WEBVTT 00:00:07.966 --> 00:00:10.927 I'm Archana Agarwal, 00:00:10.927 --> 00:00:14.097 I'm assistant professor in the Department of Pathology, 00:00:14.347 --> 00:00:18.977 and also directed the Red Blood Cell laboratory at the Arup Laboratories. 00:00:20.228 --> 00:00:22.522 And today I'm going to talk about 00:00:22.522 --> 00:00:25.525 the diagnostic approach to anemia. 00:00:26.317 --> 00:00:29.320 In the outline of the talk is, 00:00:30.155 --> 00:00:33.783 I'll talk about the basic hematological parameters 00:00:33.783 --> 00:00:38.496 and go over some of the parameters which we use commonly 00:00:38.955 --> 00:00:41.583 in the diagnosis of anemia. 00:00:41.583 --> 00:00:44.586 We'll also talk about the different types of anemia 00:00:45.045 --> 00:00:47.714 and their clinical manifestations. 00:00:47.714 --> 00:00:51.968 And then focus on the relevant diagnostic tests 00:00:52.302 --> 00:00:55.305 for different types of anemia. 00:00:56.681 --> 00:00:58.850 The basic hematological laboratory 00:00:58.850 --> 00:01:03.104 test is which we use for the day to day 00:01:03.104 --> 00:01:07.317 diagnosis of anemia is the complete blood count. 00:01:07.317 --> 00:01:09.861 And we all are aware of complete blood count. 00:01:09.861 --> 00:01:13.782 But some of the parameters in the CBC can be confusing. 00:01:13.782 --> 00:01:18.953 And we'll I'll talk a little bit more about those parameters in detail in my 00:01:18.995 --> 00:01:20.246 next couple of slides. 00:01:21.456 --> 00:01:26.127 CBC includes mostly the amount of hemoglobin. 00:01:26.127 --> 00:01:30.173 It also talks about the characteristics of the red blood, says 00:01:30.173 --> 00:01:34.135 the number of red blood cells size, and the shapes of the red blood cells. 00:01:34.469 --> 00:01:38.890 It also gives us information about the white blood cells and platelets, 00:01:40.225 --> 00:01:42.519 white blood cells, the, the number 00:01:42.519 --> 00:01:47.607 and the and information about the platelets help us in broad 00:01:47.607 --> 00:01:51.194 differential diagnosis of anemia because there are. 00:01:53.196 --> 00:01:54.989 Different, 00:01:54.989 --> 00:01:57.992 types of anemia, which can also 00:01:58.159 --> 00:02:02.080 have, can have impact on the white blood cells and platelets. 00:02:02.080 --> 00:02:05.083 And we'll go over some of those later in our, 00:02:05.583 --> 00:02:08.169 presentation. 00:02:08.169 --> 00:02:09.504 We look at some 00:02:09.504 --> 00:02:13.299 sometime we have to look at the visual smear manually 00:02:13.299 --> 00:02:16.553 when some of the parameters of the CBC goes 00:02:16.553 --> 00:02:19.556 beyond the established parameters, 00:02:19.597 --> 00:02:23.476 like if we see some atypical or the, the, the instrument 00:02:23.476 --> 00:02:27.480 flags, some of the parameters instrument is not enabled. 00:02:27.647 --> 00:02:30.608 It's not able to diagnose some of the, identify 00:02:30.608 --> 00:02:33.862 some of the cells or it's like completely confused. 00:02:33.862 --> 00:02:39.492 So we need to look at the peripheral smear and make other interpretation manually. 00:02:39.492 --> 00:02:44.247 Like if it's if there is, atypical lymphocytes or if there is a blast, 00:02:44.539 --> 00:02:47.750 then we need to look at it and come up with a manual differential. 00:02:49.878 --> 00:02:54.048 So talking a little bit more about the CBC or complete blood count, 00:02:54.048 --> 00:02:58.511 which is one of the most important parameters in the diagnosis of anemia. 00:03:01.306 --> 00:03:03.099 These are the most common 00:03:03.099 --> 00:03:06.561 parameter which we see on a day to day basis. 00:03:06.561 --> 00:03:08.563 When we are looking at the CBC. 00:03:08.563 --> 00:03:10.440 There are some other parameters, 00:03:10.440 --> 00:03:14.110 but but most of the time we don't really use like platelet volume. 00:03:14.360 --> 00:03:17.363 You'll see that, all the time in the CBC. 00:03:17.363 --> 00:03:20.867 But for all practical purposes, 99.9% of the time 00:03:20.867 --> 00:03:24.787 we don't usually use those parameters in our diagnostic workup. 00:03:25.246 --> 00:03:27.790 These are the most common parameters which are used 00:03:27.790 --> 00:03:30.793 hemoglobin, hematocrit and red blood cell count. 00:03:31.002 --> 00:03:35.715 The first three gives us idea about the anemia. 00:03:35.715 --> 00:03:39.677 How what is the the the amount of anemia. 00:03:39.677 --> 00:03:40.803 The quantity of anemia. 00:03:40.803 --> 00:03:44.933 It's, if it's a mild anemia, moderate anemia or severe anemia. 00:03:45.183 --> 00:03:49.520 So we can come up with that based upon the red blood cell count, hematocrit 00:03:49.520 --> 00:03:53.691 and the hemoglobin MCV, MC, and mCAT. 00:03:53.691 --> 00:03:58.321 See, so McVie basically tells us about the size of the red blood cell. 00:03:58.571 --> 00:04:00.782 Is the mean cell volume. 00:04:00.782 --> 00:04:04.244 And this is one of the most important 00:04:04.244 --> 00:04:08.248 parameters in our diagnostic workup of anemia. 00:04:08.498 --> 00:04:13.544 Whether it's a microscopic anemia or a macro Citic anemia or a normal Citic anemia. 00:04:14.587 --> 00:04:16.422 MC, H and MC. 00:04:16.422 --> 00:04:20.718 Actually, these two parameters also included all the time in the CBC. 00:04:21.344 --> 00:04:26.140 It's not that useful for our diagnostic workup. 00:04:26.432 --> 00:04:32.397 Most of the time NC H and NC it c goes along with Ncbi only rarely. 00:04:32.397 --> 00:04:35.650 In some of the red anemia is the mCAT. 00:04:35.650 --> 00:04:36.442 C or NC. 00:04:36.442 --> 00:04:41.114 H would be different from Ncbi and we'll talk about that later in our, 00:04:42.490 --> 00:04:43.825 presentation. 00:04:43.825 --> 00:04:48.538 Red RW or red cell distribution with it. 00:04:48.705 --> 00:04:54.961 It gives us idea about the range of the red blood cell size. 00:04:55.211 --> 00:04:58.172 So the if it's normal, the percentage of red blood 00:04:58.172 --> 00:05:02.010 cell is in the normal or is in the normal range. 00:05:02.302 --> 00:05:06.347 That means pretty much all the red blood cells are of the similar size. 00:05:06.764 --> 00:05:09.809 If it's like really high, that tells us 00:05:10.059 --> 00:05:13.604 that some of the red blood cells are smaller in size, some of them are, 00:05:14.856 --> 00:05:17.650 really larger in size, and some of them are normal. 00:05:17.650 --> 00:05:20.320 And RTW does help us in 00:05:20.320 --> 00:05:24.782 some of the diagnostic workup or differential diagnosis of anemia. 00:05:24.782 --> 00:05:27.577 And we will discuss that again, 00:05:27.577 --> 00:05:31.456 as I discussed earlier, white blood cell and platelet count. 00:05:32.373 --> 00:05:34.834 Although it's not directly related 00:05:34.834 --> 00:05:38.588 to the diagnostic work of of anemia, but there are some 00:05:39.630 --> 00:05:41.716 it helps us in the differential diagnosis 00:05:41.716 --> 00:05:44.719 of anemia. 00:05:45.636 --> 00:05:46.971 Again, elaborating a little bit 00:05:46.971 --> 00:05:51.100 more on the red blood cell parameters, how these are measured. 00:05:51.434 --> 00:05:56.314 Hemoglobin is measured directly as the absorbance of hemoglobin. 00:05:57.065 --> 00:06:00.234 And most of these parameters hemoglobin RBC count. 00:06:00.234 --> 00:06:03.863 These are measured directly by the instruments. 00:06:04.155 --> 00:06:08.868 And flow cytometry is one of the common method, to get these parameters, 00:06:09.327 --> 00:06:13.373 red blood cell count gives us the direct it measure directly by the impedance. 00:06:14.332 --> 00:06:15.833 Hematocrit means 00:06:15.833 --> 00:06:21.339 basically it's the ratio of that blood cell to the volume of whole blood. 00:06:21.339 --> 00:06:24.217 And it's a calculated most of the time is to calculate it. 00:06:24.217 --> 00:06:27.512 But some of the newer instrument also gives us the hematocrit directly. 00:06:28.679 --> 00:06:32.100 MCV is the mean height of the voltage. 00:06:32.100 --> 00:06:35.103 So MCV is basically it's 00:06:35.478 --> 00:06:39.315 as determined by the histogram of the red blood cell size. 00:06:39.565 --> 00:06:44.487 And it's it's actually the mean of the red blood cell size. 00:06:44.487 --> 00:06:49.659 And that cell distribution weight, which is not included here is is the 00:06:50.284 --> 00:06:54.872 coefficient of variation of the mean, or size of the red blood cells. 00:06:55.665 --> 00:06:58.501 Mickey and Mickey. 00:06:58.501 --> 00:07:02.463 Although it's given directly by the newer instrument, it can also 00:07:02.463 --> 00:07:06.676 be calculated based upon the right blood cell number and the hematocrit. 00:07:07.093 --> 00:07:12.140 As I as I said earlier, also, Mickey and Mickey most of the time tag 00:07:12.140 --> 00:07:17.353 along with the parameters tag along with the Ncbi and it's not really useful. 00:07:17.353 --> 00:07:21.899 A whole lot in like individually if you're looking at MSI and Mickey, 00:07:21.983 --> 00:07:25.820 see only rarely the use like Mickey 00:07:25.820 --> 00:07:30.074 or see it as like, individual parameter for the diagnostic workup. 00:07:32.952 --> 00:07:34.537 Definition of anemia. 00:07:34.537 --> 00:07:39.208 So anemia comes from the Greek word and it means without blood. 00:07:40.626 --> 00:07:42.879 It's it's some manifestation. 00:07:42.879 --> 00:07:47.258 It's not a disease of numerous causes. 00:07:47.258 --> 00:07:52.472 And they're like I mean they're like more than 20 different causes of anemia. 00:07:53.097 --> 00:07:57.643 It's it's basically a physiological manifestation of a disease, 00:07:57.643 --> 00:07:59.937 underlying disease. 00:07:59.937 --> 00:08:03.191 It's it's the condition, their capacity of the blood 00:08:03.191 --> 00:08:08.321 to transport oxygen to tissues is reduced because of the underlying condition. 00:08:08.654 --> 00:08:13.117 And it's defined by decreased hemoglobin, RBC count and hematocrit 00:08:13.326 --> 00:08:16.537 and all these three parameters, which are the first three. 00:08:16.537 --> 00:08:19.665 Most of the time, the first three parameters in the CBC, 00:08:20.833 --> 00:08:25.296 we use all these three parameters in our definition of anemia. 00:08:25.296 --> 00:08:29.967 Sometimes you'll see that, only RBC count is decreased. 00:08:30.927 --> 00:08:35.556 Sometimes hematocrit only might be decreased like as an individual parameter. 00:08:36.057 --> 00:08:40.520 And it's like if it's one of these three parameters are decreased. 00:08:40.520 --> 00:08:43.523 We would just call it like a borderline anemia. 00:08:43.606 --> 00:08:47.068 If we need at least for our practical purposes, 00:08:47.068 --> 00:08:51.280 we need at least two different parameters to go down to call it anemia. 00:08:51.447 --> 00:08:53.950 If it's like only one decrease in hemoglobin, 00:08:53.950 --> 00:08:56.536 then we'll just call it maybe borderline anemia. 00:08:56.536 --> 00:08:58.329 We need at least two different parameters. 00:08:59.497 --> 00:08:59.997 In most 00:08:59.997 --> 00:09:03.042 of the time, if it's like a clear cut case of anemia, 00:09:03.042 --> 00:09:07.004 all these three parameters would be like out of range 00:09:08.339 --> 00:09:13.177 treatment or the anemia depends on discovering the underlying cause. 00:09:13.177 --> 00:09:19.100 That's the most important, way of treat anemia to, to basically determine 00:09:19.100 --> 00:09:22.103 what's the underlying cause and then treat that. 00:09:25.856 --> 00:09:28.859 So evaluating anemia in the lab 00:09:28.985 --> 00:09:31.988 we need basic information size of the red blood cells. 00:09:32.655 --> 00:09:34.699 Whether it's small, normal or big. 00:09:34.699 --> 00:09:38.077 And that's determined by MCV mean cell volume. 00:09:39.036 --> 00:09:43.332 We need to look at the microscope see if there are any atypical cells 00:09:43.666 --> 00:09:46.669 like sickle cell is one of the common 00:09:47.712 --> 00:09:50.923 example, if we are seeing sickle cells, that means the patient has sickle 00:09:50.923 --> 00:09:52.508 cell anemia. 00:09:52.508 --> 00:09:55.511 Also, we need to look at the platelets and the leukocytes 00:09:55.511 --> 00:09:58.514 because as I mentioned earlier, there are a lot of different, 00:09:58.681 --> 00:10:02.268 causes of anemia that not only includes red blood cells, 00:10:02.268 --> 00:10:05.479 but also includes white blood cells and platelets. 00:10:05.771 --> 00:10:09.400 And that basically leads to pan cytokine, not only anemia, 00:10:09.400 --> 00:10:13.029 but cytokine means decrease in all three parameters 00:10:13.362 --> 00:10:17.158 anemia, as well as decrease in leukocytes and platelets. 00:10:18.326 --> 00:10:22.413 That site count is it gives us idea 00:10:22.413 --> 00:10:27.752 about the ability of the bone marrow to respond to anemia. 00:10:27.752 --> 00:10:32.214 And this is again we'll talk we'll discuss that in little bit more detail 00:10:32.214 --> 00:10:35.217 when we'll talk about the causes of normal septic anemia. 00:10:35.676 --> 00:10:40.681 As this becomes really important to know how the bone marrow is functioning. 00:10:40.931 --> 00:10:44.894 If the bone marrow is involved in certain diseases, like there's 00:10:44.894 --> 00:10:48.731 a cancer involving the bone marrow, or if some disease like, 00:10:50.066 --> 00:10:53.069 myelodysplastic syndrome or some other, 00:10:53.653 --> 00:10:56.864 leukemia or something which is involved in the bone marrow, then 00:10:56.864 --> 00:11:02.328 one bone marrow would not be functioning to recover or respond to the anemia. 00:11:02.828 --> 00:11:08.167 So that gives us an idea about the bone marrow, its capacity to respond to anemia. 00:11:08.167 --> 00:11:09.251 The reticular site count. 00:11:09.251 --> 00:11:12.672 So ridiculous type is basically a precursor of red blood cells. 00:11:13.881 --> 00:11:15.174 So reticular 00:11:15.174 --> 00:11:19.595 side count and it's it's in the red in the peripheral blood circulation. 00:11:19.595 --> 00:11:21.889 It remains only for like 24 hours. 00:11:21.889 --> 00:11:24.934 And then it develops into a mature red blood cell. 00:11:25.267 --> 00:11:29.063 So if it's if the number of reticular strike is really high 00:11:29.063 --> 00:11:30.606 in the peripheral circulation, 00:11:30.606 --> 00:11:34.026 it means that the bone marrow is really functioning 00:11:34.151 --> 00:11:38.614 to respond to the anemia and turning out a lot of these immature 00:11:38.614 --> 00:11:41.242 red blood cells into the peripheral circulation. 00:11:41.242 --> 00:11:44.286 So that really helps us in basically 00:11:44.286 --> 00:11:47.415 defining whether the bone marrow is functioning or not. 00:11:47.707 --> 00:11:50.710 And that that is really important for our 00:11:50.918 --> 00:11:55.631 not only for our diagnostic purposes, but also for the treatment purposes. 00:11:56.257 --> 00:11:58.759 Later on, if the bone marrow is not functioning, 00:11:58.759 --> 00:12:01.762 then it becomes very difficult for a treating physician 00:12:01.846 --> 00:12:05.224 to treat that anemia, because that might 00:12:05.224 --> 00:12:10.604 that might need the treatment, to get rid of either leukemia 00:12:10.604 --> 00:12:14.859 or cancer from the bone marrow or bone marrow transplant, things like that. 00:12:14.859 --> 00:12:18.279 But if the bone marrow is functioning, fine, then if we treat 00:12:18.279 --> 00:12:21.449 the peripheral cause of anemia and the patients should be fine. 00:12:21.615 --> 00:12:25.786 So ridiculous, I count is one of the really important parameter 00:12:26.871 --> 00:12:28.748 in basically, 00:12:28.748 --> 00:12:31.083 determining the cause of anemia. 00:12:31.083 --> 00:12:35.504 And then there are a lot of other, evidence of destruction of red blood cells 00:12:36.464 --> 00:12:40.885 like elevated lactic dehydrogenase and the bilirubin, 00:12:40.885 --> 00:12:44.388 which is the breakdown product of red blood cell. 00:12:44.805 --> 00:12:47.641 So these basically gives us an idea 00:12:47.641 --> 00:12:50.686 about what's going on with the red blood cells. 00:12:50.936 --> 00:12:54.607 If if the red blood cells are getting destroyed, which is like 00:12:54.607 --> 00:12:56.233 which is the hemolytic anemia. 00:12:56.233 --> 00:12:59.528 And that's one of the most common cause for normal Citic anemia. 00:12:59.528 --> 00:13:01.614 We'll talk about that again. 00:13:01.614 --> 00:13:03.657 In our later, discussion. 00:13:03.657 --> 00:13:07.244 So these are the common parameters we need to start 00:13:07.244 --> 00:13:10.664 when we are basically working up our anemia. 00:13:10.915 --> 00:13:12.708 What's the size of the red blood cells? 00:13:12.708 --> 00:13:14.960 What does it look like under the microscope? 00:13:14.960 --> 00:13:17.797 What's the other, parameters doing? 00:13:17.797 --> 00:13:19.423 How the bone marrow is functioning. 00:13:19.423 --> 00:13:23.385 And if the, if there is a peripheral destruction of the red blood cell. 00:13:25.888 --> 00:13:29.308 So a practical approach where we start the first 00:13:29.308 --> 00:13:33.437 and the most important thing is to know the size of the red blood cell. 00:13:33.813 --> 00:13:38.859 And we cannot really I mean, we can try to look at under the microscope 00:13:38.859 --> 00:13:42.863 and try to guess, like, estimate the size of the red blood cell. 00:13:43.155 --> 00:13:46.116 So most of the time, what happens, 00:13:46.325 --> 00:13:49.161 like, as a human pathologist, the, 00:13:49.161 --> 00:13:53.415 we are trained to basically estimate the size of the red blood cell. 00:13:53.916 --> 00:13:58.170 So it's usually equal, like it should be somewhat 00:13:58.170 --> 00:14:02.091 the size of the nucleus of a neutrophil. 00:14:02.800 --> 00:14:05.886 And if it's smaller than that, then we call it a micro setting. 00:14:05.886 --> 00:14:07.596 But it's just an estimate. 00:14:07.596 --> 00:14:10.599 It's a very, very subjective 00:14:10.724 --> 00:14:11.684 parameter. 00:14:11.684 --> 00:14:18.107 We for all practical purposes, we do not rely on our basically eyes 00:14:18.107 --> 00:14:21.861 or a microscope to determine the size of the red blood cell. 00:14:22.778 --> 00:14:25.781 It can give us some idea, but that's about it. 00:14:26.031 --> 00:14:29.326 We rely on we rely on the instrument. 00:14:29.660 --> 00:14:34.123 The main cell volume or the Ncbi to to know the size of the red blood cell. 00:14:35.541 --> 00:14:37.167 The normal reference range 00:14:37.167 --> 00:14:41.255 and the reference range varies from the laboratory to laboratory. 00:14:41.797 --> 00:14:45.009 And but most of the time it it's like anywhere 00:14:45.009 --> 00:14:48.220 from 80 to 90 8 or 100. 00:14:48.596 --> 00:14:51.807 So the estimate will be around 80 to 100. 00:14:52.391 --> 00:14:57.313 But it can vary anywhere from 78 to 90 5 or 98, something like that. 00:14:58.272 --> 00:15:03.777 Any time the MCV is lower than the reference range 00:15:04.111 --> 00:15:08.157 established by the laboratory, we call it a micro Citic anemia. 00:15:08.157 --> 00:15:12.620 So that means the size of the red blood cell, small and micro means small. 00:15:12.870 --> 00:15:16.540 So that means the size of the red blood cells are smaller. 00:15:17.041 --> 00:15:20.461 And if it's more than 100 we call it a macro Citic anemia. 00:15:20.586 --> 00:15:23.589 That means the red blood cells are much larger in size. 00:15:23.964 --> 00:15:28.719 This is the basic, basic definition of the the anemia diagnosis. 00:15:32.056 --> 00:15:35.017 Based upon the size of the red blood cell. 00:15:35.351 --> 00:15:40.105 So if it's a micro Citic anemia, the most common causes of micro 00:15:40.522 --> 00:15:43.359 or smaller size of the red blood cells 00:15:43.359 --> 00:15:46.362 are these three iron deficiency 00:15:46.362 --> 00:15:49.365 anemia, chronic disease and Palestinians. 00:15:49.573 --> 00:15:52.576 These are also the common 00:15:52.743 --> 00:15:55.996 not so common, although these are the established causes 00:15:55.996 --> 00:15:59.416 of like anemia and hereditary status psychosis. 00:15:59.708 --> 00:16:01.585 We do see that quite often. 00:16:01.585 --> 00:16:03.796 We'll talk about that. 00:16:03.796 --> 00:16:05.673 But, head 00:16:05.673 --> 00:16:09.051 to X-linked syndrome, plastic anemia and lead poisoning. 00:16:09.051 --> 00:16:10.970 These are rare. 00:16:10.970 --> 00:16:14.807 But these all three, six of them come under the common 00:16:14.807 --> 00:16:18.644 differential diagnosis or the differential diagnosis of micro anemia. 00:16:19.311 --> 00:16:22.398 The most common would be iron deficiency anemia. 00:16:22.398 --> 00:16:25.401 And we'll talk about that in a little bit detail. 00:16:25.484 --> 00:16:28.487 Iron deficiency anemia and thalassemia. 00:16:29.113 --> 00:16:33.909 Anemia of chronic disease is also a common cause of anemia. 00:16:34.201 --> 00:16:37.746 But again anemia of chronic disease encompasses 00:16:37.746 --> 00:16:40.624 so many different causes of anemia. 00:16:40.624 --> 00:16:42.584 Underlying like, diseases. 00:16:45.295 --> 00:16:49.299 So it kind of becomes sometimes 00:16:49.299 --> 00:16:52.845 it becomes a little bit difficult to diagnose an image of chronic disease 00:16:53.053 --> 00:16:56.348 because it can also manifest as normal cystic anemia. 00:16:56.682 --> 00:16:59.601 So for practical purposes, if we are seeing a case 00:16:59.601 --> 00:17:02.771 of micro Citic anemia, the most common differential 00:17:02.771 --> 00:17:06.400 which should come to anyone's mind is iron deficiency anemia. 00:17:06.817 --> 00:17:09.862 And thalassemia is two 00:17:10.237 --> 00:17:13.282 especially based upon the ethnicity of the population. 00:17:13.574 --> 00:17:16.702 Thalassemia has also become one of the common differential diagnosis. 00:17:16.827 --> 00:17:19.830 And we'll talk about the ethnicity part later on. 00:17:21.373 --> 00:17:24.043 So the first first thing first, iron deficiency 00:17:24.043 --> 00:17:27.963 anemia is the most common cause of anemia. 00:17:27.963 --> 00:17:30.966 Microsatellite anemia or anemia worldwide. 00:17:31.133 --> 00:17:34.136 It's it's 00:17:34.386 --> 00:17:37.389 most commonly it happens due to bleeding. 00:17:38.140 --> 00:17:41.226 But, it can also happen in some of the, 00:17:42.853 --> 00:17:44.438 underdeveloped countries. 00:17:44.438 --> 00:17:47.941 It happens due to nutritional deficiency and is also the commonest 00:17:47.941 --> 00:17:51.153 cause of anemia worldwide because of the nutritional deficiency. 00:17:51.487 --> 00:17:54.573 But in the United States, most of the time 00:17:54.573 --> 00:17:58.035 it's due to bleeding, mostly in the elderly population. 00:17:58.452 --> 00:18:03.373 Either is GI, gastrointestinal bleeding or bleeding due to some other cause, 00:18:03.373 --> 00:18:08.420 or cancer related colon cancer is one of the common cause leading to bleeding. 00:18:09.505 --> 00:18:11.048 Colon cancer causing bleeding 00:18:11.048 --> 00:18:15.260 and then developing into iron deficiency anemia again in females. 00:18:15.260 --> 00:18:17.137 Because of the menstrual cycle, bleeding 00:18:17.137 --> 00:18:20.557 is, bleeding can lead to anemia all the time. 00:18:22.392 --> 00:18:23.977 Females 00:18:23.977 --> 00:18:27.272 having cervical cancer or endometrial cancer. 00:18:27.272 --> 00:18:30.275 These can also lead to bleeding and cause extensive anemia. 00:18:30.526 --> 00:18:33.612 So any cause bleeding in the United States is the most common 00:18:33.612 --> 00:18:36.615 cause of iron deficiency anemia. 00:18:36.698 --> 00:18:37.116 Iron. 00:18:37.116 --> 00:18:39.451 Some of the iron, in fact 00:18:39.451 --> 00:18:42.704 body iron, 80% of the functional 00:18:42.704 --> 00:18:46.500 iron is seen in the form of hemoglobin myoglobin, 00:18:46.500 --> 00:18:50.712 which is in the muscle and cytochrome c, which is commonly seen in the. 00:18:50.712 --> 00:18:52.673 Some of the enzymes. 00:18:52.673 --> 00:18:55.259 About 20% of the iron is seen 00:18:55.259 --> 00:18:59.680 in the storage form, so 80% of the functional 00:18:59.680 --> 00:19:03.725 iron, is basically gets circulated on a daily basis. 00:19:03.725 --> 00:19:08.105 And then about 20% it's which is in the storage form, 00:19:08.438 --> 00:19:13.110 it's only used when there is iron deficiency or a sudden 00:19:13.735 --> 00:19:17.865 need of more iron because of the severe bleeding or, 00:19:19.366 --> 00:19:22.202 like sudden like, 00:19:22.202 --> 00:19:24.163 some other reason we, 00:19:24.163 --> 00:19:27.875 called, which leads to bleeding and cause, severe 00:19:27.875 --> 00:19:30.878 iron deficiency anemia, like accident or something. 00:19:32.421 --> 00:19:33.964 Iron. 00:19:33.964 --> 00:19:36.300 It's absorbed in the small intestine. 00:19:36.300 --> 00:19:39.178 Duodenum is the most, 90% of 00:19:39.178 --> 00:19:42.181 the iron would be absorbed from the duodenum. 00:19:43.140 --> 00:19:46.435 Transferrin is the transporter 00:19:46.435 --> 00:19:50.731 iron transporter in the peripheral blood in which 00:19:50.772 --> 00:19:54.943 40 of the iron in the circulation would be bound to transferrin. 00:19:55.360 --> 00:20:01.450 So transferrin saturation in a normal iron, if the patient is not iron 00:20:01.450 --> 00:20:06.622 deprived, has a normal percentage of iron in the peripheral blood circulation 00:20:06.955 --> 00:20:09.958 it would be transferring, would bind to the iron. 00:20:11.543 --> 00:20:15.589 Felting is the storage form of iron which is seen inside the bone 00:20:15.589 --> 00:20:19.760 marrow or, macrophages, spleen or liver. 00:20:19.760 --> 00:20:22.804 So any places where iron is stored, 00:20:23.639 --> 00:20:26.600 it's stored in the form of sedative hemo. 00:20:26.600 --> 00:20:30.938 It is derived from the fat in and it's the long term storage of that. 00:20:30.938 --> 00:20:33.941 And it's seen most commonly in the, 00:20:34.274 --> 00:20:36.568 kidney, renal tubules. 00:20:38.153 --> 00:20:40.572 So if we are trying to 00:20:40.572 --> 00:20:44.409 establish a diagnosis of iron deficiency anemia, 00:20:44.743 --> 00:20:47.746 the common parameters would be 00:20:48.580 --> 00:20:51.041 serum iron. 00:20:51.041 --> 00:20:52.876 So I didn't studies. 00:20:52.876 --> 00:20:55.545 Low serum iron basically 00:20:55.545 --> 00:20:58.548 defines iron deficiency anemia. 00:20:59.007 --> 00:21:02.010 But low serum iron, 00:21:02.135 --> 00:21:05.555 can also be seen in anemia, chronic disorder, 00:21:05.847 --> 00:21:08.558 which is also one of the commonest, 00:21:08.558 --> 00:21:11.144 cause of micro anemia. 00:21:11.144 --> 00:21:13.105 So if we see, 00:21:13.105 --> 00:21:16.566 a patient or on a, a patient with iron, 00:21:17.359 --> 00:21:21.196 low serum iron, the the most common differential which should come to anyone's 00:21:21.196 --> 00:21:25.325 mind is iron deficiency anemia and anemia of chronic disorder. 00:21:26.702 --> 00:21:29.955 However, based on some other parameter, we can, 00:21:30.831 --> 00:21:33.166 narrow down our differential 00:21:33.166 --> 00:21:35.794 in iron deficiency anemia. 00:21:35.794 --> 00:21:39.131 All pretty much all the cases of iron deficiency 00:21:39.131 --> 00:21:43.218 anemia should have low 13, which is the storage form of iron 00:21:43.427 --> 00:21:46.430 and one of the most important parameter 00:21:46.555 --> 00:21:49.558 to diagnose iron deficiency anemia. 00:21:49.766 --> 00:21:52.811 So 13 as I described in 00:21:52.811 --> 00:21:55.981 the previous slide, is the storage form of iron. 00:21:57.316 --> 00:22:00.319 So if there is an iron deficiency anemia, 00:22:01.737 --> 00:22:04.740 if storage form of iron also goes down 00:22:04.906 --> 00:22:10.662 so low, if, if a patient has a low serum iron and low ferritin, 00:22:10.662 --> 00:22:13.665 that means the patient has identified anemia 00:22:13.832 --> 00:22:17.961 in anemia of chronic disorder, we can see low serum iron. 00:22:17.961 --> 00:22:21.798 But pretty much all of the iron, even though set of iron is low in that 00:22:22.090 --> 00:22:25.635 in those patients the storage form of iron 00:22:25.635 --> 00:22:28.930 is usually either normal or in the high range. 00:22:29.222 --> 00:22:33.310 So if we see high fat I'm sorry, ferritin 00:22:33.852 --> 00:22:37.022 or normal ferritin, it could be 00:22:38.190 --> 00:22:42.986 anemia of chronic disorder but low it in for all practical purposes 00:22:43.945 --> 00:22:46.948 is diagnostic of iron deficiency anemia. 00:22:47.574 --> 00:22:49.659 High total serum iron 00:22:49.659 --> 00:22:52.704 binding capacity, also known as IBC. It. 00:22:52.871 --> 00:22:55.874 It basically gives us an idea about the transferrin 00:22:55.874 --> 00:22:59.086 saturation or transferrin concentration. 00:22:59.294 --> 00:23:02.297 So if there is a low serum iron, 00:23:02.547 --> 00:23:06.301 the binding capacity of the transferrin is much higher. 00:23:06.551 --> 00:23:09.554 So in cases of iron deficiency anemia, the iron 00:23:09.596 --> 00:23:12.599 binding capacity of the transferrin is much higher. 00:23:12.849 --> 00:23:18.897 So in combination of all these parameters, it's usually possible 00:23:18.897 --> 00:23:23.026 to distinguish between iron deficiency anemia and thalassemia. 00:23:24.611 --> 00:23:27.614 Sorry, anemia of chronic disorder. 00:23:28.073 --> 00:23:32.035 Most of the time 95 or 9798% of the time. 00:23:32.494 --> 00:23:35.622 All these serum markers would be helpful. 00:23:35.956 --> 00:23:38.708 Once in a while it becomes, 00:23:38.708 --> 00:23:42.879 important, or it's required to do a bone marrow. 00:23:42.879 --> 00:23:46.091 It's an invasive procedure, invasive invasive procedure. 00:23:46.425 --> 00:23:50.762 It it needs local anesthetic and also is a painful procedure. 00:23:50.762 --> 00:23:55.517 So most of the time physicians would try to avoid doing a bone marrow 00:23:55.517 --> 00:24:00.188 just for the diagnosis of iron deficiency anemia, unless they all 00:24:00.188 --> 00:24:04.568 these parameters are failed or there are conditions that there could 00:24:04.568 --> 00:24:09.364 be an overlap of iron deficiency anemia and an email chronic disorder. 00:24:09.364 --> 00:24:14.202 So a patient could have like, a chronic disease like rheumatoid 00:24:14.202 --> 00:24:17.330 arthritis and could also have iron deficiency anemia. 00:24:17.497 --> 00:24:19.082 So in those patients there 00:24:19.082 --> 00:24:23.128 there are two or different other factors compounding a diagnosis. 00:24:23.378 --> 00:24:26.506 It becomes once in a while it's 00:24:26.506 --> 00:24:29.885 necessary to do a bone marrow to determine the cause. 00:24:30.302 --> 00:24:34.931 And for in the bone marrow, in iron deficiency anemia, 00:24:36.099 --> 00:24:38.852 the bone marrow stories, iron should be decreased. 00:24:38.852 --> 00:24:44.524 So bone marrow stores iron decreased bone marrow stories iron is the gold 00:24:44.524 --> 00:24:47.652 standard for the diagnosis of iron deficiency anemia. 00:24:47.861 --> 00:24:51.490 That's basically if there is a decrease in bone marrow status, iron 00:24:51.490 --> 00:24:55.243 that's diagnostic of foreign deficiency anemia in all the other 00:24:55.660 --> 00:24:58.497 differential diagnosis like thalassemia 00:24:58.497 --> 00:25:03.793 or an email of chronic disorders either bone marrow iron is normal or increase. 00:25:03.793 --> 00:25:07.255 So that's like one of the gold standard for that since the anemia. 00:25:07.589 --> 00:25:11.384 But most of the time it's not 95 or 97% of the time 00:25:11.384 --> 00:25:14.471 it's not really required to develop bone marrow. 00:25:14.930 --> 00:25:19.184 The other set of markers would be helpful to distinguish between those, 00:25:20.560 --> 00:25:23.563 differential diagnosis. 00:25:25.273 --> 00:25:28.276 So one of the other common 00:25:28.276 --> 00:25:31.321 differential for micro static anemia is thalassemia 00:25:33.198 --> 00:25:34.866 in in 00:25:34.866 --> 00:25:40.288 United States in the last 5 or 10 years, because of the migration, it's becoming 00:25:40.288 --> 00:25:44.125 quite common to see cases of thalassemia, 00:25:44.709 --> 00:25:48.672 especially in, like recent immigrant. 00:25:49.464 --> 00:25:51.967 It's Southeast Asian, 00:25:51.967 --> 00:25:54.469 population, Mediterranean population. 00:25:54.469 --> 00:25:57.180 So thalassemia, as are commonly seen in 00:25:57.180 --> 00:26:00.559 certain ethnic populations, it's becoming more and more common. 00:26:01.059 --> 00:26:04.896 And we should always remember to keep that in our differential. 00:26:04.896 --> 00:26:08.316 If we are seeing a case of microscopic hypertrophic anemia 00:26:09.067 --> 00:26:11.945 and people fail to realize that, 00:26:11.945 --> 00:26:15.699 because we always think that Latinas are not common in United States, 00:26:15.699 --> 00:26:20.620 but we see we are seeing a lot of cases with thalassemia, especially in migrant 00:26:20.662 --> 00:26:22.247 recently migrant population. 00:26:22.247 --> 00:26:25.333 So it should always we should always remember that 00:26:25.750 --> 00:26:29.170 like Pacific hypo chromic chromic anemia is not only caused by 00:26:29.379 --> 00:26:33.466 iron deficiency anemia or an email chronic disorder thalassemia 00:26:33.466 --> 00:26:37.304 that becoming really, really common in this part of the world too. 00:26:38.388 --> 00:26:40.390 So what is thalassemia? 00:26:40.390 --> 00:26:43.393 Hemoglobin, as we might remember, is a tension 00:26:43.685 --> 00:26:47.647 with two alpha globin, two alpha chains, and two beta chains. 00:26:48.315 --> 00:26:52.319 So thalassemia happen when there is imbalance 00:26:52.319 --> 00:26:55.322 between these alpha and beta chains. 00:26:56.531 --> 00:26:59.075 So there are two different kinds of thalassemia 00:26:59.075 --> 00:27:02.078 alpha and beta thalassemia. 00:27:02.120 --> 00:27:06.541 And based upon the production of alpha chains or beta chains. 00:27:06.541 --> 00:27:11.379 Because both these chains are required, it's a type trauma to form hemoglobin. 00:27:11.713 --> 00:27:15.634 So if there is a decrease in let's see alpha chain, 00:27:16.134 --> 00:27:20.138 then the beta chains is in relative axis. 00:27:20.138 --> 00:27:23.266 And it doesn't have enough alpha chain to bind to. 00:27:23.266 --> 00:27:26.102 So always alpha bind to beta. 00:27:26.102 --> 00:27:29.105 And if there is free 00:27:29.564 --> 00:27:32.776 beta they don't have anything to bind to. 00:27:32.859 --> 00:27:35.904 The free circulating beta or free circulating 00:27:35.904 --> 00:27:39.366 alpha is much more toxic to the red blood cell. 00:27:39.824 --> 00:27:42.702 So that's why if there is a relative access 00:27:42.702 --> 00:27:45.747 of any of these alpha beta, the first, 00:27:45.914 --> 00:27:48.833 the relative axis of the other one 00:27:48.833 --> 00:27:52.253 is basically freely circulating in the, blood. 00:27:52.545 --> 00:27:56.383 And it causes it binds to the red blood cell membrane and causes 00:27:56.383 --> 00:27:59.928 hemolytic anemia or basically breaks down the red blood cells. 00:28:00.637 --> 00:28:04.516 So it's thalassemia is a quantitative, problem. 00:28:04.516 --> 00:28:10.146 It's, it's it's due to low production of either alpha or beta globin chains. 00:28:10.772 --> 00:28:14.359 And it's same for the chain which is decreased or absent. 00:28:14.567 --> 00:28:19.614 So alpha thalassemia is defined by decreased alpha or absent alpha 00:28:20.198 --> 00:28:25.203 and beta thalassemia are defined by decreased or option beta. 00:28:26.037 --> 00:28:29.457 There are two different are signs which we always see 00:28:29.457 --> 00:28:32.711 in the thalassemia diagnosis beta plus 00:28:33.336 --> 00:28:36.339 or beta zero or alpha plus or alpha zero 00:28:36.756 --> 00:28:41.302 plus means there is some production of that particular chain. 00:28:42.220 --> 00:28:46.933 It could be either 5% or it could be 45%. 00:28:47.225 --> 00:28:50.895 So there is a reduction in the production, but still there 00:28:50.895 --> 00:28:52.522 is some production going on. 00:28:53.773 --> 00:28:55.567 Like if it's 00:28:55.567 --> 00:28:57.819 it's beta plus means 00:28:57.819 --> 00:29:01.364 there is a decrease in the production of beta chain, 00:29:01.740 --> 00:29:07.120 but if we unless we know the genetic, etiology behind the beta 00:29:07.120 --> 00:29:10.540 plus thalassemia, it's hard to predict the phenotype. 00:29:10.874 --> 00:29:15.044 So beta plus could mean that there is a reduction of 10%. 00:29:15.044 --> 00:29:18.673 Or it could also mean that there could be a reduction of 40%. 00:29:18.965 --> 00:29:23.678 So there's a lot of genetic heterogeneity behind the beta plus. 00:29:23.678 --> 00:29:25.513 But it basically simply means 00:29:25.513 --> 00:29:29.100 that there is a reduction in the production of that particular gene. 00:29:29.809 --> 00:29:34.481 Zero indicates complete absence of production. 00:29:34.481 --> 00:29:37.609 So if it's a beta zero, that means that beta 00:29:39.194 --> 00:29:41.362 alli is basically not functioning 00:29:41.362 --> 00:29:44.365 and not producing any beta chain. 00:29:44.616 --> 00:29:48.077 So that's the basic definition of thalassemia plus. 00:29:48.077 --> 00:29:50.538 And B plus and zero 00:29:51.623 --> 00:29:53.583 demographics, as I said earlier. 00:29:53.583 --> 00:29:56.836 Also it's very very important for the thalassemia diagnosis. 00:29:58.421 --> 00:30:01.424 It's very prevalent in certain part of the world 00:30:02.133 --> 00:30:05.220 most frequently seen in the Mediterranean population 00:30:05.220 --> 00:30:09.265 African, Western and Southeast Asia, India and Burma. 00:30:09.641 --> 00:30:12.268 One of the interesting point about 00:30:12.268 --> 00:30:15.271 thalassemia is its distribution 00:30:15.647 --> 00:30:18.650 to, Palace, that of the Plasmodium falciparum. 00:30:19.943 --> 00:30:22.946 Most of the time thalassemia, 00:30:23.112 --> 00:30:24.823 sickle cell anemia, sickle cell 00:30:24.823 --> 00:30:29.828 trait d6, PD, glucose six phosphate dehydrogenase deficiency, 00:30:29.828 --> 00:30:32.831 which we'll talk later in in this talk 00:30:32.831 --> 00:30:35.834 these all these 00:30:35.917 --> 00:30:37.669 again has 00:30:37.669 --> 00:30:41.172 the distribution parallels that of the Plasmodium falciparum. 00:30:42.298 --> 00:30:46.719 And the theory is the patients with thalassemia trait or sickle cell 00:30:46.719 --> 00:30:49.764 trait the size of the red blood cells are smaller 00:30:49.764 --> 00:30:53.726 or atypical or abnormal in these particular traits 00:30:54.310 --> 00:30:58.898 show the Plasmodium falciparum or the or the malaria. 00:30:59.232 --> 00:31:00.733 The bad form of the malaria. 00:31:02.527 --> 00:31:03.444 They could not 00:31:03.444 --> 00:31:07.198 survive that well compared to the normal red blood cells. 00:31:07.574 --> 00:31:11.369 So that's why these patients who have had some kind 00:31:11.369 --> 00:31:14.497 of a thalassemia trait or sickle cell trait, 00:31:14.789 --> 00:31:19.544 they have been selected out over like 10,000 years. 00:31:19.794 --> 00:31:22.797 So this population has had basically, 00:31:25.300 --> 00:31:27.719 genetic advantage over 00:31:27.719 --> 00:31:31.389 other population which didn't have these traits like thalassemia trait. 00:31:31.764 --> 00:31:36.728 So as I said, these patients who had not, micro cystic anemia in thalassemia 00:31:36.978 --> 00:31:41.858 or sickle cell trait that the red blood cells had cycling, cycles. 00:31:42.066 --> 00:31:45.612 So the Plasmodium falciparum or the malaria 00:31:46.029 --> 00:31:49.032 malarial, parasite could not survive that. 00:31:49.032 --> 00:31:52.118 Well, so that's why these patients have been selected out, 00:31:52.118 --> 00:31:55.121 because these patients could basically sustain this, 00:31:55.622 --> 00:31:58.625 malarial parasite much better than the normal cells. 00:31:58.917 --> 00:32:02.587 So it's very common to see the distribution goes 00:32:02.587 --> 00:32:05.590 very well along with the malarial parasite. 00:32:08.927 --> 00:32:10.178 So distinguishing 00:32:10.178 --> 00:32:13.181 feature between iron deficiency and thalassemia. 00:32:14.349 --> 00:32:17.602 As I said earlier, the common differential diagnosis 00:32:17.602 --> 00:32:22.148 for anemia is iron deficiency anemia. 00:32:22.148 --> 00:32:23.232 And thalassemia. 00:32:23.232 --> 00:32:26.653 And also any male chronic disorder which we just talked about. 00:32:28.321 --> 00:32:32.617 But iron deficiency and thalassemia, there are a lot of parameters 00:32:32.617 --> 00:32:36.621 which can be similar when we when we look at the CBC, 00:32:37.330 --> 00:32:39.666 however, certain parameters 00:32:39.666 --> 00:32:42.669 can be helpful in the differential diagnosis. 00:32:44.504 --> 00:32:48.091 In in the, iron deficiency anemia, 00:32:49.133 --> 00:32:51.886 the red blood cell count 00:32:51.886 --> 00:32:57.225 is usually less than 5 or 10 to power six microliter. 00:32:57.225 --> 00:33:01.187 So usually in cases of iron deficiency anemia, 00:33:01.521 --> 00:33:06.150 it's number of red blood cells because it's a nutritional cause of, 00:33:06.734 --> 00:33:10.530 anemia, the number of red blood cells are usually 00:33:10.530 --> 00:33:13.950 either normal or in the lower range of normal. 00:33:14.534 --> 00:33:15.284 However, 00:33:16.703 --> 00:33:17.078 the red 00:33:17.078 --> 00:33:23.626 blood cell count in color seems more than or in the higher range of normal. 00:33:23.835 --> 00:33:26.796 If you look at the reference range in the CBC, 00:33:28.172 --> 00:33:31.050 that's like one of the 00:33:31.050 --> 00:33:33.553 one of the common or important parameters. 00:33:33.553 --> 00:33:38.641 And when we try to distinguish between iron deficiency and thalassemia, 00:33:39.517 --> 00:33:43.187 because the MCB can be very similar, between 00:33:43.187 --> 00:33:47.442 both of these, the mean cell volume sometimes can have a lot of overlap. 00:33:47.859 --> 00:33:50.611 However, in thalassemia is usually 00:33:50.611 --> 00:33:53.614 the MCV is less than 70. 00:33:54.073 --> 00:33:57.076 In iron deficiency anemia, it's usually 00:33:57.118 --> 00:34:01.914 either more than 70 or in kind of in the lower range of normal 00:34:02.665 --> 00:34:05.710 red cell distribution with or RTW. 00:34:06.711 --> 00:34:09.714 In iron, deficiency anemia is usually 00:34:10.715 --> 00:34:12.759 more than the normal reference range 00:34:12.759 --> 00:34:16.554 or in the higher range of normal in the thalassemia. 00:34:16.554 --> 00:34:21.642 Because it's a genetic disorder, there's nothing to do with the nutrition here. 00:34:21.642 --> 00:34:24.645 It's a genetically acquired disorder. 00:34:24.687 --> 00:34:29.317 So once the red blood cell or the DNA has 00:34:29.317 --> 00:34:32.320 the mutations is going to remain forever. 00:34:32.737 --> 00:34:37.992 So the size of the red blood cells basically remains of the same size 00:34:37.992 --> 00:34:39.035 all the time. 00:34:39.035 --> 00:34:44.874 So the red cell distribution, which basically which tells us about the range 00:34:44.874 --> 00:34:50.922 of the size of the red blood cell is usually normal in cases of thalassemia. 00:34:52.215 --> 00:34:52.840 So if 00:34:52.840 --> 00:34:56.385 we if we can remember these three parameters 00:34:56.677 --> 00:35:00.014 when we are looking at the CBC, I would say 00:35:00.640 --> 00:35:04.018 more than in 90 to 95% of the cases, 00:35:04.018 --> 00:35:08.022 we should be able to make a good estimate 00:35:08.022 --> 00:35:11.025 about iron deficiency versus thalassemia. 00:35:11.317 --> 00:35:15.822 Most of the time when we are looking at the iron deficiency anemia, 00:35:15.822 --> 00:35:18.950 I would see a red blood cell in the lower 00:35:18.950 --> 00:35:21.953 range of normal or less than normal 00:35:22.495 --> 00:35:26.165 MCB, around 75 or 76, 00:35:26.707 --> 00:35:31.087 and red or blue in the range of 17 or 18 or something like that. 00:35:31.838 --> 00:35:34.966 In thalassemia, however, it's not uncommon 00:35:34.966 --> 00:35:37.969 to see a red blood cell of either 00:35:38.678 --> 00:35:41.681 normal or higher range of normal 00:35:41.681 --> 00:35:44.684 and MCB of 65 or 60. 00:35:45.226 --> 00:35:48.271 So these three parameters in my day to day 00:35:48.271 --> 00:35:52.567 practice is really, really helpful in making a diff. 00:35:52.567 --> 00:35:55.987 Coming up with a differential between iron deficiency and thalassemia, 00:35:56.279 --> 00:36:00.324 there could be some overlap in about maybe around 5% of the cases, 00:36:00.700 --> 00:36:04.871 but majority of the time I would say we can make a good estimate. 00:36:04.871 --> 00:36:07.874 A good guess about what kind of anemia is 00:36:09.667 --> 00:36:12.670 some of the pediatric hematologist? 00:36:14.255 --> 00:36:17.675 Most of the time pediatric pediatric hematologist or the 00:36:18.176 --> 00:36:20.803 or the hematologist were basically 00:36:20.803 --> 00:36:23.806 taking care of the kid with a plasma. 00:36:24.432 --> 00:36:28.936 They usually use some of the parameters of the index, 00:36:29.061 --> 00:36:32.064 basically to come up with the differential 00:36:32.190 --> 00:36:34.901 between iron deficiency and thalassemia. 00:36:34.901 --> 00:36:37.904 So it basically it means that, 00:36:39.363 --> 00:36:41.032 indexes were one of the common 00:36:41.032 --> 00:36:44.744 commonly used index in the pediatric world. 00:36:45.328 --> 00:36:48.706 And if the the ratio between MCV 00:36:49.081 --> 00:36:53.753 and red blood cell count is less than 13, it favors color. 00:36:53.753 --> 00:36:56.214 Female 00:36:56.214 --> 00:37:00.509 for practical purposes for like day to day practice, 00:37:00.509 --> 00:37:04.889 I really don't use this index or determine the ratio. 00:37:05.097 --> 00:37:09.727 Basically, this ratio is telling me that in cases of thalassemia, 00:37:09.977 --> 00:37:13.272 the red blood cell is either normal 00:37:13.272 --> 00:37:18.236 or in the higher range of normal, and MTV is like in the lower range of normal 00:37:18.611 --> 00:37:21.489 or much lower compared to the red cell. 00:37:21.489 --> 00:37:26.160 So most of the time it's not really required to go and make that ratio. 00:37:26.369 --> 00:37:30.248 If we carefully look at the three parameters, as I mentioned earlier, 00:37:30.581 --> 00:37:33.584 RBC, MCV and the RW, 00:37:33.751 --> 00:37:37.338 we should be able to make, good calculated Argus. 00:37:37.755 --> 00:37:42.468 But, these are some of the commonly used index, which 00:37:43.719 --> 00:37:46.264 we might encountered in our, 00:37:46.264 --> 00:37:49.267 differential diagnosis. 00:37:50.184 --> 00:37:52.186 Anemia of chronic disease. 00:37:52.186 --> 00:37:56.899 This is also, as I mentioned earlier, it's like one of the differential. 00:37:56.899 --> 00:38:00.820 And in the, microsatellite hyper chromic anemia, 00:38:02.571 --> 00:38:06.826 it can cause mild to moderate anemia due to increased side in. 00:38:06.826 --> 00:38:11.580 And I'm not going to go over in detail about the side in which is like the iron, 00:38:12.206 --> 00:38:18.212 the molecule for the iron transport and a lot of research going on. 00:38:18.212 --> 00:38:21.215 And basically determining, 00:38:21.465 --> 00:38:25.261 the utility and the mechanism 00:38:26.053 --> 00:38:29.265 why iron is absorbed much 00:38:29.765 --> 00:38:32.852 in higher quantity in anemia of chronic disorders, 00:38:32.852 --> 00:38:36.689 like in chronic infections, college and vascular disease and malignancy. 00:38:37.023 --> 00:38:39.817 People are still researchers are still trying 00:38:39.817 --> 00:38:44.530 to understand why that happens, why in these chronic immune 00:38:44.947 --> 00:38:51.329 mediated diseases, we have higher, uptake or storage of iron. 00:38:52.121 --> 00:38:54.665 So what happens in this, as I mentioned earlier, 00:38:55.833 --> 00:38:58.836 the storage form of iron is really high. 00:38:58.919 --> 00:39:02.214 But we cannot really utilize that iron. 00:39:02.214 --> 00:39:06.469 So the body has lot of iron in the stored form like in macrophages. 00:39:06.927 --> 00:39:10.056 So we look at the bone marrow or spleen. 00:39:10.514 --> 00:39:13.017 We'll see a lot of stored form of iron. 00:39:13.017 --> 00:39:19.065 But for some reason the, the, the the, the physiology of the iron is messed up 00:39:19.065 --> 00:39:23.903 so much that we cannot really utilize that stored form of iron. 00:39:24.445 --> 00:39:28.199 So if we look at the serum, serum iron or the peripheral iron, 00:39:29.533 --> 00:39:32.620 in the blood, that is usually decreased. 00:39:32.620 --> 00:39:34.622 So that's why anemia of chronic disease 00:39:34.622 --> 00:39:38.250 come under under the differential of iron deficiency anemia. 00:39:38.459 --> 00:39:43.047 Because you we will see decreased serum iron in both these conditions 00:39:43.297 --> 00:39:47.468 in iron deficiency anemia and as well as in anemia chronic disease. 00:39:47.676 --> 00:39:50.179 So the serum iron is decreased. 00:39:50.179 --> 00:39:55.184 But the storage form of iron for some mechanism is increased. 00:39:55.184 --> 00:39:56.685 And we are still the researchers 00:39:56.685 --> 00:40:01.107 and researchers are still trying to understand why that happens. 00:40:01.315 --> 00:40:06.320 And when one of the key molecules is the side in which is the most important 00:40:06.570 --> 00:40:11.409 molecule to basically observe 00:40:11.409 --> 00:40:15.204 iron from the, duodenum or the small intestine. 00:40:15.454 --> 00:40:20.334 So the website, it plays a very key important role in the iron absorption. 00:40:20.626 --> 00:40:23.629 And, that's why the, 00:40:23.796 --> 00:40:26.632 in cases of anemia, of chronic disease, 00:40:26.632 --> 00:40:30.010 we see increased storage form of iron. 00:40:30.010 --> 00:40:34.974 But the entire pathophysiology and the mechanism is still kind of obscure. 00:40:34.974 --> 00:40:38.978 And I do suggest that researchers are still trying to understand that. 00:40:40.896 --> 00:40:43.899 So that was about my prosthetic anemia. 00:40:44.400 --> 00:40:47.403 I hope I gave you, 00:40:47.820 --> 00:40:49.363 the common parameters 00:40:49.363 --> 00:40:54.702 and the common, diagnostic features, which can help us in 00:40:55.119 --> 00:40:58.122 coming up with a differential of micro Citic anemia. 00:40:58.873 --> 00:41:02.793 So let's talk about macro Citic anemia, which basically 00:41:02.793 --> 00:41:06.714 means the size of the red blood cells are much bigger. 00:41:06.714 --> 00:41:10.050 So our reference range is about 80 to 100. 00:41:10.426 --> 00:41:14.388 Here in macro Citic anemia is usually more than 100. 00:41:16.265 --> 00:41:20.686 And the pathophysiology behind macro Citic anemia is 00:41:21.103 --> 00:41:26.317 that there is a problem in the DNA synthesis in the red blood cell. 00:41:26.984 --> 00:41:30.988 And the most common cause of macro Citic 00:41:31.030 --> 00:41:34.033 anemia is vitamin B12 deficiency 00:41:34.366 --> 00:41:37.369 and folate deficiency. 00:41:37.411 --> 00:41:39.580 Both of these folate and cobalt 00:41:39.580 --> 00:41:43.417 or vitamin B12 are required for the DNA synthesis. 00:41:43.751 --> 00:41:49.340 So that's why if there is a deficiency of any of these folate or vitamin B12, 00:41:49.840 --> 00:41:53.260 it basically causes problems with the DNA synthesis. 00:41:54.011 --> 00:41:56.889 So as we might recall, 00:41:56.889 --> 00:42:00.684 DNA synthesis not only happens in the red blood cell. 00:42:00.684 --> 00:42:04.939 Precursor is not really only important for red blood cell precursors. 00:42:05.439 --> 00:42:09.860 It's all it's important for all the, cells of the human body. 00:42:10.236 --> 00:42:14.990 So in cases of macro Citic anemia, not only red 00:42:14.990 --> 00:42:18.994 blood cells or its precursors means like immature red blood cells 00:42:19.870 --> 00:42:23.582 which have DNA, nucleus and have DNA are affected. 00:42:24.166 --> 00:42:27.044 But also the leukocytes, 00:42:27.044 --> 00:42:31.715 the WBC and platelets are also affected. 00:42:31.840 --> 00:42:36.220 So that's why it's in cases of macro Citic anemia. 00:42:36.512 --> 00:42:39.515 All these three parameters are affected. 00:42:39.515 --> 00:42:45.354 So not only we see anemia, we also see a decrease in WBC and decrease in places. 00:42:45.854 --> 00:42:49.066 So decrease in WBC is known as leukemia. 00:42:49.358 --> 00:42:53.195 And decrease in platelets is known as thrombocytopenia. 00:42:53.195 --> 00:42:54.572 So we see basically 00:42:54.572 --> 00:42:58.867 and if all these three parameters are affected it's known as pan cytokine. 00:42:58.867 --> 00:42:59.118 Yeah. 00:43:00.578 --> 00:43:03.038 So it's not uncommon to see 00:43:03.038 --> 00:43:06.625 all these three parameters affected in both these conditions. 00:43:07.459 --> 00:43:10.546 Deficiency results in megalo blast anemia. 00:43:10.546 --> 00:43:15.301 So megalo means really big and plastic means immature cells. 00:43:15.676 --> 00:43:19.805 So it leads to because of the problem with the DNA synthesis, 00:43:20.139 --> 00:43:24.310 it leads to the cells become much larger in size. 00:43:25.060 --> 00:43:30.608 And since the DNA is not really, forming that well, 00:43:30.983 --> 00:43:34.612 the nucleus of the red blood cells remain very immature. 00:43:34.612 --> 00:43:36.113 They do not mature. 00:43:36.113 --> 00:43:40.367 So that's that's what basically the definition of megalo aplastic 00:43:40.367 --> 00:43:44.663 anemia is due to the impaired DNA replication 00:43:45.164 --> 00:43:50.085 leads to impaired nuclear development because DNA obviously is not formed. 00:43:50.419 --> 00:43:54.423 So the DNA of the nucleus would remain very immature. 00:43:54.757 --> 00:43:57.760 However the cytoplasm of the cell would be mature. 00:43:57.760 --> 00:44:02.514 So that's what it means by nuclear cytoplasmic asynchrony. 00:44:02.765 --> 00:44:07.853 So that means the nucleus is basically lagging behind in maturation. 00:44:08.145 --> 00:44:10.522 The cytoplasm is really matured well. 00:44:10.522 --> 00:44:13.067 But the nuclei is kind of immature. 00:44:13.067 --> 00:44:15.402 And it's very commonly seen in 00:44:16.570 --> 00:44:18.447 Mikala plastic anemia or in 00:44:18.447 --> 00:44:21.533 anemia due to folate or vitamin B12 deficiency. 00:44:22.993 --> 00:44:27.289 Because the DNA is not really functioning that well, the size of the red blood 00:44:27.289 --> 00:44:32.628 cell culture, also known as progenitors, marrow progenitors, are much larger 00:44:32.628 --> 00:44:35.798 compared to the normal, red blood cell because it 00:44:37.508 --> 00:44:41.345 the features, the clinical features or the clinical manifestations 00:44:41.345 --> 00:44:45.724 of these both these disorders are very similar. 00:44:46.934 --> 00:44:49.937 However, there's one exception. 00:44:50.020 --> 00:44:53.440 Neurological abnormalities are seen in vitamin 00:44:53.440 --> 00:44:56.443 B12 deficiency, but not in folate, 00:44:56.443 --> 00:44:59.113 because in vitamin B12 00:44:59.113 --> 00:45:03.534 is also important for generation of the myelin, 00:45:03.826 --> 00:45:09.331 which is the outer covering of the nervous system or the neurons. 00:45:09.665 --> 00:45:14.002 So that's why there is a vitamin B12 deficiency that the outer 00:45:14.002 --> 00:45:17.923 covering of the neurons, the myelin, is not formed that well. 00:45:18.424 --> 00:45:22.594 And that leads to neurological abnormalities in B12 deficiency. 00:45:23.679 --> 00:45:26.348 However, folate that doesn't happen in followed 00:45:26.348 --> 00:45:30.018 because it is not really required for the myelin generation. 00:45:30.894 --> 00:45:34.606 But apart from that, neurological abnormalities, 00:45:35.107 --> 00:45:37.943 which are three of the features, are similar 00:45:37.943 --> 00:45:40.946 in both these conditions. 00:45:44.324 --> 00:45:47.161 So the clinical and laboratory findings, 00:45:47.161 --> 00:45:50.414 there are a lot of nonspecific signs and symptoms of anemia 00:45:50.456 --> 00:45:54.585 like fatigue, tiredness, failure to thrive, 00:45:55.002 --> 00:45:57.796 macro anemia, 00:45:57.796 --> 00:46:00.591 relatively low reticular site count. 00:46:00.591 --> 00:46:03.844 As I mentioned earlier, the reticular site count 00:46:03.844 --> 00:46:07.264 basically reflects the functioning of the bone marrow. 00:46:07.639 --> 00:46:11.685 Since this is not really, nutritional problem. 00:46:12.603 --> 00:46:14.813 It basically 00:46:14.813 --> 00:46:19.359 it it affects pretty much all the, cells. 00:46:19.359 --> 00:46:23.489 So that that basically leads to low reticular site count. 00:46:23.864 --> 00:46:26.867 In the, in the, 00:46:26.950 --> 00:46:29.953 sorry, in the, basal circulation, 00:46:30.579 --> 00:46:33.582 the one of the important, 00:46:33.791 --> 00:46:36.251 diagnostic feature of macroscopic 00:46:36.251 --> 00:46:39.797 anemia is hyper segmentation of neutrophils. 00:46:40.172 --> 00:46:43.425 So because of the derangement of the DNA 00:46:43.425 --> 00:46:48.388 synthesis, the segmentation of neutrophils is not like 00:46:48.388 --> 00:46:52.768 a normal segmentation, which is about 3 to 4 or 3 to 5 loads 00:46:54.186 --> 00:46:57.606 in cases of, macro static anemia, 00:46:57.606 --> 00:47:01.235 the segmentation could be much more than the normal segmentation. 00:47:01.527 --> 00:47:05.447 And this is one of the earliest finding of macroscopic anemia. 00:47:05.447 --> 00:47:09.117 So when we are looking at the peripheral blood smear 00:47:10.202 --> 00:47:12.246 and we see a patient 00:47:12.246 --> 00:47:15.249 with increased MCV or metastatic anemia, 00:47:16.124 --> 00:47:18.252 we try to find hyper segmented 00:47:18.252 --> 00:47:21.880 neutrophils and hyper segmented neutrophils. 00:47:21.880 --> 00:47:24.883 Basically that kind of. 00:47:25.634 --> 00:47:28.178 It's like one to not like 00:47:28.178 --> 00:47:32.391 it's not the most specific feature for macro anemia. 00:47:32.391 --> 00:47:34.601 But if we can see hyper segmented neutrophils 00:47:34.601 --> 00:47:37.604 is really helpful for the diagnostic purpose. 00:47:37.688 --> 00:47:42.067 Mild thrombocytopenia decrease in platelets or neutropenia. 00:47:42.067 --> 00:47:46.905 As I said earlier, it's because DNA synthesis is not only required 00:47:46.905 --> 00:47:47.656 for the red blood 00:47:47.656 --> 00:47:51.535 cell precursors, it's also important for platelets and neutropenia. 00:47:51.535 --> 00:47:54.454 So all the three lineages are affected. 00:47:54.454 --> 00:47:56.874 Bigalow plastic changes in marrow is common. 00:47:58.000 --> 00:48:00.085 Neurological findings B12 00:48:00.085 --> 00:48:03.922 is only seen in B12 deficiency like loss of production. 00:48:03.922 --> 00:48:06.091 Since axilla, 00:48:06.091 --> 00:48:08.218 psychomotor retardation and seizures, 00:48:08.218 --> 00:48:11.346 so these are commonly seen in vitamin B12 deficiency. 00:48:13.223 --> 00:48:16.810 These this is an example of hyper segmented neutrophils. 00:48:17.144 --> 00:48:23.901 So here there are at least 123467 segments of neutrophils. 00:48:24.192 --> 00:48:27.195 Usually we see around 3 to 5 00:48:27.905 --> 00:48:28.238 here. 00:48:28.238 --> 00:48:32.910 Also this is a somewhat immature neutrophils. 00:48:33.076 --> 00:48:35.913 But the segmentation is again very atypical. 00:48:35.913 --> 00:48:38.373 And here. 00:48:38.373 --> 00:48:41.752 Megalo plastic changes in the precursor of the red blood cell. 00:48:42.002 --> 00:48:46.131 So it basically shows a giant Mylo site. 00:48:47.549 --> 00:48:48.967 These two. 00:48:48.967 --> 00:48:51.219 So it's it's basically the nuclei. 00:48:51.219 --> 00:48:54.222 If we look at the nuclei it is very, very immature. 00:48:54.222 --> 00:48:57.100 The chromatin is kind of dispersed. 00:48:57.100 --> 00:48:59.102 However the cytoplasm is bluish. 00:48:59.102 --> 00:49:02.147 So that means the cytoplasm is kind of mature. 00:49:02.147 --> 00:49:04.691 But the nuclei is looks very very immature. 00:49:07.194 --> 00:49:09.613 So that's like a basic 00:49:09.613 --> 00:49:12.699 work of, of macro anemia. 00:49:13.992 --> 00:49:15.827 Let's talk about normal Citic anemia, 00:49:15.827 --> 00:49:20.999 which is the the most, most of the anemia in our day to day 00:49:20.999 --> 00:49:24.002 practice would come under normal acidic anemia. 00:49:24.586 --> 00:49:26.421 Category 00:49:26.421 --> 00:49:29.716 differential diagnosis of normal Citic anemia is 00:49:31.593 --> 00:49:32.678 based upon B. 00:49:32.678 --> 00:49:37.307 Basically, there is a big list of normal Citic anemia. 00:49:37.307 --> 00:49:40.602 So anything that doesn't come under micro Citic anemia 00:49:40.602 --> 00:49:43.605 and macro Citic anemia would come under normal civic anemia. 00:49:43.730 --> 00:49:47.859 So the list of the normal Citic anemia is really huge. 00:49:48.318 --> 00:49:52.656 So basically we try to put that put 00:49:52.948 --> 00:49:56.159 normal Citic anemia in two major categories. 00:49:56.535 --> 00:49:59.371 Whether the bone marrow is functioning or not functioning. 00:49:59.371 --> 00:50:02.916 So that means if the reticular sites are increased in number 00:50:03.041 --> 00:50:05.127 that means the bone marrow is functioning. 00:50:05.127 --> 00:50:09.047 So the most common causes of increased red Citic 00:50:09.089 --> 00:50:14.511 anemia would be hemolytic anemia or post hemorrhagic anemia or anemia. 00:50:14.511 --> 00:50:16.263 After bleeding. 00:50:16.263 --> 00:50:19.307 If this if we see the reticular sites are decreased, 00:50:19.307 --> 00:50:23.770 or the percentage of reticular sites are lower than the normal reference range, 00:50:24.062 --> 00:50:27.315 there is again a big list of causes 00:50:27.315 --> 00:50:31.028 which can cause from acidic anemia with decreased reticular sites. 00:50:31.653 --> 00:50:35.866 Anemia of chronic disorders can also come under this category. 00:50:36.158 --> 00:50:38.744 Lot of endocrine disease, liver disease, 00:50:39.703 --> 00:50:42.039 marrow infiltration 00:50:42.039 --> 00:50:45.042 minor dysplastic syndrome, which is like, 00:50:45.959 --> 00:50:48.045 kind of a cancer of the bone 00:50:48.045 --> 00:50:51.214 marrow precursors, hyperplastic anemia. 00:50:51.214 --> 00:50:52.883 That means aplastic anemia. 00:50:52.883 --> 00:50:55.719 So that means the bone marrow is not functioning, whether it's 00:50:55.719 --> 00:50:59.222 because of the vital, in fact, infection or some kind of an insult. 00:50:59.681 --> 00:51:04.770 So the list for the normal Citic anemia with decreased sites is really huge. 00:51:05.187 --> 00:51:09.316 So evaluation of normal static anemia, 00:51:09.316 --> 00:51:12.861 we try to look at the peripheral smear and come up with critical side count. 00:51:14.196 --> 00:51:16.198 And then if theoretical side count 00:51:16.198 --> 00:51:21.078 as as I mentioned earlier is decreased, then we need to work up 00:51:21.078 --> 00:51:25.248 for the anemia of all the endocrine diseases, renal disease, liver disease. 00:51:25.957 --> 00:51:29.711 If the Red cross site counts are increased, that that means 00:51:30.670 --> 00:51:34.466 the red blood cells are destroyed in the peripheral circulation 00:51:35.092 --> 00:51:37.761 due to various reason. 00:51:37.761 --> 00:51:41.098 It could be due to some kind of a viral infection, or it could be 00:51:41.098 --> 00:51:44.476 some kind of auto antibodies against the red blood cells. 00:51:44.768 --> 00:51:50.065 So, there is again, a big list for the causes of hemolytic anemia. 00:51:51.024 --> 00:51:52.567 Sometimes, 00:51:52.567 --> 00:51:56.196 iron studies might be helpful to, to rule out because some of the iron 00:51:56.446 --> 00:52:00.659 iron, deficiency anemia can also come under the normal Citic anemia, 00:52:00.659 --> 00:52:03.703 especially the borderline category of iron deficiency anemia. 00:52:03.995 --> 00:52:08.083 So if the iron parameters are completely on low, that really would 00:52:08.083 --> 00:52:11.920 help, to diagnose borderline causes of, 00:52:12.462 --> 00:52:14.923 iron deficiency anemia. 00:52:14.923 --> 00:52:18.593 If all these parameters fail, then the bone 00:52:18.593 --> 00:52:21.596 marrow biopsy would be the ultimate, 00:52:21.763 --> 00:52:23.056 diagnostic. 00:52:23.056 --> 00:52:24.975 Feature. 00:52:24.975 --> 00:52:27.060 Especially in cases of, 00:52:27.060 --> 00:52:31.356 some of the marrow infiltration, anemia and aplastic 00:52:31.356 --> 00:52:35.235 anemia, bone marrow becomes absolutely necessary for that diagnosis. 00:52:35.735 --> 00:52:38.196 That diagnosis. 00:52:38.196 --> 00:52:39.406 Okay. 00:52:39.406 --> 00:52:43.410 So hemolytic anemia, as is a major category for 00:52:44.202 --> 00:52:47.038 normal static anemia with increase reticular sites 00:52:47.038 --> 00:52:49.416 basically means the bone marrow is functioning. 00:52:49.416 --> 00:52:52.711 Again, it can be divided into inherited hemolytic anemia. 00:52:52.711 --> 00:52:54.921 And acquired hemolytic anemia. 00:52:54.921 --> 00:52:58.925 And I don't have time to go over in detail about all these causes. 00:52:58.925 --> 00:53:03.138 But I will basically try to give a basic outline 00:53:03.138 --> 00:53:06.766 of the causes of these inherited hemolytic anemia. 00:53:07.058 --> 00:53:12.230 The most common causes are membrane defects, hereditary status psychosis. 00:53:12.230 --> 00:53:12.981 I'll talk a little bit 00:53:12.981 --> 00:53:17.068 about hereditary state of psychosis because it's a relatively common disorder. 00:53:17.569 --> 00:53:18.653 Globin defects. 00:53:19.779 --> 00:53:20.947 Like thalassemia 00:53:20.947 --> 00:53:23.867 or sickle cell anemia can also come under this category. 00:53:23.867 --> 00:53:26.620 Most of the time, sickle cell anemia, 00:53:26.620 --> 00:53:29.748 metabolic disorder like enzyme deficiency, glucose six 00:53:29.748 --> 00:53:32.751 phosphate deficiency is one of the commonest deficiency 00:53:33.126 --> 00:53:36.129 of the enzyme, which can cause hemolytic anemia, 00:53:36.338 --> 00:53:39.424 so these are the inherited hemolytic causes 00:53:39.424 --> 00:53:42.427 of inherited hemolytic anemia. 00:53:42.636 --> 00:53:44.471 Hereditary spell psychosis 00:53:44.471 --> 00:53:49.267 is the most common cause of hereditary hemolytic anemia. 00:53:50.227 --> 00:53:53.730 The red blood cells are smaller in size. 00:53:53.730 --> 00:53:56.733 They are smaller microscopic, but they're not like, 00:53:56.983 --> 00:54:00.737 the hemoglobin is normal in other. 00:54:01.029 --> 00:54:02.697 So they are microscopic status. 00:54:02.697 --> 00:54:06.076 The size of the red blood cells are kind of smaller, 00:54:06.326 --> 00:54:09.120 but the hemoglobin is normal in, in there. 00:54:09.120 --> 00:54:13.208 So it's basically it's it's a smaller red. 00:54:13.667 --> 00:54:16.086 It's, it's a dense form of red blood cells. 00:54:16.086 --> 00:54:17.712 They're smaller, but very dense. 00:54:18.672 --> 00:54:19.839 The MTV is 00:54:19.839 --> 00:54:23.760 more or less kind of, normal usually mixes. 00:54:23.802 --> 00:54:27.555 So this is the one parameter where the MCC at C is 00:54:27.806 --> 00:54:30.809 one disease that at C can be helpful. 00:54:31.268 --> 00:54:34.271 So basically MCC at C is usually increased 00:54:34.479 --> 00:54:37.440 denoting that the size of the red blood 00:54:37.440 --> 00:54:40.443 cells are kind of smaller in size. 00:54:41.528 --> 00:54:43.780 Although the size of the red blood cells are smaller, 00:54:43.780 --> 00:54:46.783 the hemoglobin concentration is more or less normal. 00:54:47.742 --> 00:54:50.870 The inheritance pattern of the hereditary titles 00:54:50.954 --> 00:54:54.499 is in about 75% of the cases is articular dominant. 00:54:56.584 --> 00:55:00.130 It happens if we look at the genetic etiology. 00:55:00.130 --> 00:55:05.844 It happens due to mutation in the various structural membrane proteins 00:55:05.844 --> 00:55:09.306 or instead of the red blood cells, most commonly 00:55:09.306 --> 00:55:12.309 in the anchoring gene. 00:55:12.600 --> 00:55:15.603 And which 30 of them, 00:55:16.271 --> 00:55:19.107 status a hereditary status, say twosies. 00:55:19.107 --> 00:55:24.446 If the diagnosis is made and spleen is removed from the patient. 00:55:24.446 --> 00:55:27.907 Because spleen is the most common site 00:55:28.283 --> 00:55:31.286 for the destruction of the red blood cells. 00:55:31.619 --> 00:55:36.166 So because of the smaller size of the red blood cells and the condensed 00:55:36.166 --> 00:55:39.127 form, because of the skyrocketing form of the red blood cells, 00:55:39.461 --> 00:55:42.964 these red blood cells becomes much more kind of, 00:55:44.591 --> 00:55:45.800 tighter. 00:55:45.800 --> 00:55:48.887 They're not that flexible compared to the normal red blood cells. 00:55:49.095 --> 00:55:53.308 So they get destroyed easily in the capillary circulation. 00:55:53.641 --> 00:55:56.353 And the most common site for that is the spleen. 00:55:56.353 --> 00:56:00.815 So if we take out the spleen pretty much cured these patients. 00:56:01.149 --> 00:56:04.152 However, there might be something caution needed. 00:56:04.152 --> 00:56:06.696 Overall precaution after the splenectomy. 00:56:06.696 --> 00:56:09.366 So they might need, 00:56:09.366 --> 00:56:11.826 treatment or, 00:56:11.826 --> 00:56:16.539 for the some of the viral infection or some of the common anemia. 00:56:16.539 --> 00:56:21.419 But most of the time it's basically if we take out the spleen, it, it, 00:56:22.003 --> 00:56:25.006 basically cures heritage status like ptosis. 00:56:26.383 --> 00:56:28.843 This is what it looks like, official blood circulation. 00:56:28.843 --> 00:56:34.265 So the normal red blood cell would have a nice central pallor in the center. 00:56:35.016 --> 00:56:38.645 However, if you look at this photo sites, they are kind of smaller 00:56:38.645 --> 00:56:40.814 in size compared to the normal red blood cell. 00:56:40.814 --> 00:56:43.900 But also there is no central pallor. 00:56:43.900 --> 00:56:47.153 So these are basically condensed red blood cells. 00:56:47.320 --> 00:56:50.532 So that's why it becomes much more kind of tighter compared 00:56:50.532 --> 00:56:53.535 to the flexible, you know, red blood cells. 00:56:53.618 --> 00:56:55.662 And they're much more prone to destruction. 00:56:57.872 --> 00:56:59.666 How do we diagnose assess. 00:56:59.666 --> 00:57:01.376 They look at the peripheral blood smear. 00:57:01.376 --> 00:57:03.169 And we see a lot of cirrhosis. 00:57:03.169 --> 00:57:04.754 That's that's helpful. 00:57:04.754 --> 00:57:07.757 Although not diagnostic. 00:57:08.007 --> 00:57:11.052 Osmotic fragility is one of the common 00:57:11.428 --> 00:57:14.431 sensitive tests for the diagnosis of etches. 00:57:14.556 --> 00:57:18.643 It basically measures the in vitro lysis of the red blood cells 00:57:18.643 --> 00:57:23.231 that's been suspended in different solutions of sodium chloride 00:57:24.774 --> 00:57:25.191 status. 00:57:25.191 --> 00:57:29.737 Sites are characterized by the membrane loss, and they're basically less 00:57:29.737 --> 00:57:33.825 redundant to withstand the, increasing, decreasing osmolarity. 00:57:33.825 --> 00:57:37.912 So they they destroy much easier compared to the normal red blood cells. 00:57:38.621 --> 00:57:41.666 However, parasites are not osmotic 00:57:41.666 --> 00:57:45.044 fragility test is not specific for the diagnosis of HS. 00:57:45.545 --> 00:57:49.716 It only basically tells us that the patient has parasites. 00:57:49.716 --> 00:57:53.178 It doesn't tell us anything about the etiology of this parasite. 00:57:53.845 --> 00:57:57.640 So instead of signs can be seen not only in etches, 00:57:57.682 --> 00:58:01.644 but it can also be seen in certain other conditions like autoimmune 00:58:01.644 --> 00:58:04.522 hemolytic anemia. Bone patients 00:58:05.648 --> 00:58:07.442 can also have a slew of sites. 00:58:07.442 --> 00:58:11.029 So osmotic fragility only tells us about, 00:58:11.863 --> 00:58:15.658 the basic the feature that the patient has fatal sites. 00:58:15.825 --> 00:58:20.580 It doesn't basically tells us about the etiology of the change. 00:58:21.039 --> 00:58:23.333 As for the psychosis, 00:58:23.333 --> 00:58:25.376 this is what, 00:58:25.376 --> 00:58:27.629 basically 00:58:27.629 --> 00:58:30.048 the core for the schematic facility looks like 00:58:30.048 --> 00:58:32.926 in cases of, a normal red blood cells. 00:58:32.926 --> 00:58:34.677 This is, 00:58:34.677 --> 00:58:37.680 compared to the normal red blood cells, it has patients. 00:58:38.765 --> 00:58:40.934 Red blood cells basically gets destroyed. 00:58:40.934 --> 00:58:43.895 Is, usually compared to the normal red flashes. 00:58:43.895 --> 00:58:49.484 So in here and normally they would get destroyed at 0.5% saline. 00:58:49.484 --> 00:58:52.695 But the in cases of HSA patients, they would destroy that. 00:58:52.695 --> 00:58:55.657 Let's see 0.2 00:58:55.949 --> 00:58:58.952 less than the 0.5%. 00:59:00.370 --> 00:59:02.622 Flow cytometry is, 00:59:02.622 --> 00:59:06.751 the most sensitive and specific way for the diagnosis of HS 00:59:07.752 --> 00:59:09.128 because the the 00:59:09.128 --> 00:59:13.007 dye which we use here, it specifically binds to the red blood 00:59:13.007 --> 00:59:14.259 cell membrane. 00:59:14.259 --> 00:59:18.346 So if the flow cytometry is positive, 00:59:18.763 --> 00:59:22.100 that means that the patient has hereditary. 00:59:22.100 --> 00:59:28.064 This parasite ptosis is almost 97 to 98% specific and quite sensitive to. 00:59:28.064 --> 00:59:32.277 So this is becoming much more commoner and more kind of used. 00:59:32.277 --> 00:59:35.280 As for the diagnosis itself, heritage status ptosis. 00:59:37.657 --> 00:59:41.077 D6 PD glucose six phosphate deficiency. 00:59:41.494 --> 00:59:44.497 I'm just going to touch a little bit about this, 00:59:44.497 --> 00:59:48.668 because this is also one of the commonest cause of hemolytic anemia. 00:59:49.419 --> 00:59:53.798 This particular enzyme catalyzes the initial step in the pentose 00:59:53.798 --> 00:59:57.302 phosphate pathway, which is required for the energy generation. 00:59:57.802 --> 01:00:02.515 This is a X-linked disease, so boys or the males are affected. 01:00:02.557 --> 01:00:04.642 Females can be career. 01:00:04.642 --> 01:00:08.313 There are a lot of different variant or mutations have been described. 01:00:10.898 --> 01:00:13.610 It's commonly seen in African-American population 01:00:13.610 --> 01:00:17.405 about 35% in the Sardinian population, also seen in Asians. 01:00:17.655 --> 01:00:20.575 So this is again common in African population 01:00:20.575 --> 01:00:23.578 and some of the Mediterranean population to. 01:00:25.872 --> 01:00:27.457 The clinical presentation 01:00:27.457 --> 01:00:31.085 could be either acute acute acquired hemolytic anemia. 01:00:31.085 --> 01:00:36.466 So many of these patients or the mutation the patients having particular mutations 01:00:36.841 --> 01:00:41.596 are more prone to hemolysis or destruction of the red blood cells 01:00:41.888 --> 01:00:45.016 when they are exposed to certain drugs or certain 01:00:46.476 --> 01:00:48.936 like, certain, 01:00:48.936 --> 01:00:51.397 beads or dyes. 01:00:51.397 --> 01:00:55.276 So there is, again, a big list of, chemicals 01:00:55.276 --> 01:00:59.072 or dyes or drugs which can precipitate these patients. 01:00:59.656 --> 01:01:01.908 So these patients 01:01:01.908 --> 01:01:05.745 basically will have to avoid those certain drugs like fava beans is 01:01:05.745 --> 01:01:09.624 one of the common cause of precipitation in Mediterranean population. 01:01:10.208 --> 01:01:14.295 So if this patient had this PD deficiency they will have to avoid even some. 01:01:14.295 --> 01:01:17.423 Sometimes the smell and smell of the foul 01:01:17.423 --> 01:01:21.135 beans can also precipitate, hemolytic anemia. 01:01:22.178 --> 01:01:23.596 Many of the patients would 01:01:23.596 --> 01:01:28.643 have basically chronic mild hemolytic anemia all their lives in the physic. 01:01:28.643 --> 01:01:32.855 And the the phenotype or the clinical presentation depends 01:01:32.855 --> 01:01:35.858 upon the underlying mutation in these patients. 01:01:37.694 --> 01:01:38.903 This is 01:01:38.903 --> 01:01:41.406 this is a Heinz body test done in G6. 01:01:41.406 --> 01:01:46.202 PD is basically showing us the precipitated denatured hemoglobin here. 01:01:46.619 --> 01:01:49.122 So this is a supravit in the stain. 01:01:49.122 --> 01:01:52.875 And the patients with E6 PD deficiency because of the nature, 01:01:52.875 --> 01:01:56.045 because the G6, PD this particular enzyme is deficient. 01:01:56.045 --> 01:01:59.507 They are more prone to destruction precipitate 01:01:59.507 --> 01:02:01.592 precipitation of the hemoglobin. 01:02:01.592 --> 01:02:05.972 And this precipitated form of the hemoglobin can be can be seen by high 01:02:06.097 --> 01:02:07.056 bodies. 01:02:07.056 --> 01:02:10.268 Can be seen as Heinz Heinz bodies in to provide insulin. 01:02:10.727 --> 01:02:15.857 This is again not specific for d6 PD any condition where we have destruction 01:02:16.232 --> 01:02:21.279 of oxidized sorry stress leading to denatured hemoglobin would 01:02:22.697 --> 01:02:25.491 lead to formation of Heinz bodies. 01:02:25.491 --> 01:02:29.704 But in the right clinical scenario and clinical kind of manifestation, 01:02:29.704 --> 01:02:32.915 if we see Heinz bodies, that becomes kind of very helpful. 01:02:34.751 --> 01:02:37.336 These are by itself, 01:02:37.336 --> 01:02:40.339 this is like as the picture shown here 01:02:40.798 --> 01:02:43.760 looks like it has been taken up by it. 01:02:43.760 --> 01:02:46.763 So what happens when those, 01:02:48.765 --> 01:02:50.892 Heinz bodies, 01:02:50.892 --> 01:02:53.352 the, the macrophages 01:02:53.352 --> 01:02:58.608 or the scavenger cells in the spleen, they will try to take out 01:02:58.608 --> 01:03:03.529 this precipitated hemoglobin and the macrophages will take a bite. 01:03:03.529 --> 01:03:06.657 So this part of the red blood cell would be taken out. 01:03:07.658 --> 01:03:09.744 After that it basically looks like that. 01:03:09.744 --> 01:03:12.580 So there was a Heinz body precipitated hemoglobin. 01:03:12.580 --> 01:03:15.583 It has been taken out by the macrophages. 01:03:15.792 --> 01:03:17.877 And that's why it looks like white cells. 01:03:17.877 --> 01:03:21.005 So although it's commonly seen in this theory but again 01:03:21.005 --> 01:03:24.008 it's not diagnostic and not specific for it. 01:03:24.050 --> 01:03:25.551 But in again clinical right. 01:03:25.551 --> 01:03:28.596 Clinical scenario it's helpful test. 01:03:28.596 --> 01:03:31.599 They briefly for d6 PD deficiency. 01:03:32.558 --> 01:03:35.812 The bedside test is the fluorescent spot test. 01:03:36.229 --> 01:03:39.398 So these cards have d6 p which is the 01:03:40.691 --> 01:03:43.694 glucose six phosphate and and ADP 01:03:44.946 --> 01:03:48.491 basically detects the generation of nADPh from nADPh. 01:03:48.616 --> 01:03:52.328 So we need to put Nadp plus and B6 PD on this card. 01:03:52.745 --> 01:03:59.377 And if the basically if d6 PD is there, then nADPh is generated. 01:03:59.377 --> 01:04:04.090 And if there is no d6 PD then nADPh would not be generated. 01:04:05.258 --> 01:04:10.263 However, the caveat is it only detects the severe form of d6 pd. 01:04:10.471 --> 01:04:16.519 So enzyme levels has to be below 3,030% to be basically this these cards 01:04:16.519 --> 01:04:19.605 to be positive enzyme activity assays 01:04:19.605 --> 01:04:22.817 done in the majority of the big laboratories. 01:04:22.817 --> 01:04:25.987 It basically depends on the spectral photometric assay. 01:04:26.821 --> 01:04:30.408 It tells us about the the amount of enzyme present. 01:04:31.284 --> 01:04:33.786 However, all these non 01:04:33.786 --> 01:04:39.041 genetic or non PCR based test becomes really irrelevant 01:04:39.041 --> 01:04:42.044 if the patient has been recently transfused 01:04:42.753 --> 01:04:45.965 which is very common in cases of d6, PD deficiency 01:04:45.965 --> 01:04:50.344 because these patients would lead to acute like hemolysis 01:04:51.846 --> 01:04:53.264 after the transfusion. 01:04:53.264 --> 01:04:55.725 Obviously we won't be looking at the patients. 01:04:55.725 --> 01:04:58.352 Red blood cells will be looking at the transfused red blood cells. 01:04:58.352 --> 01:05:00.855 So these is, enzyme activity. 01:05:00.855 --> 01:05:03.858 Actually information spot is not that helpful. 01:05:04.775 --> 01:05:07.320 The PCR based test mutation testing 01:05:07.320 --> 01:05:10.531 for PCR becomes, important at that point. 01:05:10.531 --> 01:05:14.368 If we are trying to basically make a diagnosis immediately after hemolysis, 01:05:14.368 --> 01:05:18.080 or it's really helpful in prenatal diagnosis and genetic counseling, 01:05:19.040 --> 01:05:21.792 it will tell us about the about the mutation 01:05:21.792 --> 01:05:24.921 and also the predicted phenotype in those patients. 01:05:25.588 --> 01:05:28.966 So the hemolytic anemia, is 01:05:30.134 --> 01:05:32.136 we talked about the inherited form 01:05:32.136 --> 01:05:35.139 of hemolytic anemia. 01:05:35.139 --> 01:05:39.435 Now a little bit about the acquired form of hemolytic anemia inherited forms. 01:05:39.435 --> 01:05:43.272 Although very interesting, we don't see that commonly acquired 01:05:43.272 --> 01:05:47.693 forms of hemolytic anemia are much more common than the innate 01:05:48.653 --> 01:05:50.863 immune mediated. 01:05:50.863 --> 01:05:53.115 We see commonly 01:05:53.115 --> 01:05:57.286 in cases of infections, micro angioplasty, hemolytic anemia. 01:05:57.286 --> 01:06:01.207 Basically it it's called it leads to red 01:06:01.207 --> 01:06:04.210 blood cell, destruction in 01:06:04.961 --> 01:06:08.965 we see all these destructed red blood cells under the painful sphere. 01:06:09.757 --> 01:06:11.968 It can be associated with infection. 01:06:11.968 --> 01:06:12.635 So again, there's 01:06:12.635 --> 01:06:17.139 a big list of hemolytic anemia acquired forms of hemolytic anemia. 01:06:17.556 --> 01:06:20.101 And these are the common like, forms. 01:06:20.101 --> 01:06:23.104 But again this there is a big list 01:06:23.270 --> 01:06:26.273 of acquired forms. 01:06:26.524 --> 01:06:29.527 Immune mediated hemolytic anemia. 01:06:29.527 --> 01:06:32.446 Most of the time we might not even, 01:06:32.446 --> 01:06:34.699 know the exact etiology. Why? 01:06:34.699 --> 01:06:37.702 There is a hemolytic anemia in this. 01:06:38.703 --> 01:06:42.456 In some of the patients, it basically leads to premature 01:06:42.456 --> 01:06:45.960 destruction of red blood cells due to acquired antibodies. 01:06:46.293 --> 01:06:49.296 And why the patient has particular antibodies. 01:06:49.630 --> 01:06:52.216 It's not it's not always clear. 01:06:52.216 --> 01:06:53.968 It could could be due to some blood 01:06:53.968 --> 01:06:57.638 infection or it could be due to some exposure in the past. 01:06:58.097 --> 01:07:01.058 So these patients basically have acquired antibodies. 01:07:01.058 --> 01:07:04.645 And that leads to the binding of these antibodies 01:07:04.645 --> 01:07:08.149 to the red blood cells and destruction of the red blood cells. 01:07:08.649 --> 01:07:10.234 There are two make test, 01:07:11.193 --> 01:07:14.655 basic test, direct test and indirect test. 01:07:15.031 --> 01:07:18.034 That indirect indirect forms test. 01:07:18.159 --> 01:07:21.162 We are trying to detect the 01:07:21.787 --> 01:07:23.706 the antibodies 01:07:23.706 --> 01:07:26.709 which are attached to the surface of the red blood cells 01:07:27.168 --> 01:07:29.587 in the indirect test, 01:07:29.587 --> 01:07:34.425 basically trying to find the antibodies in the unbound, form 01:07:34.425 --> 01:07:37.386 or not really bound to the red blood cells. 01:07:37.386 --> 01:07:40.890 So these are the basic test which tells us about the, 01:07:41.766 --> 01:07:44.769 whether auto antibodies are present, 01:07:45.352 --> 01:07:48.647 in the, in the patient's circulation or if they are present, 01:07:48.647 --> 01:07:52.693 whether it's in the form of attach, if they are attached to the red blood 01:07:52.693 --> 01:07:55.696 cells or if they are freely circulating in the cell. 01:07:57.114 --> 01:07:57.907 Microalgae. 01:07:57.907 --> 01:07:58.783 Antibiotic hemolytic 01:07:58.783 --> 01:08:02.661 anemia is characterized by red blood cell fragments in the peripheral blood, 01:08:02.870 --> 01:08:07.208 so it is also known as sister sites differential. 01:08:07.249 --> 01:08:10.002 If you're seeing a lot of sister sites under the peripheral blood, 01:08:11.670 --> 01:08:12.963 in the peripheral smear. 01:08:12.963 --> 01:08:13.881 Other differential. 01:08:13.881 --> 01:08:16.884 The most common differential is 01:08:16.926 --> 01:08:19.929 Chombo thrombotic thrombocytopenia purpura. 01:08:19.929 --> 01:08:22.973 This is again a rare although it's a rare condition. 01:08:22.973 --> 01:08:26.936 But it's a really dangerous, condition and is characterized 01:08:26.936 --> 01:08:30.022 by five different parameters like the patient 01:08:30.022 --> 01:08:33.943 also has not only has anemia, the platelets are also involved. 01:08:34.401 --> 01:08:38.114 The patient also has renal problems, neurological problems. 01:08:38.489 --> 01:08:41.450 So there are like 4 or 5 different parameters 01:08:41.450 --> 01:08:44.453 which define thrombotic thrombocytopenia purpura. 01:08:44.495 --> 01:08:47.498 And these patients need to be treated 01:08:48.582 --> 01:08:50.167 as soon as possible. 01:08:50.167 --> 01:08:53.170 Otherwise these patients really succumb to the 01:08:53.796 --> 01:08:56.590 the massive hemolysis going on 01:08:56.590 --> 01:08:57.341 occurs. 01:08:57.341 --> 01:09:01.762 Hemolytic uremic syndrome happens basically due to some of the, toxins, 01:09:02.138 --> 01:09:05.474 some of the bacterial, equally, and Shigella toxins. 01:09:05.975 --> 01:09:10.479 These are also, again, not common, but these these patients need to be treated. 01:09:12.273 --> 01:09:14.191 And then again, the sister sites 01:09:14.191 --> 01:09:17.903 are these red blood cell fragments can form in so many different conditions, 01:09:18.279 --> 01:09:21.824 many carcinomas disseminated intravascular population 01:09:21.824 --> 01:09:25.828 because of the derangement or the Coughlan proteins. 01:09:27.037 --> 01:09:30.082 And some of these rare some of these are rare called 01:09:30.082 --> 01:09:33.335 causes of sister sites malignant hypertension. 01:09:33.335 --> 01:09:38.716 Some of these giant really big hemangioma is hemoglobin hemoglobin, urea 01:09:38.716 --> 01:09:42.511 and drugs are one of the common cause of the 01:09:42.636 --> 01:09:45.639 our sister site formation. 01:09:46.056 --> 01:09:47.266 This is what it looks like. 01:09:47.266 --> 01:09:51.228 The sister sites are the fragmented red blood cell under the pressure smear. 01:09:51.645 --> 01:09:54.607 So these are the normal red blood cells. 01:09:54.982 --> 01:09:57.985 These basically cells are fragmented. 01:10:00.321 --> 01:10:03.324 Like and and your particular anemia. 01:10:04.658 --> 01:10:07.036 This I'm just mentioning this 01:10:07.036 --> 01:10:10.623 because this is the again, this is a rare phenomenon marking globin urea. 01:10:10.998 --> 01:10:13.459 But it's like a very interesting phenomenon. 01:10:13.459 --> 01:10:17.671 It happens basically it's a disorder of transient hemoglobin emission 01:10:17.713 --> 01:10:23.177 or hemoglobin urea due to forceful contact of the body with hard surface. 01:10:23.594 --> 01:10:26.555 So although it's not that rare, 01:10:27.014 --> 01:10:31.060 although it's not that common, it's a very unique phenomena. 01:10:31.602 --> 01:10:37.358 So sometimes it's seen in marching like soldiers or marching band. If, 01:10:38.651 --> 01:10:39.735 when there is a 01:10:39.735 --> 01:10:43.030 contact of the body with the hard surface 01:10:43.530 --> 01:10:46.408 and that leads to no one really understands 01:10:46.408 --> 01:10:49.411 what is the pathophysiology 01:10:49.495 --> 01:10:51.914 in this, hemoglobin 01:10:51.914 --> 01:10:52.539 destruction. 01:10:52.539 --> 01:10:54.250 But this is like a unique phenomenon. 01:10:54.250 --> 01:10:59.505 That's why prolonged marches, competitive running, karate and all those things 01:10:59.922 --> 01:11:03.509 which can lead to, although very rarely. 01:11:05.594 --> 01:11:08.347 Hemolytic anemia associated with infection. 01:11:08.347 --> 01:11:12.559 This is again there's again big list of all different 01:11:12.559 --> 01:11:17.064 kind of infection which can cause hemolytic process 01:11:17.064 --> 01:11:20.067 in the red blood. So. 01:11:22.152 --> 01:11:23.362 Last but not 01:11:23.362 --> 01:11:27.032 the least is the proximal nocturnal hemoglobin urea. 01:11:27.032 --> 01:11:29.952 It is again it's always a rare condition. 01:11:29.952 --> 01:11:32.454 It's again it's a very unique phenomena. 01:11:32.454 --> 01:11:37.001 It's characterized by anemia and dark urine at night. 01:11:37.001 --> 01:11:41.505 So there is a destruction of red blood cells at the at night. 01:11:41.505 --> 01:11:45.551 So that's why the name nocturnal comes from also leads 01:11:45.551 --> 01:11:49.430 to formation of venous thrombosis, especially in the large blood vessels. 01:11:49.972 --> 01:11:51.932 It's a quite clonal disorder. 01:11:51.932 --> 01:11:54.977 So it's not really a hereditary or genetic cause. 01:11:55.227 --> 01:12:00.065 The mutation it's seen in this speculated interferon gamma gene. 01:12:00.065 --> 01:12:01.358 This particular gene 01:12:02.526 --> 01:12:04.236 and this particular mutation 01:12:04.236 --> 01:12:08.866 is associated with the proximal nocturnal hemoglobin area. 01:12:09.533 --> 01:12:12.745 Because of this particular mutation in this gene, the 01:12:12.745 --> 01:12:16.040 the synthesis of the GPI 01:12:16.040 --> 01:12:19.251 linked protein, which is the most important protein, 01:12:19.835 --> 01:12:22.838 to link red blood cell membrane 01:12:23.464 --> 01:12:25.716 if they are effective, the red blood 01:12:25.716 --> 01:12:28.886 cell membrane proteins are kind of not linked properly, 01:12:28.886 --> 01:12:32.473 and they're much more prone to complement mediated lysis. 01:12:33.098 --> 01:12:37.102 The diagnostic workup of this condition is basically a full cytometry 01:12:37.102 --> 01:12:41.023 based test, which looks for the GPI linked proteins. 01:12:41.482 --> 01:12:44.526 Treatment is, basically this particular drug. 01:12:44.526 --> 01:12:49.948 It has been in use for last, I would say 7 or 8 years. Now. 01:12:50.324 --> 01:12:54.870 This is a monoclonal antibody against the C5 which is a complement factor. 01:12:55.287 --> 01:12:56.705 And it works pretty good. 01:12:56.705 --> 01:12:58.707 It's it's a directed therapy. 01:13:00.000 --> 01:13:03.003 Towards the complement C5. 01:13:04.129 --> 01:13:07.633 One of the other important caveat of this particular condition 01:13:07.633 --> 01:13:11.887 is about 10 to 20% of this, PNH 01:13:12.596 --> 01:13:15.015 associated with a plastic anemia. 01:13:15.015 --> 01:13:19.603 So basically bone marrow failure and minor this syndrome, 01:13:19.603 --> 01:13:24.191 which is again, it's kind of a clonal disorder of the bone marrow. 01:13:24.441 --> 01:13:27.444 So any time, if, 01:13:27.528 --> 01:13:31.198 if a patient or clinician is suspecting a PNH, 01:13:31.198 --> 01:13:35.411 they need to look for a plastic name that is because of the close 01:13:36.036 --> 01:13:39.039 correlation between these. 01:13:39.832 --> 01:13:41.208 That's about it. 01:13:41.208 --> 01:13:46.296 That was in basic nutshell, but all these three different types 01:13:46.296 --> 01:13:49.800 of anemia, microscopic anemia, macro anemia, 01:13:50.592 --> 01:13:52.928 and normal city anemia. 01:13:52.928 --> 01:13:58.392 I try to basically, give a basic information about these anemia. 01:13:58.392 --> 01:14:03.188 Again, anemia is a really big lost topic. 01:14:03.188 --> 01:14:05.858 And we can talk about it for like hours. 01:14:05.858 --> 01:14:10.696 But this is like a basic kind of work of, of all, all the anemia combined. 01:14:11.155 --> 01:14:13.532 And I hope, that's helpful. 01:14:13.532 --> 01:14:14.324 Thank you very much.