAKER_01]: Yeah, absolutely, I think an important pearl that we had in touch on yet is that when we value a patient's white blood cell differential in a patient with lucosatosis, we should never be looking at the percentage of white blood cell types.
[SPEAKER_01]: It's really the absolute counts that matter, not their relative percentages.
[SPEAKER_01]: And this comes up all the time and is such an important
[SPEAKER_00]: It's a very good point, and I, in my rheumatology world, we often look at on the other end, Luko Pinia, and sometimes the percentage can be low, but the absolute number can be normal or vice versa, and always good to take into account the absolute, you know, lymphocider and nitrifle account.
[SPEAKER_00]: So, the same goes for the other end of the spectrum as well.
[SPEAKER_00]: And any final take home points before we wrap up here?
[SPEAKER_01]: This has been such a good discussion, and I think a couple of important take home points would
[SPEAKER_01]: Good history, good exam, always.
[SPEAKER_01]: I would also say never look at one CBC in isolation, just like with any other labs, trends really do matter.
[SPEAKER_01]: And also, always try to order a differential with your CBCs.
[SPEAKER_01]: The total white count just isn't informative enough, and we need to know what the breakdown is.
[SPEAKER_01]: The only exception for this might be for a patient undergoing routine pre-op screening in an otherwise healthy patient.
[SPEAKER_01]: But if you're trying to figure something out, you do need the differential.
[SPEAKER_01]: And lastly, I would say, don't get stuck on red herrings.
[SPEAKER_01]: This isn't just for leukocytosis or even just for him.
[SPEAKER_01]: leukocytosis doesn't always mean an infection, and a normal white count doesn't always roll it out either.
[SPEAKER_01]: So I would say think critically, look at the whole picture, and try to not let just one number drive your decision-making.
[SPEAKER_00]: perfect.
[SPEAKER_00]: This has been a wonderful discussion.
[SPEAKER_00]: I think we can all feel much more confident handling patients with elevated white counts due to your expertise.
[SPEAKER_00]: So thank you so much now for joining us.
[SPEAKER_01]: Thank you so much for having me, Emily.
[SPEAKER_01]: It was such a pleasure.