WEBVTT 00:00:00.800 --> 00:00:01.968 Good afternoon everyone. 00:00:01.968 --> 00:00:06.597 Welcome to today's presentation entitled Hematology M+Ms, 00:00:07.056 --> 00:00:10.018 Morphology and Mystery using a case study 00:00:10.018 --> 00:00:13.021 approach presented by Karen Brown. 00:00:13.062 --> 00:00:14.647 I'm Holly Banks, the education 00:00:14.647 --> 00:00:17.900 event coordinator for ARUP's Institute for Learning. 00:00:18.526 --> 00:00:21.529 I'll now turn our time over to Karen. 00:00:21.529 --> 00:00:24.323 We'll begin with an overview of some basic concepts 00:00:24.323 --> 00:00:29.620 that are related to the use of morphology when identifying peripheral blood cells. 00:00:29.912 --> 00:00:34.542 And then we're going to use case studies to focus on these morphologic guidelines. 00:00:34.542 --> 00:00:39.130 And how morphology is still a very important adjunct test 00:00:39.130 --> 00:00:43.676 in helping to define various define various hematologic disorders. 00:00:45.011 --> 00:00:49.390 The cases in this presentation have been derived from a face 00:00:49.390 --> 00:00:53.394 to face presentation that included more numerous case studies. 00:00:53.936 --> 00:00:59.609 The case is selected for review in this presentation have been maintained 00:00:59.609 --> 00:01:02.737 in the numbers that were used in the original presentation. 00:01:02.904 --> 00:01:07.283 These cases represent only a few of the ones that I normally present. 00:01:08.576 --> 00:01:09.494 These are the 00:01:09.494 --> 00:01:12.497 objectives for today's session. 00:01:12.789 --> 00:01:15.792 Before we actually get into, 00:01:16.125 --> 00:01:18.294 the case studies, I'm going to talk a little bit 00:01:18.294 --> 00:01:22.673 about some background information, and I can't emphasize enough, 00:01:23.091 --> 00:01:27.095 as we move forward, the importance of having a well-prepared, 00:01:27.678 --> 00:01:30.556 peripheral blood smear with a good distribution of our red blood 00:01:30.556 --> 00:01:36.062 cells, and also to have an important how important it is to have a good stain. 00:01:36.270 --> 00:01:39.398 So when we look at red blood cells, we have to, 00:01:39.732 --> 00:01:43.069 assess the distribution of these cells and the stain. 00:01:43.277 --> 00:01:48.199 And for those of you that are well seasoned in looking at smears, 00:01:48.199 --> 00:01:52.120 you can recognize sometimes that the stain just isn't where we need it to be 00:01:52.370 --> 00:01:53.538 and can deal with that. 00:01:53.538 --> 00:01:57.500 But I always encourage you, if there are issues, with the stain 00:01:57.500 --> 00:02:03.256 and you can remake a smear and re stain it if, it can be very important to do so. 00:02:03.589 --> 00:02:07.343 And we're going to be talking about some cases moving forward where having 00:02:08.845 --> 00:02:13.141 morphology abnormalities is significant. 00:02:13.141 --> 00:02:15.935 And if we don't have a good stain and we don't have 00:02:15.935 --> 00:02:18.938 good distribution of our cells, and that can be problematic 00:02:19.313 --> 00:02:22.316 when we look at our red blood cells, we are evaluating them 00:02:22.316 --> 00:02:24.026 for basically five different areas. 00:02:24.026 --> 00:02:26.028 We want to look at their overall size. 00:02:26.028 --> 00:02:28.406 We will look at their shape. 00:02:28.406 --> 00:02:31.409 We want to to look at the central pallor, 00:02:31.409 --> 00:02:34.412 or the area of hemoglobin content within the cell. 00:02:34.787 --> 00:02:38.624 And the area of central pallor should be about a third of the diameter of the cell. 00:02:39.292 --> 00:02:43.045 And then, of course, we also look to see that, the red cells, 00:02:43.671 --> 00:02:46.674 do not have any inclusions, which is the normal state. 00:02:46.757 --> 00:02:50.219 And of course, they're always going to be variations in size and shape 00:02:50.720 --> 00:02:51.470 and the cells. 00:02:51.470 --> 00:02:55.224 But it's important to recognize what is significant and what is not. 00:02:56.350 --> 00:03:00.646 So here is a nice image of some, red blood 00:03:00.646 --> 00:03:05.067 cells that are essentially normal in their size and their shape. 00:03:05.443 --> 00:03:08.321 They are evenly distributed throughout the smear. 00:03:08.321 --> 00:03:11.324 And then they also have a good, 00:03:13.159 --> 00:03:13.868 Central pallor. 00:03:13.868 --> 00:03:17.538 You can see here that we have nice central pallor in these cells. 00:03:17.538 --> 00:03:21.709 This particular cell over on the left is a little bit skewed in its shape, 00:03:21.834 --> 00:03:24.420 but that's certainly not anything that's abnormality. 00:03:24.420 --> 00:03:27.381 Up here we see a little bit of an overlap in the cells. 00:03:27.381 --> 00:03:31.219 But there again there is nothing unusual when we see another area 00:03:31.219 --> 00:03:32.929 over here with some overlap. 00:03:32.929 --> 00:03:37.141 So our red cells become very useful in assessing whether we truly do 00:03:37.141 --> 00:03:40.144 have that good area on the smear. 00:03:42.230 --> 00:03:43.022 Now when we talk 00:03:43.022 --> 00:03:46.025 about identifying leukocytes and white blood cell 00:03:46.275 --> 00:03:49.487 morphology, there are certain guidelines that are helpful as well. 00:03:49.779 --> 00:03:54.242 And of course, much as this still applies to maturation and morphology 00:03:54.242 --> 00:03:58.287 of our red blood cells, but in general, as cells 00:03:58.287 --> 00:04:01.916 mature, we're going to see they decrease in their cell size. 00:04:01.916 --> 00:04:05.211 And this, as I mentioned, becomes very important when we're trying to assess 00:04:05.878 --> 00:04:08.506 the morphology of white blood cells, particularly 00:04:08.506 --> 00:04:11.509 when we're looking at potentially immature cells. 00:04:11.509 --> 00:04:16.639 The chromatin becomes more clumped and condensed as the cells mature. 00:04:16.639 --> 00:04:20.184 And of course, in the case of red blood cells and nucleated red blood cells, 00:04:20.184 --> 00:04:24.272 that nucleus is going to be expelled as this as the cell matures. 00:04:25.231 --> 00:04:26.816 In segmented 00:04:26.816 --> 00:04:30.111 neutrophils, of course, we see light develop in our cells. 00:04:30.111 --> 00:04:32.863 And that helps, define those cells. 00:04:32.863 --> 00:04:37.576 The cytoplasm becomes more abundant relatively as the cell matures. 00:04:37.576 --> 00:04:40.913 And in the case of red blood cells, the coloration 00:04:40.913 --> 00:04:44.875 changes from blue to red in, the mature red blood cell. 00:04:44.875 --> 00:04:46.460 And then in the case of granulocytes, 00:04:46.460 --> 00:04:49.463 for instance, we will see granules that develop. 00:04:50.381 --> 00:04:53.843 This schematic is designed to show these nuclear 00:04:53.843 --> 00:04:56.971 and cytoplasmic changes that occur in our red. 00:04:57.722 --> 00:05:01.058 Well this is showing our, white blood cells, but also 00:05:01.600 --> 00:05:02.810 applies to red blood cells. 00:05:02.810 --> 00:05:05.813 So on the top image we can see if we look at the chromatin structure, 00:05:06.022 --> 00:05:10.943 you can see that immature cell on the left has the loose open chromatin. 00:05:10.943 --> 00:05:13.821 And as the cell matures it becomes more dense and clumped. 00:05:13.821 --> 00:05:17.491 And we have in case in this cell now a poorly segmented neutrophil. 00:05:17.783 --> 00:05:21.787 Also notice the overall cell size has decreased since the cell matured. 00:05:22.330 --> 00:05:26.208 The bottom image shows a coloration that changes in the cytoplasm 00:05:26.208 --> 00:05:29.253 as the cell matures from a very blue cytoplasm 00:05:29.545 --> 00:05:32.423 to a more pinkish cytoplasm, in the case of our poorly 00:05:32.423 --> 00:05:36.052 segmented neutrophils and of course, the development of granules that occurs. 00:05:36.385 --> 00:05:41.515 So in and when we look at red blood cells the cell size also decreases. 00:05:41.515 --> 00:05:42.850 The chromatin structure 00:05:42.850 --> 00:05:46.645 becomes more dense and clumped before the nucleus is expelled. 00:05:46.854 --> 00:05:50.691 And then the cytoplasmic color changes from blue of course to a nice red. 00:05:53.235 --> 00:05:53.694 And this is 00:05:53.694 --> 00:05:54.653 showing again an 00:05:54.653 --> 00:05:58.657 image of a normal peripheral blood smear that shows a nice distribution 00:05:58.657 --> 00:06:02.578 of our red blood cells, shows nice size and shape of our cells, 00:06:03.704 --> 00:06:06.999 shows no inclusions, shows a nice area of central pallor 00:06:06.999 --> 00:06:10.002 in our cells, or what I like to call the whites of their eyes. 00:06:10.628 --> 00:06:11.379 And we find. 00:06:11.379 --> 00:06:14.215 So if we look, for instance here, there's a nice 00:06:14.215 --> 00:06:16.342 we have nice areas of central pallor. 00:06:16.342 --> 00:06:18.302 And then of course we have a lymphocyte, 00:06:18.302 --> 00:06:20.513 and then we have poly segmented neutrophil. 00:06:20.513 --> 00:06:22.431 And I want to mention that, 00:06:22.431 --> 00:06:26.185 a nice internal gauge in helping to determine cell size again 00:06:26.185 --> 00:06:31.732 of red cells is to compare to the nucleus of a small mature, lymphocyte. 00:06:31.732 --> 00:06:35.319 And you can tell this is a lymphocyte just barely with some blue cytoplasm. 00:06:35.569 --> 00:06:36.320 Of course, the trick 00:06:36.320 --> 00:06:40.241 always is, is find that small, normal, mature resting lymphocyte 00:06:41.992 --> 00:06:45.037 changes, however, and when we're trying to identify malignant 00:06:45.204 --> 00:06:49.458 cells, it's a it's good to have the basis of what normal looks like. 00:06:49.458 --> 00:06:51.961 And to remember all the criteria I just talked about. 00:06:51.961 --> 00:06:55.297 Because when cells are malignant, changes can occur. 00:06:55.297 --> 00:06:59.593 And these cells tend to have changes that we will not see normally. 00:06:59.718 --> 00:07:03.806 So malignant cells, especially white cells and morphology does change. 00:07:03.889 --> 00:07:08.185 And specific characteristics can be helpful in classifying and defining 00:07:09.145 --> 00:07:11.355 abnormal population of cells. 00:07:11.355 --> 00:07:16.068 So in the case of cellular characteristics the size can be variable 00:07:16.277 --> 00:07:19.780 sometimes or abnormally large or even abnormally small. 00:07:20.364 --> 00:07:22.783 Sometimes we have to think that, 00:07:22.783 --> 00:07:26.370 the cells were all pure, very similar, or have carnality. 00:07:27.204 --> 00:07:30.499 We also see nuclear changes that can occur in malignancies. 00:07:30.499 --> 00:07:32.209 So shape changes are possible too. 00:07:32.209 --> 00:07:34.587 There can be collecting of our cells. 00:07:34.587 --> 00:07:37.006 There can be pseudo pilger hewwitt. 00:07:37.006 --> 00:07:38.883 There can be hypo segmentation. 00:07:38.883 --> 00:07:40.551 Hyper segmentation. 00:07:40.551 --> 00:07:43.554 Multi nuclear parity is possible. 00:07:43.721 --> 00:07:47.349 We can also see chromatin patterns may look more loose and open, 00:07:47.641 --> 00:07:51.228 or may even represent or be similar to megalo 00:07:51.270 --> 00:07:54.356 blast wide looking cells where we have this asynchrony 00:07:54.648 --> 00:07:57.651 in the maturation between the nucleus and the cytoplasm, 00:07:57.860 --> 00:08:00.863 we may see nucleolus that we would not expect to see. 00:08:01.197 --> 00:08:05.451 Sometimes we may see very large nuclei, only a very prominent nucleus Y. 00:08:05.784 --> 00:08:11.457 There can also be other asteroid features that include again, nuclear cytoplasmic 00:08:11.499 --> 00:08:14.668 eggs and greasy increase in mitotic 00:08:14.668 --> 00:08:18.172 cells, numerous changes in the nucleus. 00:08:20.007 --> 00:08:22.510 We may also see cytoplasmic changes. 00:08:22.510 --> 00:08:23.844 We could see our rods. 00:08:23.844 --> 00:08:28.307 We can see mixed granulation where you'll see basal silicon eosinophilic granules. 00:08:28.724 --> 00:08:31.060 There can be hypo granulation. 00:08:31.060 --> 00:08:33.103 And then the cells may also be more fragile. 00:08:33.103 --> 00:08:36.106 And we could tend to see smudging that is present. 00:08:36.148 --> 00:08:40.277 So I want to mention these characteristics that are possible 00:08:40.277 --> 00:08:44.365 in our malignant cells or abnormal cells as we move forward into our case studies. 00:08:44.782 --> 00:08:47.785 But also keep in mind what is normal. 00:08:49.036 --> 00:08:52.039 Then finally we can also assess platelets 00:08:52.164 --> 00:08:56.335 and have to think in terms of platelet size and numbers. 00:08:56.502 --> 00:09:02.049 And I want to, make a point here with the image on the right is showing 00:09:02.216 --> 00:09:04.009 not only our normal distribution of red cells, 00:09:04.009 --> 00:09:06.762 but we have some nice normal small platelets. 00:09:06.762 --> 00:09:08.806 Here's a platelet overlying a red cell. 00:09:08.806 --> 00:09:09.723 But on the left. 00:09:09.723 --> 00:09:13.602 Now we have what would be considered a giant platelet. 00:09:13.852 --> 00:09:15.396 And we use the term giant. 00:09:15.396 --> 00:09:19.483 If the platelet is as big or bigger than a red blood cell. 00:09:19.483 --> 00:09:22.611 And you can see in this case that it is definitely giant. 00:09:22.861 --> 00:09:26.574 Now the term enlarged is used if we just have a platelet 00:09:26.574 --> 00:09:31.745 that is smaller than the giant but bigger than the normal that we would see. 00:09:32.246 --> 00:09:34.707 But it's important to also evaluate our platelets. 00:09:37.585 --> 00:09:38.002 All right. 00:09:38.002 --> 00:09:40.379 At this point we're ready for our first case. 00:09:40.379 --> 00:09:43.882 Case one an 88 year old female is brought 00:09:43.882 --> 00:09:47.303 to the emergency room by her son after fall in her apartment. 00:09:47.886 --> 00:09:50.889 In addition to hip pain, she complains of cramping 00:09:51.307 --> 00:09:54.393 and abdominal discomfort associated with episodes of mild 00:09:54.393 --> 00:09:57.730 to moderate diarrhea that has persisted for several days. 00:09:58.188 --> 00:10:00.608 She is feverish and disoriented. 00:10:00.608 --> 00:10:03.861 The history will be important, and what information 00:10:03.861 --> 00:10:06.864 from clinical presentation might be significant. 00:10:06.989 --> 00:10:09.908 And I think in this particular case, 00:10:09.908 --> 00:10:13.912 you should hone in on the age of the patient and the clinical symptom 00:10:13.912 --> 00:10:18.917 of her, abdominal discomfort, cramping, diarrhea that could be significant. 00:10:19.501 --> 00:10:22.129 She's also has some fever and disorientation. 00:10:22.129 --> 00:10:27.384 And then from her CBC, I encourage you to consider what parameters 00:10:28.636 --> 00:10:30.387 are abnormal here. And 00:10:31.639 --> 00:10:34.642 whenever I look at results 00:10:34.683 --> 00:10:37.770 from a complete blood count, I always start at the top 00:10:38.312 --> 00:10:41.023 with my white count and kind of work my way down. 00:10:41.023 --> 00:10:44.860 And then when I come to the red cell related parameters 00:10:44.902 --> 00:10:47.905 h and h, I look for the rule of three. 00:10:47.905 --> 00:10:51.617 Okay, that my hematocrit is approximately three times my hemoglobin. 00:10:51.950 --> 00:10:56.330 The hemoglobin is approximately three times the red blood cell count. 00:10:56.330 --> 00:10:58.874 I look to see if the indices are normal. 00:10:58.874 --> 00:11:02.169 I assess the platelet count and then I move forward down 00:11:02.169 --> 00:11:05.172 into differential results. 00:11:06.298 --> 00:11:07.716 So in this case 00:11:07.716 --> 00:11:10.719 I think you should note of course the elevated white count. 00:11:11.345 --> 00:11:14.264 There is a slight anemia in this patient. 00:11:14.264 --> 00:11:17.810 And there's definitely a shift to the left with her neutrophils. 00:11:19.853 --> 00:11:22.147 So if we look at one of the images 00:11:23.565 --> 00:11:24.108 now I'm going to 00:11:24.108 --> 00:11:27.111 interject a disclaimer here as we move forward. 00:11:27.111 --> 00:11:32.866 Because I'm not going to show multiple multiple multiple images from each case. 00:11:32.866 --> 00:11:36.578 So I typically have 2 to 3 images for each case. 00:11:36.578 --> 00:11:40.666 But as we all know of course it's important to assess multiple fields 00:11:40.666 --> 00:11:43.460 when we're looking and scanning through our peripheral blood smear. 00:11:43.460 --> 00:11:47.131 But in the interest of time, I can't I can't show too many. 00:11:47.423 --> 00:11:50.426 But note this is one image 00:11:50.634 --> 00:11:53.595 and here is another image. 00:11:53.595 --> 00:11:57.307 Case one polling question which of the following 00:11:57.307 --> 00:12:00.352 is the most likely explanation of this woman's condition? 00:12:02.020 --> 00:12:04.732 Chronic myelogenous leukemia. 00:12:04.732 --> 00:12:07.192 Chronic neutrophil like leukemia. 00:12:07.192 --> 00:12:09.194 Fulminant infection. 00:12:09.194 --> 00:12:12.197 Myelodysplastic syndrome. 00:12:14.783 --> 00:12:16.076 For case one, 00:12:16.076 --> 00:12:19.121 the correct answer is fulminant infection. 00:12:19.121 --> 00:12:21.206 So let's 00:12:21.206 --> 00:12:22.833 move on. And I want you to think about 00:12:22.833 --> 00:12:26.211 a couple additional questions now as I move forward. 00:12:26.420 --> 00:12:29.298 And I think as as I mentioned, 00:12:29.298 --> 00:12:32.342 the white blood count being, 00:12:33.594 --> 00:12:34.428 elevated is 00:12:34.428 --> 00:12:37.639 something that should be considered 00:12:37.639 --> 00:12:41.393 and certainly would be unexpected in someone that had just an infection. 00:12:41.685 --> 00:12:45.355 And so we certainly do want to consider leukemia in this case, 00:12:45.355 --> 00:12:49.067 both the chronic myelogenous leukemia and chronic neutrophil like leukemia. 00:12:49.651 --> 00:12:53.572 Now, with chronic myelogenous leukemia, we would expect 00:12:53.572 --> 00:12:57.618 to see an increase, however, perhaps in eosinophils in basa cells, 00:12:57.951 --> 00:13:01.580 we may see more evidence of earlier immaturity. 00:13:01.580 --> 00:13:06.668 That is pro myocytes in mild sites and maybe were reported in this, case. 00:13:07.127 --> 00:13:11.340 The age of patient is also very unusual for someone that would present 00:13:11.340 --> 00:13:16.136 with a chronic myelogenous leukemia, because this is a malignancy 00:13:16.136 --> 00:13:21.934 that presents in patients that are in the 40 to 50 year age range. 00:13:22.518 --> 00:13:25.771 I would also say it's unlikely that this would be a chronic neutrophil 00:13:25.771 --> 00:13:26.688 like leukemia. 00:13:26.688 --> 00:13:30.317 This is a rare disorder, and there are less 00:13:30.317 --> 00:13:33.570 than 150 cases that have yet to be present, 00:13:33.946 --> 00:13:37.699 reported under the new classification with the World Health Organization. 00:13:38.033 --> 00:13:41.745 And clinically, we would expect to see more hematoma 00:13:41.745 --> 00:13:47.209 polynomially in the case of leukemias, which this patient did not have yet. 00:13:47.835 --> 00:13:51.880 With a severe infection, we would expect to see perhaps doli 00:13:51.880 --> 00:13:55.843 bodies, vacuole, some toxic granulation, which we did not see. 00:13:56.677 --> 00:13:59.847 Now, additional tests certainly are going to be necessary 00:13:59.847 --> 00:14:02.558 to help to confirm the diagnosis. 00:14:02.558 --> 00:14:06.979 And in this case, because of the clinical presentation with the abdominal cramping, 00:14:06.979 --> 00:14:10.107 the diarrhea, stool cultures were performed. 00:14:10.983 --> 00:14:13.986 And interestingly enough, okay, 00:14:14.236 --> 00:14:19.283 this patient turned out to have Clostridium difficile infection. 00:14:19.700 --> 00:14:24.580 And it was a fulminant Life-Threatening colitis that she developed. 00:14:24.580 --> 00:14:28.125 She actually, had an ileostomy performed 00:14:28.584 --> 00:14:33.005 and did survive, but had a very fulminant infection. 00:14:33.005 --> 00:14:36.550 So this was a very unusual presentation for a C diff 00:14:37.050 --> 00:14:41.471 in that the white count was so high and was was, 00:14:43.098 --> 00:14:46.101 elevated enough that a malignancy was considered. 00:14:46.518 --> 00:14:50.147 Now, a couple comments about C diff, colitis 00:14:50.147 --> 00:14:55.444 and this occurs when there's disruption of the normal bacteria flora in the colon. 00:14:56.028 --> 00:15:01.033 And the colonization of the C diff releases toxins that caused mucosal damage 00:15:01.033 --> 00:15:04.453 and inflammation and result in the severe diarrhea that can occur. 00:15:04.912 --> 00:15:06.955 Major risk factor is exposure. 00:15:06.955 --> 00:15:11.627 Prior exposure to antibiotics such as cephalosporins and ampicillin. 00:15:11.627 --> 00:15:14.671 Some OXA cell in the advanced age of patients 00:15:14.671 --> 00:15:18.467 is also a risk factor, as is hospitalization. 00:15:19.176 --> 00:15:23.722 Now, in this particular case, this case was based off of my mother in law, 00:15:24.097 --> 00:15:26.975 and she was not hospitalized prior to this. 00:15:26.975 --> 00:15:30.437 But she did live in, assisted living. 00:15:31.021 --> 00:15:34.274 And that is has been reported to be. 00:15:34.274 --> 00:15:38.445 In fact, the centers for Disease Control and Prevention have noted that 94% of C 00:15:38.445 --> 00:15:43.033 diff infections have been related to medical care, with 25% 00:15:43.033 --> 00:15:48.997 among hospital patients, 75% among nursing home patients and patients, 00:15:49.039 --> 00:15:52.584 or potentially also that have been seen in doctor's offices. 00:15:52.918 --> 00:15:55.921 And so while I don't know, for sure, 00:15:55.921 --> 00:15:59.299 this is suspected that this is where my mother in law developed that. 00:15:59.299 --> 00:16:03.553 But you can imagine my concern when I saw the 80,000 white count. 00:16:04.429 --> 00:16:08.183 And so mixed relief, I guess, when it was, a C diff. 00:16:08.934 --> 00:16:13.605 Now, just for comparison, here is someone with a chronic myelogenous leukemia, 00:16:13.605 --> 00:16:18.944 and you can see here l can also see from the side up about 1:00. 00:16:19.277 --> 00:16:22.280 And, I lost sight over, 00:16:22.280 --> 00:16:24.741 in the other over this way. 00:16:27.077 --> 00:16:31.164 So, just something to, compare. 00:16:34.793 --> 00:16:35.252 All right. 00:16:35.252 --> 00:16:37.087 Our next case. 00:16:37.087 --> 00:16:42.342 Case two, a 77 year old man visits his family physician 00:16:42.592 --> 00:16:45.345 for evaluation of consistent weight loss 00:16:45.345 --> 00:16:48.181 fever, fatigue, and malaise. 00:16:48.181 --> 00:16:50.142 He appears pale and a physician. 00:16:50.142 --> 00:16:52.644 Notes marked spinal. Magli. 00:16:52.644 --> 00:16:55.022 Note the clinical symptoms 00:16:55.022 --> 00:16:58.025 that are significant. 00:16:58.859 --> 00:17:01.862 And here are the CBC results. 00:17:02.362 --> 00:17:05.365 Starting at the top and working down, we can see that there is 00:17:06.408 --> 00:17:08.535 an elevated white count, although not as extreme 00:17:08.535 --> 00:17:13.373 as what we just saw in the first case, maybe a slight anemia for a male platelet 00:17:13.373 --> 00:17:16.376 counts a little bit on the lower side, although not critical. 00:17:17.627 --> 00:17:20.630 We do have an increase in neutrophils. 00:17:22.174 --> 00:17:24.801 And somewhat of a left shift 00:17:24.801 --> 00:17:27.804 and then an increase in monocytes. 00:17:28.638 --> 00:17:31.516 Here is one image. 00:17:31.516 --> 00:17:32.350 The peripheral blood. 00:17:33.477 --> 00:17:36.480 And I would note this cell 00:17:36.563 --> 00:17:40.192 that almost looks hyper segmented certainly has several lobes. 00:17:40.192 --> 00:17:42.611 And then we have some nice monocytes. 00:17:42.611 --> 00:17:44.905 This one 00:17:44.905 --> 00:17:47.574 some lobes as well. 00:17:47.574 --> 00:17:50.535 Here's another image showing immature 00:17:51.745 --> 00:17:52.829 neutrophils on the right. 00:17:52.829 --> 00:17:55.832 On my left side. 00:17:57.542 --> 00:17:57.793 Okay. 00:17:57.793 --> 00:18:01.338 So now we're going to think about our second polling question. 00:18:02.839 --> 00:18:05.550 Case two polling question. 00:18:05.550 --> 00:18:08.512 What is the most probable diagnosis of this patient's 00:18:08.512 --> 00:18:11.515 disorder myelodysplastic syndrome. 00:18:11.723 --> 00:18:14.476 Chronic mild Manistique leukemia. 00:18:14.476 --> 00:18:17.020 Chronic myelogenous leukemia. 00:18:17.020 --> 00:18:20.023 Benign monocyte ptosis. 00:18:21.233 --> 00:18:23.026 The answer to case two polling 00:18:23.026 --> 00:18:26.488 question is chronic Milo Manistique leukemia 00:18:27.531 --> 00:18:27.739 okay. 00:18:27.739 --> 00:18:31.118 Some additional questions that will be addressed okay. 00:18:31.118 --> 00:18:35.372 So it's important to look at the morphology of the cells 00:18:35.705 --> 00:18:39.543 in this case the monocytes but also the neutrophils. 00:18:39.918 --> 00:18:43.255 And that there certainly were additional tests that were necessary 00:18:43.338 --> 00:18:46.925 to help define define this particular condition. 00:18:49.094 --> 00:18:52.097 This was actually 00:18:52.222 --> 00:18:55.892 a case of a chronic Milo City leukemia. 00:18:56.685 --> 00:19:01.314 And when we talk about describing morphology of cells again, I take you back 00:19:01.314 --> 00:19:06.069 to what I described in the first few slides in regards to overall cell size, 00:19:06.319 --> 00:19:09.322 nuclear features, and cytoplasmic characteristics. 00:19:09.865 --> 00:19:15.287 And I noted, on the one image that we saw, the hyper segmented cells. 00:19:15.287 --> 00:19:17.539 So that was of particular note. 00:19:17.539 --> 00:19:22.085 Now the patient's clinical presentation and laboratory findings do both suggest 00:19:22.085 --> 00:19:26.089 not only a mild dysplastic syndrome because we have some evidence of that, 00:19:27.132 --> 00:19:30.135 but also mild proliferative neoplasm. 00:19:30.260 --> 00:19:34.055 The World Health Organization classification of hematologic malignancies 00:19:34.055 --> 00:19:38.310 includes a group of disorders that actually overlap 00:19:38.310 --> 00:19:41.688 both these conditions, and it is called the Milo dysplastic syndrome. 00:19:41.688 --> 00:19:44.691 Slash Milo proliferative neoplasms 00:19:44.774 --> 00:19:48.236 and chronic Milo Manistique leukemia falls in this category. 00:19:48.236 --> 00:19:50.113 This particular category 00:19:50.113 --> 00:19:54.951 patients with this category have effective cellular proliferation, so we can see 00:19:54.951 --> 00:19:59.164 an increase in cell counts as we did in this example the white cell count. 00:19:59.539 --> 00:20:02.626 But then they also have some evidence of dysplasia. 00:20:04.127 --> 00:20:05.629 They also because of this 00:20:05.629 --> 00:20:09.591 dysplasia sometimes present with cytokines in other cell lines. 00:20:09.716 --> 00:20:12.636 So I remind you that the white count or excuse me, 00:20:12.636 --> 00:20:15.639 the platelet count was slightly normal or slightly low. 00:20:15.805 --> 00:20:18.767 And the the agent age was slightly low. 00:20:18.808 --> 00:20:21.728 In this particular patient example, 00:20:21.728 --> 00:20:25.148 the laboratory findings result in these conditions because we have 00:20:25.148 --> 00:20:28.735 abnormalities in the regulation, the myeloid proliferation 00:20:29.486 --> 00:20:31.905 and survival of these cells. 00:20:31.905 --> 00:20:34.908 Now, not only is there chronic Milo monosyllabic 00:20:35.033 --> 00:20:38.161 leukemia in this classification, there's also atypical 00:20:38.536 --> 00:20:41.289 chronic, chronic myelogenous leukemia. 00:20:41.289 --> 00:20:44.209 That means there is a Philadelphia chromosome negative. 00:20:44.209 --> 00:20:47.837 There is juvenile monomials, city leukemia, 00:20:48.296 --> 00:20:51.925 and then unclassified category of MDS, MMP. 00:20:51.925 --> 00:20:55.720 And now we can rule out the juvenile Mono 00:20:56.263 --> 00:20:58.932 City leukemia based on the patient's age. 00:20:58.932 --> 00:21:02.185 It's also unlikely that there is a benign monocyte ptosis 00:21:02.185 --> 00:21:07.023 in this patient because of the slight anemia, the decrease in the platelet count 00:21:07.274 --> 00:21:12.862 that are present and that we would also see, not see the unusual morphology 00:21:13.029 --> 00:21:16.825 that we did see in some of the neutrophils as with this hyper segmentation. 00:21:17.325 --> 00:21:19.035 So now we're down to distinguishing 00:21:19.035 --> 00:21:22.706 between chronic myelogenous leukemia and the CML. 00:21:22.914 --> 00:21:25.709 And this is where additional tests will become useful. 00:21:25.709 --> 00:21:28.712 So Philadelphia chromosome will be positive 00:21:28.712 --> 00:21:30.880 at the BCR travel gene rearrangement. 00:21:30.880 --> 00:21:32.549 Of course if it's CML 00:21:33.883 --> 00:21:37.345 now we can see some types of dysplasia in CML. 00:21:37.345 --> 00:21:42.058 But it's not near as prominent as we might see in CML. 00:21:42.559 --> 00:21:45.979 What really defines this is the 20% monocytes. 00:21:46.354 --> 00:21:49.899 And that is a criteria for 00:21:50.442 --> 00:21:55.572 when we look at the absolute count for CML that would define this as a monocyte, 00:21:56.239 --> 00:21:59.242 a CML. 00:21:59.576 --> 00:22:03.413 Now when we look at evidences of some dysplasia, 00:22:03.413 --> 00:22:06.791 a couple of things I want to point out in this particular example. 00:22:07.500 --> 00:22:10.545 So if we look at this neutrophil first of all we can see 00:22:11.212 --> 00:22:14.424 a very unusual nuclear shape almost a ring. 00:22:14.424 --> 00:22:16.343 Although I think there is a division here. 00:22:16.343 --> 00:22:18.219 So this still is perhaps a band. 00:22:18.219 --> 00:22:22.223 But notice the hypo granularity in this particular cell. 00:22:22.849 --> 00:22:26.227 Notice here in this neutrophil it looks like 00:22:26.311 --> 00:22:28.605 I've stopped shy of calling it a delivery. 00:22:28.605 --> 00:22:29.731 I don't really think it is, 00:22:29.731 --> 00:22:32.692 but it looks like some kind of abnormal granulation there. 00:22:32.692 --> 00:22:36.112 Now our neutrophils are showing in some dysplasia 00:22:36.112 --> 00:22:40.408 which is finding commonly in CML. 00:22:40.658 --> 00:22:43.787 We have however the increase in all the monocytes 00:22:43.953 --> 00:22:47.665 which do define this as a CML. 00:22:47.749 --> 00:22:48.833 So according to the World 00:22:48.833 --> 00:22:52.420 Health Organization we need a persistent peripheral blood monocyte ptosis 00:22:52.712 --> 00:22:56.841 greater than 1.0 times ten to the nine per liter to define this condition. 00:22:56.841 --> 00:23:01.513 Also notice this neutrophil on the left also looks slightly hypo granular. 00:23:01.554 --> 00:23:04.682 So these granularity the lack of granules in these cells 00:23:04.682 --> 00:23:06.726 are clear dysplastic features. 00:23:06.726 --> 00:23:09.187 Now the monocytes can also show dysplasia too. 00:23:09.187 --> 00:23:12.649 I don't have an image that shows that in this particular case. 00:23:12.649 --> 00:23:16.194 But we can see sometimes darker cytoplasmic 00:23:16.194 --> 00:23:19.155 BSA philia as one of the dysplastic changes. 00:23:19.406 --> 00:23:21.699 But this just emphasizes how important it is 00:23:21.699 --> 00:23:24.411 to have a good peripheral blood smear with a good stain. 00:23:24.411 --> 00:23:25.787 Good distribution of cells. 00:23:25.787 --> 00:23:27.622 When you're looking for dysplasia. 00:23:30.917 --> 00:23:31.126 Okay. 00:23:31.126 --> 00:23:34.129 Our next case case for 00:23:34.796 --> 00:23:37.757 our Caucasian male in his early 30s, presented 00:23:37.757 --> 00:23:41.469 at the emergency room with a nosebleed that could not be controlled. 00:23:42.095 --> 00:23:45.014 He reported that similar episodes of Epistaxis 00:23:45.014 --> 00:23:47.058 occurred throughout his childhood. 00:23:47.058 --> 00:23:49.978 Once, when he was a toddler, his parents panicked 00:23:49.978 --> 00:23:53.606 when mucosal bleeding became so severe it could not be stopped. 00:23:54.190 --> 00:23:57.068 They took him to the hospital, where he received 00:23:57.068 --> 00:24:00.071 a blood transfusion. 00:24:00.113 --> 00:24:02.907 He did not need any transfusions in high school, 00:24:02.907 --> 00:24:05.910 but he was not permitted to play any contact sports. 00:24:06.494 --> 00:24:09.289 His bleeding episodes resumed after high school, 00:24:09.289 --> 00:24:12.167 and he has been transfusion dependent ever since. 00:24:12.167 --> 00:24:15.170 The only platelets are usually transfused now. 00:24:15.253 --> 00:24:17.839 In one year he received five transfusions 00:24:17.839 --> 00:24:20.842 to support an uncontrolled bleeding event. 00:24:21.050 --> 00:24:24.804 The family history is negative and no other relatives are affected. 00:24:25.597 --> 00:24:29.642 So now I hope you're picking up on the bleeding tendency here. 00:24:31.144 --> 00:24:34.147 And then his CBC. 00:24:34.981 --> 00:24:38.276 And again, if we start at the top of the results and work our way 00:24:38.276 --> 00:24:42.238 down, I think you'll find something quite significant when you get to platelets. 00:24:44.365 --> 00:24:47.327 The differential count was unremarkable 00:24:47.327 --> 00:24:50.330 as far as white blood cell count, 00:24:50.788 --> 00:24:53.666 so I did not list those. 00:24:53.666 --> 00:24:55.585 But if we look at the image, 00:24:55.585 --> 00:24:58.546 here's first image. 00:25:04.594 --> 00:25:07.597 Here's second image. 00:25:12.936 --> 00:25:13.186 Okay. 00:25:13.186 --> 00:25:16.189 So now we're ready for our next polling question. 00:25:17.482 --> 00:25:20.109 Case for polling question. 00:25:20.109 --> 00:25:24.322 What are the abnormal findings seen in the images of the peripheral blood 00:25:25.240 --> 00:25:28.243 thrombocytopenia and large platelets. 00:25:28.493 --> 00:25:31.496 Thrombocytopenia and normal platelets 00:25:31.579 --> 00:25:35.708 a ptosis and psychosis microsite. 00:25:35.708 --> 00:25:38.711 Ptosis and hypokalemia. 00:25:42.173 --> 00:25:42.715 The answer 00:25:42.715 --> 00:25:46.010 for the case for polling question is thrombocytopenia. 00:25:46.636 --> 00:25:49.639 Large platelets. 00:25:50.598 --> 00:25:54.852 This is a case of something that was very rare. 00:25:55.353 --> 00:25:57.981 And of course, the what we're seeing here 00:25:57.981 --> 00:26:02.151 are the enlarged platelets that help really define this condition. 00:26:03.736 --> 00:26:04.070 I was 00:26:04.070 --> 00:26:08.241 pretty excited, actually, when a program graduate 00:26:08.241 --> 00:26:11.786 contacted me that she had married a man with this condition. 00:26:12.412 --> 00:26:17.333 I thought it was pretty cool to be able to include this in presentations. 00:26:17.709 --> 00:26:20.712 This is a rare autosomal recessive disorder, 00:26:21.004 --> 00:26:25.383 and by rare I mean less than or about 1 in 1,000,000 individuals. 00:26:25.383 --> 00:26:28.386 And it's called Bernard Sawyer syndrome. 00:26:28.428 --> 00:26:32.890 And this condition is characterized by the abnormal, 00:26:33.683 --> 00:26:36.644 an abnormal glycoprotein in the platelets, or even sometimes 00:26:36.644 --> 00:26:40.398 the absence of a glycoprotein is called platelet glycoprotein 00:26:40.398 --> 00:26:43.401 one b, glycoprotein one b. 00:26:43.401 --> 00:26:47.280 It facilitates the binding of platelets with von Willebrand factor 00:26:47.572 --> 00:26:51.534 and allows the platelets to adhere to exposed sub endothelial tissue. 00:26:51.743 --> 00:26:54.954 When a vessel was breached, our platelet aggregation 00:26:55.705 --> 00:26:59.083 is an important test that's going to define this condition. 00:26:59.459 --> 00:27:01.794 There's abnormal response to risk to Seton, 00:27:01.794 --> 00:27:05.214 and that abnormal response in platelet aggregation is not corrected. 00:27:05.423 --> 00:27:09.260 When we add either risk to Seton or von Willebrand factor 00:27:09.594 --> 00:27:13.389 aggregation with other agonists like ATP, collagen are going to be normal 00:27:14.057 --> 00:27:19.020 because the platelet membrane is attached to the platelet cytoskeleton 00:27:19.228 --> 00:27:23.316 using or via glycoprotein one B, there can be loss of normal 00:27:23.316 --> 00:27:26.694 membrane cytoskeletal function, and that's what accounts 00:27:26.694 --> 00:27:29.697 for the abnormal platelet morphology. 00:27:29.739 --> 00:27:32.492 In Bernards, CVA patients, 00:27:32.492 --> 00:27:36.496 around 60 to 80% of the platelets are going to be increased in size. 00:27:36.496 --> 00:27:39.082 So we'll see an mikveh that is elevated. 00:27:39.082 --> 00:27:41.459 Now the condition arises. 00:27:41.459 --> 00:27:46.172 As I said, it's an autism recessive, which means that the person the patient 00:27:46.172 --> 00:27:51.427 has to inherit one gene from each parent in order to be symptomatic. 00:27:51.427 --> 00:27:53.971 So heterozygotes are going to be asymptomatic. 00:27:53.971 --> 00:27:57.058 Homozygote are going to have lifelong bleeding tendencies 00:27:57.350 --> 00:27:59.727 that actually begin in infancy. 00:27:59.727 --> 00:28:02.897 Now, this can occur as a spontaneous gene mutation. 00:28:03.147 --> 00:28:05.692 And of course, that's not very common as well. 00:28:06.901 --> 00:28:08.736 So another image, 00:28:08.736 --> 00:28:11.989 I would think that in this case this is a platelet 00:28:11.989 --> 00:28:15.743 over here is certainly pretty close to being giant as well. 00:28:15.743 --> 00:28:17.203 So and if we compare 00:28:17.203 --> 00:28:20.707 to the red cells that are adjacent to it now we do see some normal platelets. 00:28:20.957 --> 00:28:23.334 I think over here we have more enlarged platelets. 00:28:23.334 --> 00:28:24.961 So certainly there are large platelets. 00:28:24.961 --> 00:28:29.048 But what is clinically significant are seeing the thrombocytopenia 00:28:29.841 --> 00:28:32.385 along with the enlarged platelets. 00:28:32.385 --> 00:28:35.388 And so the presentation in this case 00:28:35.430 --> 00:28:39.475 with the peripheral blood smear shows evidence of Bernhard CVA. 00:28:39.475 --> 00:28:40.393 And then of course 00:28:40.393 --> 00:28:44.480 clinically with the lifelong bleeding that this patient has experienced. 00:28:45.064 --> 00:28:47.233 So I was thankful to our graduate. 00:28:47.233 --> 00:28:49.277 She was, her poor husband. 00:28:49.277 --> 00:28:52.905 He was very, very good about this and came in and let me draw his blood and, 00:28:53.573 --> 00:28:55.158 I'm asking a bunch of questions. 00:28:57.076 --> 00:28:57.285 Okay. 00:28:57.285 --> 00:28:59.537 Let's move on to our next case. 00:28:59.537 --> 00:29:01.122 Case seven. 00:29:01.122 --> 00:29:04.834 An eight year old African-American girl was brought to her physician 00:29:05.001 --> 00:29:08.004 for evaluation of right upper quadrant pain. 00:29:08.504 --> 00:29:11.507 She has a lifelong history of hemolytic anemia. 00:29:11.966 --> 00:29:14.510 So I think, significantly here 00:29:14.510 --> 00:29:18.347 we have a child that already has described 00:29:18.347 --> 00:29:21.350 as a lifelong history of anemia, 00:29:21.976 --> 00:29:24.979 and her results. 00:29:26.147 --> 00:29:27.648 And if we start at the top 00:29:27.648 --> 00:29:31.194 and work our way down and results, we can see that 00:29:31.736 --> 00:29:34.697 she does have some anemia. 00:29:35.031 --> 00:29:38.034 And I will draw your attention to the indices 00:29:38.326 --> 00:29:41.329 in this case with a low MCV, low 00:29:41.454 --> 00:29:44.457 and slightly elevated mixie. 00:29:45.750 --> 00:29:48.753 And if we look at peripheral blood. 00:29:50.797 --> 00:29:53.800 I hope you're saying wow. 00:29:54.217 --> 00:29:57.220 Or thinking wow. 00:29:59.806 --> 00:30:02.809 And another image. 00:30:04.101 --> 00:30:07.396 And of course I didn't capture any white blood cells, but they were normal. 00:30:07.563 --> 00:30:11.526 And we're certainly focusing in on all of this red cell morphology. 00:30:14.403 --> 00:30:14.570 Okay. 00:30:14.570 --> 00:30:18.449 So now we're ready for our next polling question. 00:30:19.325 --> 00:30:21.744 K7 polling question. 00:30:21.744 --> 00:30:23.913 Which of the following is the most likely 00:30:23.913 --> 00:30:26.916 explanation of this child's condition? 00:30:27.291 --> 00:30:29.752 Hereditary Spiro psychosis. 00:30:29.752 --> 00:30:32.213 Hemolytic uremic syndrome. 00:30:32.213 --> 00:30:34.924 Hereditary and lepto psychosis. 00:30:34.924 --> 00:30:37.927 Hereditary pyro piccolo psychosis. 00:30:40.805 --> 00:30:42.473 The answer to the k seven 00:30:42.473 --> 00:30:46.894 polling question is hereditary pyro piccolo psychosis. 00:30:48.104 --> 00:30:52.817 And as you can see on the image put up, there is clearly some evidence 00:30:52.817 --> 00:30:56.279 of sphere sites that are present, as well as fragmented cells. 00:30:56.487 --> 00:31:00.825 That would lead one to think that we might have a hemolytic uremic syndrome. 00:31:01.075 --> 00:31:02.451 Here is, 00:31:02.451 --> 00:31:05.454 a sphere of sight, maybe a little tail here. 00:31:05.496 --> 00:31:08.499 And we certainly see some evidence of fragmentation. 00:31:09.709 --> 00:31:13.546 And the sites in particular tend to be more, triangular. 00:31:13.546 --> 00:31:15.047 So one over here, the. Right. 00:31:15.047 --> 00:31:18.801 So there are also some elliptic sites that are present. 00:31:22.054 --> 00:31:23.890 But this is actually 00:31:23.890 --> 00:31:28.519 an example of a hereditary pyro point glow psychosis. 00:31:28.936 --> 00:31:32.565 This striking red cell morphology with the budding, 00:31:32.565 --> 00:31:33.774 the fragments, the sphere 00:31:33.774 --> 00:31:37.570 sites, the elliptic sites even some of the cells that have little tails on them. 00:31:37.570 --> 00:31:39.739 If we look at the red cell down here, notice 00:31:39.739 --> 00:31:42.950 this little tail out on this particular red cell. 00:31:43.492 --> 00:31:48.247 So this is very classic presentation for an HP. 00:31:48.497 --> 00:31:52.293 Now also could consider 00:31:52.293 --> 00:31:55.796 I did not put this as a choice but a severe burn. 00:31:56.047 --> 00:32:00.259 Except there was nothing in the history that led us to think there might be, 00:32:01.844 --> 00:32:03.512 an acquired condition. 00:32:03.512 --> 00:32:06.557 This was clearly something that was inherited 00:32:07.099 --> 00:32:12.146 now hereditary sphere of psychosis, particularly with a slightly elevated MCQ, 00:32:12.355 --> 00:32:16.275 could be considered, but we don't see really enough sphere sites 00:32:16.525 --> 00:32:20.196 to consider that in the in the event of all or in the face 00:32:20.196 --> 00:32:22.031 of all of the other morphology, 00:32:22.031 --> 00:32:25.534 the fragmentation in the elective situs that is also present. 00:32:26.243 --> 00:32:30.873 The other thing about micro and Pathak hemolytic anemia, like H2, was, 00:32:31.165 --> 00:32:34.543 disseminated intravascular coagulation, thrombotic thrombocytopenia, 00:32:35.419 --> 00:32:39.298 you could also see, some platelets that would be decreased. 00:32:39.298 --> 00:32:42.134 And we did not see that in this particular example. 00:32:42.134 --> 00:32:46.973 And we would not see this striking of the morphology in this case. Now 00:32:48.349 --> 00:32:49.642 to consider 00:32:49.642 --> 00:32:53.396 Spheeris or hereditary lepto psychosis could be also possibility. 00:32:53.646 --> 00:32:56.524 And in actuality HPP is a variant. 00:32:56.524 --> 00:32:58.526 A subtype of electro situs is. 00:32:58.526 --> 00:33:02.113 It's a more severe cousin to the lepto psychosis, but someone 00:33:02.113 --> 00:33:06.784 with a straight hereditary lepto psychosis is not going to have this fragmentation. 00:33:07.576 --> 00:33:11.038 This fear cites this mercy of of of of an appearance. 00:33:11.580 --> 00:33:14.083 HBP is a rare hemolytic anemia. 00:33:14.083 --> 00:33:17.503 Again, it is autosomal recessive and as I mentioned, is closely 00:33:17.503 --> 00:33:21.173 related to hemolytic or hereditary electro sight ptosis. 00:33:21.173 --> 00:33:23.926 It is seen in African-Americans. 00:33:23.926 --> 00:33:25.970 But it's been diagnosed also 00:33:25.970 --> 00:33:29.056 in Caucasians and other populations. 00:33:29.724 --> 00:33:34.979 The HPP cells actually have two defects, one that's inherited from each parent. 00:33:34.979 --> 00:33:39.025 So one parent has, passes along a defect 00:33:39.025 --> 00:33:44.030 that allows spectrum to be, abnormal in the membrane. 00:33:44.030 --> 00:33:48.367 And the other parent sends along, a defect in how the spectrum 00:33:48.367 --> 00:33:51.787 is attaching to the cytoskeletal structure of the membrane. 00:33:51.954 --> 00:33:55.624 And so these patients, then their cells literally are torn apart, 00:33:56.292 --> 00:33:58.878 through shear stresses in the circulation. 00:34:00.921 --> 00:34:02.465 The similarities of these red 00:34:02.465 --> 00:34:08.512 cells in HPP to those, that looked like, someone that has had a thermal injury 00:34:08.512 --> 00:34:14.060 or burn led investigators to examine the thermal sensitivity of cells. 00:34:14.060 --> 00:34:17.646 And then indeed, they do have increased sensitivity under heat. 00:34:17.688 --> 00:34:22.068 Normal red cells are going to fragment around 49 to 50°C, 00:34:22.068 --> 00:34:26.739 whereas HPP cells will fragment around 45 to 46 degrees cells. 00:34:26.739 --> 00:34:30.868 So it's just an additional, information that's noted. 00:34:31.786 --> 00:34:35.539 Mcvie's can be decreased in the HPP patient 00:34:35.539 --> 00:34:38.834 because of the severe fragmentation that occurs in these cells. 00:34:38.834 --> 00:34:40.878 So very interesting condition. 00:34:40.878 --> 00:34:44.048 This was a patient that did come to University 00:34:44.423 --> 00:34:47.301 of Utah, Medical Center and, 00:34:47.301 --> 00:34:50.304 and was evaluated. 00:34:50.596 --> 00:34:50.805 Okay. 00:34:50.805 --> 00:34:53.307 Our next case, 00:34:53.307 --> 00:34:55.101 case eight, 00:34:55.101 --> 00:34:58.145 a 28 year old man suffers from persistent 00:34:58.145 --> 00:35:01.565 and chronic diarrhea of approximately two months duration. 00:35:02.691 --> 00:35:03.067 He has 00:35:03.067 --> 00:35:06.320 also experienced abdominal cramps, fatigue, and weight loss. 00:35:06.946 --> 00:35:10.157 He is a medical laboratory scientist and performs a CBC 00:35:10.324 --> 00:35:13.327 as a first step in the evaluation of his disorder. 00:35:14.787 --> 00:35:17.790 Here are his results. 00:35:18.457 --> 00:35:20.751 And one thing, 00:35:20.751 --> 00:35:23.587 of note as you look at the results, 00:35:23.587 --> 00:35:26.674 is that, his age looked pretty good, 00:35:27.842 --> 00:35:31.011 but he does look like he has a micro stick. 00:35:31.554 --> 00:35:34.557 Perhaps hyper chromic anemia. 00:35:35.808 --> 00:35:38.644 Although H and H are not yet decreased. 00:35:38.644 --> 00:35:41.814 I will comment that this condition develops in stages, 00:35:42.022 --> 00:35:45.025 so the indices may be decreased 00:35:45.442 --> 00:35:48.529 prior to the hemoglobin a hematocrit decreasing. 00:35:48.863 --> 00:35:51.782 So if we look at, 00:35:51.782 --> 00:35:54.535 example, the peripheral blood smear 00:35:54.535 --> 00:35:58.080 and the lymphocyte is there, our normal resting lymphocyte 00:35:59.832 --> 00:36:02.543 to help you compare size. 00:36:02.543 --> 00:36:07.131 And I will also note the cell up here about 2:00 ish 00:36:08.632 --> 00:36:08.841 here. 00:36:08.841 --> 00:36:11.844 Here's another image of the peripheral blood. 00:36:12.261 --> 00:36:14.930 Here's another slightly 00:36:14.930 --> 00:36:17.391 oval ish cell up there. 00:36:17.391 --> 00:36:19.768 Case eight pulling question 00:36:19.768 --> 00:36:23.272 what is the most probable diagnosis of this man's disorder? 00:36:24.064 --> 00:36:25.941 Lead poisoning. 00:36:25.941 --> 00:36:28.277 Anemia of chronic disease. 00:36:28.277 --> 00:36:30.613 Iron deficiency anemia. 00:36:30.613 --> 00:36:33.616 Heterozygous beta thalassemia. 00:36:36.869 --> 00:36:39.705 The answer to the case eight point question. 00:36:39.705 --> 00:36:43.584 Iron deficiency anemia and lead poisoning. 00:36:43.584 --> 00:36:46.545 We might expect to see some basic healing stippling. 00:36:46.712 --> 00:36:53.469 We may not see the severity in the indices that we associated with this case, 00:36:53.719 --> 00:36:57.973 and we also would not see the tendency to have the elliptic sites. 00:36:57.973 --> 00:37:01.310 And in my smaller image here you can see this small oval. 00:37:01.310 --> 00:37:03.562 Each cell that I'm circling okay. 00:37:03.562 --> 00:37:06.857 And we call these in the face of micro hyper chromic 00:37:07.399 --> 00:37:09.526 presentation as pencil cells. 00:37:09.526 --> 00:37:13.322 And they are very you know why I stopped short of saying they're diagnostic 00:37:13.322 --> 00:37:16.659 for iron deficiency anemia in the context of a micro hypo picture. 00:37:16.659 --> 00:37:17.701 Look at this little guy here. 00:37:17.701 --> 00:37:21.205 Micro and not so hypo, but certainly micro. 00:37:21.247 --> 00:37:22.998 We have to think about iron 00:37:23.958 --> 00:37:25.793 pencil cells and iron deficiency. 00:37:25.793 --> 00:37:28.712 So they're very they help complete the picture. 00:37:28.712 --> 00:37:32.424 Anemia of chronic disease is a condition that's associated with patients 00:37:32.424 --> 00:37:36.053 that have some long term inflammation or infection. 00:37:36.053 --> 00:37:36.887 And we were given 00:37:36.887 --> 00:37:41.850 nothing in the clinical presentation to make us think about, anemia. 00:37:41.850 --> 00:37:42.685 Chronic disease. 00:37:42.685 --> 00:37:46.105 Anemia of chronic disease is the most common anemia 00:37:46.105 --> 00:37:49.066 that is associated with hospitalized patients. 00:37:49.149 --> 00:37:53.487 It is related to an imbalance of a master iron regulator called hip Sidon. 00:37:54.321 --> 00:37:57.116 That and the levels of hip Sidon are altered 00:37:57.116 --> 00:38:00.619 when patients have these long term infections and inflammatory conditions. 00:38:01.287 --> 00:38:02.746 And then heterozygous beta one. 00:38:02.746 --> 00:38:08.711 Now, we would expect to see more target cell in this, picture. 00:38:08.711 --> 00:38:13.257 And also again, we were not, given any kind of clinical history 00:38:13.257 --> 00:38:16.635 that would make us think that, the patient had 00:38:18.053 --> 00:38:20.306 a beta thalassemia. 00:38:20.306 --> 00:38:24.893 This particular patient was another graduate of our 00:38:24.893 --> 00:38:28.105 of our medical laboratory science program here at the University of Utah. 00:38:28.397 --> 00:38:32.067 And contacted me, after he knew what was going on. 00:38:32.067 --> 00:38:35.404 He actually has iron deficiency, as we said. 00:38:35.404 --> 00:38:38.490 But when we're talking about iron deficiency anemia in particular, 00:38:38.490 --> 00:38:41.952 it's always important to recognize what is the underlying cause, 00:38:41.952 --> 00:38:46.874 what's etiology, what what has resulted in this condition. 00:38:46.874 --> 00:38:50.961 So so Ida may be the diagnosis, but what really is the underlying problem. 00:38:50.961 --> 00:38:55.257 And as it turns out he has celiac disease and celiac disease. 00:38:55.257 --> 00:38:58.677 Of course people cannot tolerate gliadin 00:38:58.969 --> 00:39:01.972 which is part of our 00:39:02.222 --> 00:39:04.266 in a fraction of the gluten. 00:39:04.266 --> 00:39:09.521 And this results in an imbalance or metabolic problems in the intestine. 00:39:09.772 --> 00:39:13.400 And that can transfer to, not only iron deficiency, 00:39:13.400 --> 00:39:17.654 but sometimes patients have trouble, absorbing folate. 00:39:17.654 --> 00:39:21.325 And B and B12 can also see megalo blast process. 00:39:21.867 --> 00:39:25.996 Processes develop this particular patient our graduate 00:39:25.996 --> 00:39:30.000 as I said, developed iron deficiency as a result of his celiac disease. 00:39:30.000 --> 00:39:34.129 So it's something, disorders to certainly be aware of. 00:39:34.129 --> 00:39:38.550 And from the standpoint of the hematologic findings that are also possible. 00:39:40.386 --> 00:39:43.389 And we have one more case to 00:39:44.098 --> 00:39:47.101 present today. 00:39:47.351 --> 00:39:49.186 Cas9, 00:39:49.186 --> 00:39:52.481 a 33 year old female from Guyana, has experienced 00:39:52.481 --> 00:39:55.484 chronic, low level bone and joint pain all her life. 00:39:56.151 --> 00:40:00.781 At times, she is also so tired and weak she cannot get out of bed in the morning. 00:40:01.490 --> 00:40:04.743 These episodes of extreme weakness can last for several days. 00:40:05.536 --> 00:40:09.206 She visits her physician for a routine evaluation of her condition 00:40:10.541 --> 00:40:13.544 and then her CBC results. 00:40:16.046 --> 00:40:18.048 Again, we can see that, 00:40:18.048 --> 00:40:21.051 the white count is a little elevated. 00:40:21.885 --> 00:40:22.886 Rule of three. 00:40:22.886 --> 00:40:25.389 Pretty close, but she is anemic. 00:40:25.389 --> 00:40:27.891 But the anemia is normal sitting normal chromic. 00:40:27.891 --> 00:40:30.894 As our indices are normal. 00:40:32.354 --> 00:40:35.357 And if you look at, peripheral blood. 00:40:37.109 --> 00:40:40.112 I hope many of you are saying 00:40:41.989 --> 00:40:45.033 We can note here that we have some polychrome Asia, 00:40:45.576 --> 00:40:48.829 a little bit of targeting looks, perhaps a whole jolly body. 00:40:50.456 --> 00:40:53.417 And of course, these cells 00:40:54.251 --> 00:40:57.796 seem to be frequent for you. 00:40:58.422 --> 00:41:00.299 And another 00:41:00.299 --> 00:41:04.344 showing more targeting, and still some that are not quite 00:41:04.344 --> 00:41:07.306 as pronounced as what we just saw. 00:41:08.849 --> 00:41:11.852 So let's open up our next poll. 00:41:14.521 --> 00:41:16.899 Case nine polling question 00:41:16.899 --> 00:41:20.986 what is the most clinically significant RBC abnormality present? 00:41:21.862 --> 00:41:23.572 Elective sites. 00:41:23.572 --> 00:41:24.907 Sickle cells. 00:41:24.907 --> 00:41:27.910 Polychrome Asia target cells. 00:41:29.453 --> 00:41:32.122 So in this case, again I'm not asking for a diagnosis. 00:41:32.122 --> 00:41:35.125 I'm asking for what you think is 00:41:35.876 --> 00:41:38.253 out with some of those morphologic findings. 00:41:38.253 --> 00:41:41.256 I pointed out what's most clinically significant. 00:41:43.258 --> 00:41:44.468 The answer to the case nine 00:41:44.468 --> 00:41:47.471 polling question sickle cells. 00:41:47.846 --> 00:41:51.725 And while, the clipped asides polychrome Asia target cells 00:41:51.725 --> 00:41:56.146 certainly were present, they are not the most clinically significant finding. 00:41:56.355 --> 00:41:59.149 Whenever we see at least one sickle cell event, it's 00:41:59.149 --> 00:42:02.402 going to indicate to us, you know, the potential diagnosis. 00:42:03.946 --> 00:42:04.488 Another 00:42:04.488 --> 00:42:08.784 question to consider with this particular case is the relationship 00:42:08.784 --> 00:42:10.869 between the abnormally shaped red cells 00:42:10.869 --> 00:42:13.872 or with recites and the patient's clinical symptoms. 00:42:13.872 --> 00:42:17.167 Because the sickle cells are abnormally shaped, 00:42:17.376 --> 00:42:20.379 they actually do get stuck in small vessels. 00:42:20.796 --> 00:42:24.633 And this can cause debilitating pain for patients, 00:42:24.800 --> 00:42:29.555 as these cells do not allow oxygen to nourish subsequent tissues. 00:42:30.556 --> 00:42:33.559 This is from a different patient, but I want to point out 00:42:33.559 --> 00:42:37.396 a few features of the sickle cells and this condition. 00:42:37.396 --> 00:42:41.275 So yes, we can see inclusions alcohol, jolly bodies 00:42:41.275 --> 00:42:44.444 here, some poorly cremation this particular patient some targeting. 00:42:44.736 --> 00:42:49.866 But these morphologic features can be seen in other conditions as well 00:42:49.992 --> 00:42:53.996 and have to be put together with clinical findings and other laboratory results 00:42:54.204 --> 00:42:56.331 if and when we see sickle cells. 00:42:56.331 --> 00:42:58.166 Okay, with a classically pointed. 00:42:58.166 --> 00:43:00.168 And that is very significant. 00:43:00.168 --> 00:43:01.962 Here's a nice one over here. 00:43:01.962 --> 00:43:06.300 Now the sickle cells I want to point out will only be seen 00:43:06.592 --> 00:43:10.137 okay when there is 60 over 60% actually 00:43:10.137 --> 00:43:14.016 hemoglobin S present in the patient's cells. 00:43:14.016 --> 00:43:17.436 So someone that has a heterozygous condition of hemoglobin 00:43:17.436 --> 00:43:20.522 S will not have sickle cells present. 00:43:20.772 --> 00:43:23.275 I want to point out a couple things now. 00:43:23.275 --> 00:43:25.152 And you'd seen these on the previous image. 00:43:25.152 --> 00:43:28.614 But sometimes we have cells that are not exactly. 00:43:28.614 --> 00:43:30.282 And this is a good example over here. 00:43:30.282 --> 00:43:33.285 Although sickle cells tend not to have any or central pallor. 00:43:33.577 --> 00:43:37.456 But the sickle cells may be irreversibly sickle cells. 00:43:37.623 --> 00:43:42.002 When these sickle cells circulate to an area where the oxygen tension is 00:43:42.002 --> 00:43:47.090 elevated, then they will go back to the normal disk site, as in this case, 00:43:47.090 --> 00:43:50.719 when they circulate again to where areas of oxygen tension are low. 00:43:50.886 --> 00:43:55.098 Then they sickle and the cells go back and forth and back and forth, and eventually 00:43:55.307 --> 00:43:59.102 they kind of Peter out in their membrane and they can no longer maintain 00:43:59.102 --> 00:44:03.106 their disk shape, and they become irreversibly sickle cells. 00:44:03.231 --> 00:44:06.902 But when they're in between, sometimes they don't look classically sickle. 00:44:07.027 --> 00:44:10.072 And so it's very important to know about that and to recognize it, 00:44:10.364 --> 00:44:11.615 because this laboratory 00:44:11.615 --> 00:44:14.660 is making a diagnosis of sickle cell can be very important. 00:44:15.410 --> 00:44:18.789 I also want to comment about the elevated white count that we saw 00:44:18.789 --> 00:44:19.956 in this particular patient. 00:44:21.041 --> 00:44:21.625 There can 00:44:21.625 --> 00:44:25.504 be a shift from what we call marginal leukocytes 00:44:25.504 --> 00:44:31.301 to the, circulating leukocytes in cases of sickle cell. 00:44:31.301 --> 00:44:34.763 It's not completely understood why these cells break loose from the margins 00:44:34.971 --> 00:44:38.850 of the vessels and circulate, but that can account for some of the increases 00:44:38.850 --> 00:44:42.979 in the in white cells that we see in someone with sickle cell anemia. 00:44:44.690 --> 00:44:47.067 So I want to conclude 00:44:47.067 --> 00:44:50.070 this afternoon session. 00:44:50.445 --> 00:44:53.573 And I'd like you to we're not I'm not going to, 00:44:54.533 --> 00:44:57.869 ask you to, to state this at all, but I just challenge you 00:44:57.869 --> 00:45:00.706 to think of one bit of information or something 00:45:00.706 --> 00:45:04.334 that was new to you today, or something that you had forgotten about 00:45:04.584 --> 00:45:07.546 and were reminded about in today's presentation. 00:45:07.921 --> 00:45:10.882 Something that you can have is your take home message. 00:45:10.882 --> 00:45:16.555 When you go back to your, your routine and your regular jobs, later this afternoon. 00:45:16.763 --> 00:45:21.226 So someone, would ask you, what did you learn today when you attended the webinar? 00:45:21.226 --> 00:45:23.895 I hope there's something that you can readily, 00:45:24.980 --> 00:45:25.522 say.