Hematologist Neil Dunavin, MD, a specialist in blood cancers and BMT, elucidates the commonly ordered yet imperfectly understood complete blood count, with guidance on which differential type to order and which results call for investigation. He discusses abnormalities – with causes ranging from sleep apnea to viral infections to rare cancers – and when to consider referral.
you know, the topic of the day is the abnormal cbc. And to be concerned, and, you know, this is my office at UCSF Parnassus. Um and we are on the 12th floor Moffitt. Uh so nice to be with you today. So, what we're going to talk about today is, you know, what, just a little bit of kind of housekeeping info about the difference between malignant hematology and not only the human biology. Um and then we'll talk about the complete blood count and a lot of detail and then we'll go over kind of a number of of worrisome scenarios that you might might see on a cbc uh in line with the theme of the talk, which is kind of went went to be worried. And then we will go over a few slides about how they're kind of expedite or referral to UCSF. And uh and then we'll have some time for, you know, questions over the cat after that. So that is the agenda for today. So, you know, there are kind of subspecialties within specialties and um you know, really, I'm a malignant hematologist. So, you know, my perspective is, you know, I see a lot of patients with blood cancers and malignant hematologist, see leukemia, lymphoma, uh myeloma, mds, they're often the ones seeing a plastic in India doing bone marrow transplants and then diseases like milo milo fibrosis, the milo proliferate diseases. And then when they're seeing kind of patients who don't have a diagnosis, it's usually those where there is some concern for malignancy. Um and then there are non malignant pharmacologists who are seeing the signal cell disease, hereditary hemoglobin diseases like data, bala sena hiring, efficiency, autoimmune diseases, nutritional deficiencies, uh blood clots, anti coagulation, uh coagulation, hemophilia. And then there's kind of gestational hematology or disorders during pregnancy. And and then both of these groups can be involved in the work up of an abnormal cBc. And and we have a kind of a there's you know, about 20 hematology providers in our department and we have a kind of triage system for whatever the uh presenting complaint is. Uh and so uh and there are some idiosyncrasies of the system, whereas uh we're in like, you know, diagnoses like policy, the mandera and essential pharma psychosis. They're technically a cancer diagnosis, but there are often followed by uh I'm not malignant hematologist, so there's kind of two specialties within the specialty. And so, you know, I think it's just helpful to have that distinction. Uh you know, clear and no my perspective is kind of a malignant hematology. That's uh so let's talk for a second about the complete blood count. You know, This is a way to measure the contents of the blood. And you know, there are three cell types in the blood. There are white blood cells. There are red blood cells and there are platelets and the rest of the contents is plasma. And that makes up all your blood. Your blood makes about 500. Uh this should be billion actually 500 billion cells. New cells a day. And your hospital probably does thousands of CDCs today, 20 thousands of species a day in 20% of which will have an abnormal flag of some kind of. Uh so this is probably most of us. This is probably the most common test we're going to look at for every patient. Uh And it's uh so it's it's quite a common thing to go over and see. Um You generally get white blood cell count and a white blood cell differential. And they call it the five part differential because there are five different cell types and the white blood cells. There's the neutrophils, the lymphocytes, the monte cites the basic skills and the S. N. F. L's. And there could be other cells on the smear and those are typically abnormal cells. If if they're there then there are the red blood cell indices. So you get the hemoglobin, the hematocrit and the account the Rbc count and you have the which is the uh you know the level of hemoglobin in the red blood cells. You have the M. C. V. Which is the size the diameter of the red blood cells. And then you have the R. D. W. The red cell distribution with which is how different are the cells from cell to cell. Are there a lot of big and a lot of small or are they all pretty uniform and that you know these to the concentration of hemoglobin and you know or the cannon the cellular hemoglobin concentration. Um We're just gonna forget about those. They're not very important and they're not really used in decision making very much. You get platelets um And um you use some some uh mostly commoners give you a average size of platelets and then a distribution of sizes kind of platelets. Um There are some add on tests that you can order to. A cbc. A ridiculous account is a way you can count the cells that are immature and the red blood cell lineage. So I I think of these like baby red blood cells and you know, your body wants to make a lot of baby red blood cells when you're you know deficient that hemoglobin to catch up. Um Or your body might not be making enough baby friend present bookstores leading to anemia. Similarly, you can also order an amateur platelet fraction. So you can know how many of your how how hard is your body trying to make immature platelet cells? Huh. And so the reference ranges for a complete blood count. You know, are representing the range of results found in 95% of apparently healthy people. So that's how they make the range on the test and what is normal and what is. Uh and I'm not going to show too many pictures. But basically, you know, this is where it all starts. It's the bone marrow and it starts with these large immature cells which we call uh you know uh white blood cell precursors or blast. And um these cells as they mature uh they turn into more mature intermediate forms. And then when they get up to the blood, they make up your nutri fill your S NFL you're basically all your money aside red cells and lymphocytes. So it all kind of starts in the bone marrow and that's where all the cells come from. So there is a two types of complete blood counts that you can generally order from the lab and that is the cbc with emanuel differential and a cbc with the automatic differential. And I think that it's really nice to know the difference between these two. When you order an annual differential, you know, the smear is actually going to be looked at by human which is good. And uh you can also order this test by just ordering a peripheral blood smear uh And this is going to be great for identifying all different kinds of abnormalities in different um you know, blood populations like how do they look? You know, what are their morphological changes? Um And then um You know, you can monitor for a variety of clinical conditions and and it takes about 10 minutes to for the pathologist to go through it. So a lot of hospitals actually put some limits on how many manual differentials they can do. Or they try to use like decision tools to kind of say, you know, um do you really need emmanuel differential in this case? Um For the automatic differential? You know, the equipment used for blood counting is really advanced and they do a very, very good job of differentiating different cell types. So it's a good screen and it's readily reimbursed by insurance results are very rapid. You know, We'll send it out and get results 30 minutes later. And all of these automatic differentials have some defined cut off to where something will get flag and then a pathologist will look at it. So there is kind of a fail safe uh in there. But whenever I see a patient I want to see the manual differential. And sometimes, you know, I want to I want to look at the blood spare myself too. So you know, this is a normal cbc and uh you know this is you know, white blood cell count. And and all of the information we just talked about. And then, you know, usually reference ranges listed like an R. M. R. And you can see where they kind of fall within the reference range. And then uh For the differential, the five part differential, they usually, you know, list of percentage show 48.3 of the total level account uh is uh neutrophils. But they also give the absolute count, which is, you know, the same number as that. So as a hematologist, I'm usually not worried about the percentages as much as I am, the absolute count because, you know, that just gives me a little more information. Um and then, you know, just so you know, like, you know, this is data from the Mayo clinic and you know, in the parentheses, that's the reference range that, you know, they have in their computer. But if you look at a large population based databases like campaigns, um you know, the actual reference ranges are different based on your race and they're not exactly the same as what is in your computer. So when you've got someone who has isolated issues, just a little bit outside the range, it's worth thinking, you know, uh you know, is this something that could potentially be normal for this patient? So that kind of concludes just the introductory, you know, part of just talking about the CBc and then, you know, I'll just go through a few kind of, you know, interesting cases and scenarios now. So, you know, just thinking about what potentially could be, you know, worrisome findings on on a smear, on a blood count. You know, there's really a lot of different things you can see on a blood smear that can give you odds and on a cbc, and uh it's also kind of depending on what the clinical context is too. But um I I will say that, you know, when someone has blasts which are those immature precursors ourselves from the bone marrow out into the blood, you know, that usually is indicative of some kind of a bone marrow disease going on. And so that is something that in general should be be seen by a hematologist. Um and I'll talk about that a little bit more and then there's the immature white cells which are some of those intermediate cells in the bone marrow. Those can get out into the blood and usually those are abnormal to um there are bands which are a type of immature neutrophils and you know at high levels those can you know be a sign of acute infection going on. So that's something to pay attention to. Then you can kind of have like a typical proliferations of lymphocytes and monos sites that can be a sign of an underlying cancer diagnosis When the neutrophils get really low, less than 100. You know less than 500. Um You know people are at risk and all of our patients who are neutral Penick and many of our patients are neutropenia because they're on chemotherapy but you know they have strict instructions to um you know uh you know come to our emergency department or urgent care if they develop a fever because immediately fever you know is one of our medical emergencies. But you know a severe neutropenia that low is is usually an underlying bone marrow problem or a drug effect that needs to be addressed right away. And the marathon beside a pina as well. Similarly as well, you know, the risk of bleeding in that scenario, You know less than 50 is where you you might start seeing some some sign of singer pleading that the less than 10 is something that needs to be addressed. You know one of the human logic emergencies is um you know um is called you know T. M. A. Or robotic micro change apathy. And uh You know you see 50 sites on this year and people usually have a constellation of a media systems, psychosis, fevers, altered mental status and renal failure. And that whole syndrome can be something that needs to be treated right away. So that's usually something encountered in an emergency departments though. And how do immune destruction of red blood cells causing parasites is another problem. Very severe anemia. You know, people have been bleeding chronically or they have a bone marrow disorder. You know, that that is something that used to be uh addressed um in certain situations, you know, you know, endemic for malaria. And that's something you can tell right away just by looking at the blood smear, there's there's malaria atmosphere and those patients, you know, extreme psychosis, very high levels of any of the white blood cell counselors are all things that are going to be worrisome. So let's just do a case really quick. So this is a 32 year old prison with large bruises and fatigue and a cbc is drawn and you know what kind of 7.8, Even though over 7.3 platelets, 44 some of those blood counts are low. Um So you know what next? Um Well we need to know the differential of the white blood cell count because you know, we want to see if there's any sign of a problem in the bone marrow. So you know, we look at the differential and we see that you know there are neutrophils, lymphocytes, monOS sites. But we also see some of these abnormal cells here, the blast cells. And you know if we were to go on much longer, you know, here is another blood count from another Patient. We've got a white blood cell count of 64.1 platelets of 12. But we look out at the differential and we can see that, Oh, there's a lot a really large number of glass. And so this this is a cute leukemia. So that is, you know, something that, you know, people are going to be directed to the emergency department. So what do we do when we hear about something like this? I thought you guys might just be interested in and you know, what happens next, What would be the next step. But in general, when we see those patients who has blasted on the sphere, uh, you know, we are, you know, basically um uh you know, either getting a phone call or we're hearing from an emergency department and then we're either arranging for a mission and to the hospital at UCSF or singing clinic the same day or the next day to arrange an admission from there. And so and then when we do that, we have kind of a list of things we consider, we consider, you know, we check a lot of different tests and we look at the peripheral blood smear ourselves and we check all these different labs for signs of analysis which are the cells kind of breaking up. And we also checked for D. I. C. Which is problems with coagulation. And you know, the reason we look at the smear is because there's a sub types of leukemia that caused problems with Fabulous Nation called a Pl and you want to get them started on treatment pretty quickly because they can run into believing complications pretty quickly, like throw. Um So that's one of the reasons we're looking at the senior very early on and so, you know, because we're a tertiary care center academic center, we have clinical trials, we also have different tests that are ordering to kind of get people even started down the pathway of what different clinical trials they might be eligible for. Because a lot of clinical trials are based on, you know, their molecular, some type of leukemia. So we want to try to get the diagnosis started as quickly as we can because some of these tests have a little bit longer turnaround time. So that's typically what happens. Um, you know, these are the blast and I showed a picture of them earlier. But you know, we look at them and we can see uh these our rods and we have a diagnosis of AML um Uh huh. So here's another case. So a case of side of Kenya's, we've got a white blood cell count of 2.7, a hemoglobin of 10 and platelets of 51. I'll tell you what, I'm already a little bit concerned about this one. You know, everything is a little bit low. And um you know when when general I'm seeing two of the lines are low. I'm suspecting that there is uh potentially an underlying bone marrow problem. And then I look at the M. C. V. And I can see that the M. C. V. Is is really large. That means the average size of the cells is large. So that makes me think well there could probably be a myelodysplastic syndrome here. Um So when you see that macro citic anemia are those really large size red cells? You know you can look at the medications and make sure they're not taking a medicine that's making the red blood cells larger. And you can rule out b. 12 and folate deficiency. Which is pretty rare. You know if people are eating kind of a regular very diet uh and then if you find out that they're normal and you've got a very high fCB, then you're suspecting that there's probably a bone marrow malignancy going on. You know, that patient is being referred, you know, uh you know, urgently to a hematologist, so they can kind of get work underway for the bone marrow back and stuff like that. So you can always consider alcohol consumption with microscopic and immune to. So here is a case of policy India and so this is an elevated hematocrit and this is a really common thing uh to see and referrals and to see in your office. And I'll show you kind of the difference between these two. So this this patient comes in with an elevated hematocrit, 54.3. But, you know, everything else is kind of normal. You know, it's got a normal differential. Um and uh normal neutrophils, normal lymphocytes. Um but here's a case where you've got a little bit of an elevated white blood cell count automatic created 58.4 and a little bit of elevated platelets. And you also see some increases in other parts of the differential. Um So there's um, you know, uh secondary Aretha acidosis and primary Aretha acidosis and secondary your body tells your blood to make red blood cells if it's feeling deprived of oxygen, or if it's getting some hormonal signal to to uh grow more red blood cells. So this would be an example of someone who either has, like sleep apnea and or is on a testosterone supplement or, you know, has uh something uh some chronic oxygen deprivation state where their bone marrow is trying to compensate for it. But the reason then there's also this this diagnosis called policy titanium barrel, which is actually a cancer diagnosis. There's a mutation in your blood that causes your blood to grow more. And um you know, I can pretty much tell this is this is probably septicemia there and this is not just by looking at the blood sparer or at least I've got a strong suspicion because I see the other abnormalities and black sphere as well. So that's just an example in the case of Holy site media. Um and then you can, you know, check the serum erythropoietin, which is the hormone that your body makes to grow red blood cells. If you've got a lot of red blood cells, you know, uh if you're making a lot of red blood cells in your body is not getting the signal to do it. You know, like you might with a cancer mutation, you know, that sarah Marie throw weight and should be really low and you know, that would be a patient that could be referred to a dermatologist to. Uh see is this really this this blood disorder going on? You know if you've got a high serum epo and none of those other abnormalities on the smear. You know, that's a lot of questions about, you know, um testosterone supplementation, supplementation is very common, very common reason. Sleep at night, we'll talk a little bit about isolated neutropenia. This is kind of the next case. Um So just looking at this case, this is a normal white blood cell count 3.4 hemoglobin, a 14.2 Play the account of 1 75. And we just see the nutritional that's just a little bit outside the normal range of uh here's where you might say, Okay, I want to order that manual differential so that, you know, there's a pathologist looking at it under the microscope. And you know, that's what we've ordered. And they say, okay, platelet morphology, unremarkable rbc morphology, remarkable white blood cell morphology possible. So, you know, that everything looks pretty normal under the microscope. So this is something you run into from time to time. And, you know, different ethnicities. And populations of people around the world have a little bit different um, thresholds and cut offs for absolute neutrophils count. And there was a large data study where they looked at, you know, what is the prevalence of neutropenia and primary care settings and what is the significance of neutropenia? And, you know, there was a lot of transient neutropenia. And so pediatric patients, it was 4.9 at 1.9 respectively, over the course of the study. And uh, the Chronis city was much less. It was 0.06% 0.1%. And so common diagnosis and these patients, uh you know, viral infections are very common. And then only a small percentage ended up having a real problem, which is a human to logic malignancy. Similarly with the adults, you know, you know, uh when you were diagnosed with viral syndromes or human to logic malignancy, but most were not diagnosed with anything. So, So you're neutropenia less than 500. You know, that is a big deal. And that's something that will be investigated. And you could be uh, you know, a sign of a severe bone marrow disorder. And 90 of those patients had by side of females. And two of the cell lines are down our pants side of pdf, three of the cell lines without. So, what I take away from this is that, you know, we've got an isolated abnormality. It's always okay to kind of watch it over time. And my usual setup as I you know, check serial cbc as I say, okay we're gonna do this once a month for three months and see is it exactly the same all the time or is it is it um is it changing in some way? And but if you've got two cell lines are down, you know, I'm generally that's my threshold for thinking about doing a rely on scene. So because I'm unwilling to climatologists and I I think a lot about fiction risk. Um and some of you might wonder on your patients who are neutropenia, when when do we use antibiotics to keep infections away? And you know, for in general if it's neutrophils that a little nutritional count that I'm watching with an otherwise related problems, I don't use any antibiotic prophylaxis. But when I do have people on therapy, I uh you know, I use a cycle of era to prevent shingles outbreaks when when people are chemotherapy and then For the duration of their nutritional count being less than 1000, I have people on the the plant. Um and then for the for the for patients who are going to be less than 500 for two weeks, I also use for economies all to prevent basis on the infection. So, you know, that's probably particular to my my patient population, but which are these blood cancers where we're trying to be very vigilant about infection prophylaxis. Um It might be different for other other really intelligent actors. Uh so, you know, wanting to talk about thrown beside a pina for a second. Um so um you know, generally people are various symptomatic with on the side of people that you might not see any signs of Leaving or bruising until the platelet count is less than 30. You know, for us our transfusion goal to keep things, you know safe as an outpatient is greater than 10. And uh And then patients with a plate of the ground greater than 50 were not generally requiring to have any activity restrictions and tolerate most procedures, no surgical procedures. And then if you're seeing a new low platelet count, there's this phenomenon to be aware of called platelet clumping. Um And so some people, their immune system forms antibodies to E to and Geeta is began equipment used and the tube for cbc. S most commonly. And so you can have a little platelet level show up on the analyzer because of that. But it's just because the platelets are clumped up and so you can check platelets and a tube with citrate as the anti violent and that will take care of that and show that there really isn't an issue there. Um, so, you know, a new diagnosis from the side of kenya, you know, um in general, you're, you're trying to rule out whether it's curious or not and then you're looking at the blood smear to see are the platelets really reduced? And what else do I see? Um and so worrisome thing, you can see what's on the side of taenia would be uh signs of Hamal Asus, which is an elevated LDH and decreased captive loving. And analysis is just kind of breaking up of the blood cells and just decides which are kind of like pieces of broken blood cells. And so this is where we would find, you know, a diagnosis like uh, T. T. T, which is traumatic migraines apathy, uh robotic from the side of the program uh and that's a muted reaction to a component of the blood cox called complement. That make sure blood cells breakup and has to be treated with plasma police. So and you know that is uh one of those things that climatologists are always thinking about and then you know if there's no sign of analysis, you know uh common reason that we looked at for these platelets being low um is you know uh issue with a drug that's been taken uh which there are lists of maybe hundreds of drugs that can cause isolated homicide of. Uh And if you can't find any underlying cause, you're looking at kind of immune causes like I. T. P. And if there are two cell lines, you know, you're generally looking in the bone marrow to make sure that there is no evidence of a life cancer too. So when you have low platelet counts you can always turn to the smear and say, you know what do I see? And you know if you ordered a manual differential you might get some of this extra information on the cBc report. You know if you see a typical emphasis uh for large granular lymphocytes sometimes they call them. You can think about viral infections and I'll just pull out a few of these for examples. But if you see nuclear red blood cells red blood cells that still have a nucleus in the middle, you know you're thinking about analysis and bone marrow disorders. Um if you're seeing macro psychosis you can think about you know B. 12 full eight and uh MBS of oh no disorder. And then you know she's besides what we're thinking about T. V. D. And then just say to put a face to the name. You know what is that pathologist looking at under the microscope with the red cells. You know they're kind of saying as a normal sized small large ovoid how much hemoglobin concentration do it has Which is the Crimea you know what's it shaped like there's a single cell, there's a sister site. Um And what kind of inclusions are kind of in the cell. So you know my experience from just seeing patients with consults that there's a lot of um you know things that you can watch and uh you know if you see a transient isolated asymptomatic increase in neutrophils or decrease in major fails increase in platelets or decrease in platelets or increase income, adequate transient increase in E. S. N. F. L. Is a common line. There's a very very large work up you can send for ESPN ophelia but uh kind of good to confirm that it's not something that goes away within the next blood check. So my my general way to handle an asymptomatic patient with one of these findings that can translate. It would be to check serial uh serial labs over a series of time points. Uh And I would order that manual differential on the Cbc too so that you know everything is being looked at carefully by by an operator. You can kind of see multiple time points and trajectory to touch anything that might be continued. Yeah. So you know that was just kind of a general introduction to the cbc and just a few interesting cases just kind of thinking about what we might see on consults and kind of to close out. I'm just going to talk a little bit about referral process for UCSF and then we'll you know have some time for some questions, but you know, we're always available and wanting to help and you know, we're always um you know, interested in looking at cbc results, that's kind of what we do every every day. We're also kind of used to working in a situation where you know, things need to be taken care of quickly and this is an acute issue. So, you know, I would say as a group we try to get, especially on the million hematology side, we try to get people in very, very quickly so that we can get things rolling. You know, if we're thinking about good reasons to kind of phone in that urgent console, you know, last on the personal smear, severely low platelets are neutrophils to blood size are down or where there's an elevated psychosis of some kind, you know, it's not blast. Um Uh huh. So uh you know those are and then just a sites those are all good reasons to consult the metallics originally. Um My biases that blast or a good reason to be seen in a tertiary referral center because you know when you're going through a diagnostic work up for leukemia, you know, it's a lot of specialized testing and then the consideration for clinical trials is also important for for the karat humans, logical tendencies. Uh And then you know ethnicity of the problem can be helpful the triage. So you know, how long has it been there? So you know getting old records is there's a lot of time I spend a lot of time trying to get all records and all blood counts two. What can see what was what was there before.
