WEBVTT 00:00:00.000 --> 00:00:03.800 Q I am Miranda Chimchar. 00:00:03.800 --> 00:00:07.733 I'm one of the first year pathology residents, and today 00:00:07.733 --> 00:00:12.866 I'm going to be talking about immune thrombocytopenia, or ITP. 00:00:13.133 --> 00:00:18.000 And I'm going to specifically be using, an interesting, patient 00:00:18.000 --> 00:00:21.000 that we had on service. 00:00:25.600 --> 00:00:26.733 There we go. 00:00:26.733 --> 00:00:30.533 So my objectives, I'm first going to talk about the different types 00:00:30.533 --> 00:00:34.133 of ITP and provide examples of each. 00:00:34.466 --> 00:00:37.466 Then I'm going to talk about the clinical presentation 00:00:37.466 --> 00:00:40.600 and then the treatment options 00:00:41.933 --> 00:00:44.933 and the indications for providing treatment. 00:00:46.266 --> 00:00:49.400 The patient that we saw on service was a 70 year 00:00:49.400 --> 00:00:52.533 old male who presented with ongoing nose bleed. 00:00:53.000 --> 00:00:57.400 He had a history of hypertension, type two diabetes, gout, 00:00:57.400 --> 00:01:02.600 chronic sinusitis and aortic stenosis that had been, repaired 00:01:03.000 --> 00:01:06.000 and he had actually been diagnosed with ITP. 00:01:06.933 --> 00:01:07.400 It kind of 00:01:07.400 --> 00:01:10.933 varied on who you talk to, but about 5 to 10 years ago. 00:01:11.266 --> 00:01:14.533 And so he'd been getting treatment, elsewhere 00:01:14.866 --> 00:01:17.866 with rituximab for his ITP. 00:01:20.000 --> 00:01:21.333 Going into what 00:01:21.333 --> 00:01:24.933 ITP is so immune thrombocytopenia. 00:01:25.200 --> 00:01:28.333 But in the past it's also been called idiopathic 00:01:28.333 --> 00:01:32.866 thrombocytopenia purpura or immune thrombocytopenia purpura. 00:01:32.866 --> 00:01:35.333 So you'll hear those as well, 00:01:35.333 --> 00:01:39.066 which has definitely been been confusing to me in the past. 00:01:39.733 --> 00:01:41.400 And there are three different types. 00:01:41.400 --> 00:01:44.533 The first being primary ITP, 00:01:44.800 --> 00:01:49.333 which has no underlying conditions that are causing the low platelet count. 00:01:50.133 --> 00:01:54.733 And then there's second tier ITP, which is a low platelet count. 00:01:54.733 --> 00:01:57.133 That's caused by another condition. 00:01:57.133 --> 00:02:02.400 And then drug induced which is caused by a drug dependent platelet antibody 00:02:02.666 --> 00:02:07.600 that's lowering the platelet counts and causing common culprits. 00:02:08.266 --> 00:02:13.733 Would be the penicillins cephalosporins, quinine and NSAIDs. 00:02:14.933 --> 00:02:18.333 Looking at the secondary ITP, 00:02:18.733 --> 00:02:24.600 it can be caused by infections such as HIV, said a Megalo virus 00:02:24.600 --> 00:02:28.933 shingles Covid h pylori that cause, 00:02:29.200 --> 00:02:32.533 causes stomach ulcers, hepatitis C 00:02:33.000 --> 00:02:36.266 it can be caused by autoimmune conditions like lupus 00:02:36.600 --> 00:02:39.466 or anti phospholipid syndrome. 00:02:39.466 --> 00:02:43.266 It can be caused by deficiencies like selective IGA 00:02:43.266 --> 00:02:46.866 deficiency or common variable immunodeficiency. 00:02:47.600 --> 00:02:50.600 It can be caused by vaccinations. 00:02:51.200 --> 00:02:54.200 MMR and possibly Covid. 00:02:54.266 --> 00:02:57.333 And then it can be caused by hematopoietic malignancies 00:02:57.333 --> 00:03:00.333 such as CLL. 00:03:00.800 --> 00:03:03.200 Going into the primary ITP, 00:03:03.200 --> 00:03:07.200 which is what my patient had and what I'm going to be focusing on. 00:03:07.666 --> 00:03:09.733 It's an acquired bleeding disorder. 00:03:09.733 --> 00:03:15.866 And it's usually IgG against platelet membrane glycoproteins specifically 00:03:15.866 --> 00:03:20.733 GG to be three A which in this diagram 00:03:21.066 --> 00:03:24.066 you can see is the 00:03:24.133 --> 00:03:29.466 usually binds with fibrinogen to cross link platelets forming the clot. 00:03:30.933 --> 00:03:32.266 And then so those platelets 00:03:32.266 --> 00:03:36.600 that are bound with antibodies get cleared from circulation by the spleen. 00:03:36.866 --> 00:03:41.333 And that leads to the low platelet counts or the thrombocytopenia. 00:03:42.200 --> 00:03:45.800 In the United States, about 8 in 00:03:45.800 --> 00:03:49.200 100,000 children are affected, each year. 00:03:49.200 --> 00:03:52.200 And then, for adults, it's about 12 00:03:52.266 --> 00:03:56.200 per 100,000 at the younger ages. 00:03:56.533 --> 00:03:59.533 Usually it's that secondary ITP, 00:04:00.133 --> 00:04:02.266 which usually goes into remission 00:04:02.266 --> 00:04:05.266 and it's females are greater than males. 00:04:05.466 --> 00:04:09.133 But as we get older it's usually primary ITP. 00:04:09.466 --> 00:04:13.133 And the female and males that are affected are about equal. 00:04:14.000 --> 00:04:17.533 So we see more, elderly people that are affected 00:04:17.533 --> 00:04:20.533 by ITP than younger people. 00:04:22.000 --> 00:04:24.600 The signs and symptoms include. 00:04:24.600 --> 00:04:26.333 The main one is bleeding. 00:04:26.333 --> 00:04:29.200 So you may have PTK or purpura. 00:04:29.200 --> 00:04:33.533 So in this picture the PTC are those pinprick bruising. 00:04:33.866 --> 00:04:37.333 And then the purpura are where those PTK, 00:04:38.466 --> 00:04:41.466 kind of join together until larger bruises 00:04:42.000 --> 00:04:45.000 and then nose bleeds like our patient had. 00:04:45.533 --> 00:04:47.733 And it very rarely, 00:04:47.733 --> 00:04:50.733 can result in severe bleeding, 00:04:51.266 --> 00:04:53.266 to define thrombocytopenia. 00:04:53.266 --> 00:04:57.200 So the definition is less than 100,000, 00:04:57.666 --> 00:05:00.266 platelets per microliter. 00:05:00.266 --> 00:05:02.666 And severe thrombocytopenia is considered 00:05:02.666 --> 00:05:06.133 less than 20,000 per microliter 00:05:07.533 --> 00:05:10.333 about one fifth to one third of patients 00:05:10.333 --> 00:05:13.333 are actually asymptomatic on presentation. 00:05:13.600 --> 00:05:17.200 And it's, an incidental finding on a CBC. 00:05:18.000 --> 00:05:21.333 So they don't have any bleeding or complications at that time. 00:05:23.466 --> 00:05:26.666 For a workup, it's a diagnosis of exclusion. 00:05:27.200 --> 00:05:32.133 So you want to rule out, drug induced and secondary ITP. 00:05:32.466 --> 00:05:35.466 So you want to do a very thorough, 00:05:36.000 --> 00:05:37.933 history and physical. 00:05:37.933 --> 00:05:41.066 You want to make sure that, you know, all of the medications 00:05:41.066 --> 00:05:44.866 that they're taking, to rule out drug induced. 00:05:44.866 --> 00:05:48.400 And then you want to do some other testing to rule out 00:05:48.400 --> 00:05:51.466 other conditions that could be causing the thrombocytopenia. 00:05:51.800 --> 00:05:54.800 So testing would include a CBC, 00:05:54.800 --> 00:05:59.666 peripheral blood smear, cog testing, thyroid function, 00:05:59.666 --> 00:06:03.933 which can be related to ITP, possibly a bone marrow biopsy, 00:06:05.066 --> 00:06:07.466 immunologic studies. 00:06:07.466 --> 00:06:10.666 Luckily for us in this patient, all of this had already been done 00:06:10.666 --> 00:06:15.133 and ruled out since he'd been diagnosed with ITP many years earlier. 00:06:17.200 --> 00:06:20.000 So going back to our patient, he had been admitted 00:06:20.000 --> 00:06:24.466 multiple times over the past month with ongoing, nosebleeds. 00:06:25.266 --> 00:06:28.266 And his platelet counts had remained fairly low. 00:06:28.533 --> 00:06:33.600 So we first saw him on January 31st, but the platelet count at 22, 00:06:33.933 --> 00:06:38.066 he was back on February 3rd with a platelet count of 11. 00:06:39.000 --> 00:06:41.400 The eighth he got a little bit higher, 00:06:41.400 --> 00:06:44.133 came in with a platelet count of 45. 00:06:44.133 --> 00:06:47.333 And then his latest admission on February 15th, 00:06:47.333 --> 00:06:51.200 he was less than six, so his platelets were not detectable. 00:06:51.600 --> 00:06:55.000 He also presented with bacteremia. 00:06:55.666 --> 00:06:59.400 And a creatinine of 2.5. 00:07:00.133 --> 00:07:02.533 And so the bacteremia may have led 00:07:02.533 --> 00:07:05.533 to increased clearance of platelets. 00:07:06.200 --> 00:07:08.733 And those platelets that were left in circulation 00:07:08.733 --> 00:07:13.533 may have had uremic platelet dysfunction due to the elevated creatinine. 00:07:14.600 --> 00:07:16.466 And so, 00:07:16.466 --> 00:07:19.466 kind of a recipe for disaster and bleeding. 00:07:20.200 --> 00:07:24.866 The other interesting thing in the past, he had been typed as o positive, 00:07:25.666 --> 00:07:32.266 and he came in on the 15th and had an antibody, antibody identified. 00:07:32.733 --> 00:07:35.733 And so that was another mystery for us to solve. 00:07:36.200 --> 00:07:39.600 And I'll talk a little bit more about that in a couple slides. 00:07:40.866 --> 00:07:43.600 But next I want to talk about the indications 00:07:43.600 --> 00:07:47.066 for when we want to treat, a patient with ITP 00:07:47.266 --> 00:07:50.266 when we need to admit them, things like that. 00:07:52.066 --> 00:07:54.066 So patients with ITP are 00:07:54.066 --> 00:07:58.533 at an increased risk for bleeding if they're over 60 years old. 00:07:58.533 --> 00:08:01.333 And so this gentleman was in his 70s. 00:08:01.333 --> 00:08:05.800 If they have really low platelet counts of severe thrombocytopenia, 00:08:06.866 --> 00:08:11.733 like a platelet count of less than 10,000 and a history of prior bleeds. 00:08:12.733 --> 00:08:13.800 So if it's happened in 00:08:13.800 --> 00:08:16.800 the past, it's less likely to happen again. 00:08:18.000 --> 00:08:22.333 The bleeding is kind of put into three main categories. 00:08:22.333 --> 00:08:26.733 The first being critical bleeds, which means the patient is hemodynamic 00:08:26.933 --> 00:08:30.266 in stable or may have respiratory compromised. 00:08:30.600 --> 00:08:35.133 And then kind of one step down from that would be considered a severe bleed 00:08:35.533 --> 00:08:38.466 which has a drop in hemoglobin that's at least 00:08:38.466 --> 00:08:41.466 two grams per deciliter. 00:08:41.533 --> 00:08:46.000 But does not have that hemodynamic instability like the critical bleed. 00:08:46.466 --> 00:08:51.533 And then minor bleeds is basically a catchall category for everything else. 00:08:52.200 --> 00:08:55.333 And putting it into this categories helps us decide 00:08:55.333 --> 00:08:58.333 how we need to treat the patient 00:08:58.733 --> 00:09:00.066 for critical bleeds. 00:09:00.066 --> 00:09:02.733 You want to give a platelet transfusion? 00:09:02.733 --> 00:09:05.600 I.V., IgG and glucose, 00:09:05.600 --> 00:09:08.600 cortical sites or steroids? 00:09:08.666 --> 00:09:12.266 This is the only case that you want to give platelets. 00:09:12.866 --> 00:09:17.066 Because the antibodies that are attaching to the patient's own 00:09:17.666 --> 00:09:21.533 platelets can attach to donor platelets as well and clear them. 00:09:22.200 --> 00:09:26.866 And so it's and unless it's very critical, the patient is not stable. 00:09:27.133 --> 00:09:30.466 You're almost just wasting platelets by giving the platelets to them. 00:09:31.600 --> 00:09:34.866 Unless there's a very severe bleed where those platelets are going, right 00:09:34.866 --> 00:09:39.600 to, to the source and helping to stop it instead of being cleared from circulation. 00:09:40.200 --> 00:09:43.200 It's not not worth it to transfuse them. 00:09:44.000 --> 00:09:48.666 The IVIg can raise the platelet count in 1 to 3 days. 00:09:49.000 --> 00:09:51.066 And the mechanism is that it blocks. 00:09:51.066 --> 00:09:54.333 So it's basically giving a bunch of IgG. 00:09:55.000 --> 00:09:59.933 And so that excess IgG blocks the FC receptors on the phagocytic 00:09:59.933 --> 00:10:03.466 cells in the spleen, which prevents the clearance or hopes 00:10:03.466 --> 00:10:06.866 to prevent the clearance of those antibody coated platelets. 00:10:07.400 --> 00:10:10.400 And then the glucocorticoids take a bit longer. 00:10:10.666 --> 00:10:12.600 2 to 14 days. 00:10:12.600 --> 00:10:16.466 And it's thought that they down regulate the macrophage activity, 00:10:16.800 --> 00:10:19.800 so it decreases the phagocytosis of the platelets. 00:10:20.266 --> 00:10:24.866 And it causes apoptosis in the autoantibody producing lymphocytes. 00:10:24.866 --> 00:10:28.133 So there's less antibodies to coat the platelets as well. 00:10:29.133 --> 00:10:31.000 And so sometimes both are used. 00:10:31.000 --> 00:10:34.933 It kind of depends on the situation and how quickly 00:10:35.266 --> 00:10:38.266 you need to increase the platelet level. 00:10:38.400 --> 00:10:41.600 Kind of how critical the patient is, how much they're bleeding 00:10:42.266 --> 00:10:43.466 for severe bleeds. 00:10:43.466 --> 00:10:47.200 You won't give a platelet transfusion, but you will do the IVIg 00:10:47.200 --> 00:10:49.866 and glucocorticoids, 00:10:49.866 --> 00:10:51.933 for minor bleeds often 00:10:51.933 --> 00:10:54.933 you'll still do IVIg, glucocorticoids. 00:10:55.333 --> 00:10:56.800 But you kind of have a little more time 00:10:56.800 --> 00:11:00.666 you can address if there are other conditions, things like that. 00:11:01.000 --> 00:11:06.066 And then for asymptomatic, if they're less than 20,000, 00:11:06.066 --> 00:11:09.733 you do want to treat them because they're at a higher risk for developing a bleed. 00:11:10.400 --> 00:11:13.400 But if they're greater than 30,000, 00:11:13.666 --> 00:11:16.666 then you don't need to treat them. 00:11:17.733 --> 00:11:20.466 These are the second line treatments. 00:11:20.466 --> 00:11:23.400 So one is a laparoscopic splenectomy. 00:11:23.400 --> 00:11:25.266 This is a permanent treatment. 00:11:25.266 --> 00:11:29.200 You're taking out the organ that's clearing the platelets from circulation. 00:11:30.600 --> 00:11:32.066 And it 00:11:32.066 --> 00:11:35.266 provides a risk to the patient of them being susceptible 00:11:35.266 --> 00:11:39.533 to encapsulated organisms that would normally be cleared by the spleen. 00:11:40.133 --> 00:11:42.533 And so there's, some extra vaccines 00:11:42.533 --> 00:11:45.533 and such that these patients should get to help them. 00:11:46.000 --> 00:11:48.466 Be protected from these infections. 00:11:48.466 --> 00:11:53.600 And because this is a permanent thing, you should wait one year 00:11:53.600 --> 00:11:57.933 after diagnosis, just in case spontaneous remission occurs. 00:11:58.200 --> 00:12:01.666 So you don't want to have the patient undergo this, 00:12:03.200 --> 00:12:05.666 life changing, extensive surgery? 00:12:05.666 --> 00:12:08.666 If potentially the ITP would go away with time. 00:12:09.733 --> 00:12:12.666 You can also give, 00:12:12.666 --> 00:12:17.066 some Mab which our patient had been on, which is less effective 00:12:17.066 --> 00:12:22.466 than the splenectomy, and usually provides shorter periods of remission. 00:12:22.800 --> 00:12:26.266 And of course, like with any medication, there are toxicities and side 00:12:26.266 --> 00:12:28.000 effects associated with it. 00:12:29.866 --> 00:12:30.266 You can 00:12:30.266 --> 00:12:33.666 also give a thrombin point and receptor agonist. 00:12:34.333 --> 00:12:37.533 So thrombus stimulates platelet production. 00:12:38.000 --> 00:12:41.000 So this does not remove the antibody. 00:12:41.066 --> 00:12:44.066 That's binding and causing clearance of the platelets. 00:12:44.066 --> 00:12:48.000 It just increases the platelet production trying to put more platelets 00:12:48.000 --> 00:12:49.800 into circulation. 00:12:49.800 --> 00:12:53.066 And so it's something that you have to continue giving over time. 00:12:53.733 --> 00:12:56.266 Because as soon as you stop it, 00:12:56.266 --> 00:12:59.266 the platelet level can drop again. 00:12:59.666 --> 00:13:03.666 And then you can also give antibody immunoglobulin. 00:13:04.200 --> 00:13:08.200 So this would be like rhodium or other medications similar to that. 00:13:08.866 --> 00:13:12.600 And basically so you can only give this in a pause 00:13:12.600 --> 00:13:16.333 and not excuse me in d positive patients. 00:13:17.066 --> 00:13:21.600 And so the immunoglobulin will bind to their red blood cells. 00:13:21.933 --> 00:13:24.866 And the idea is that it will keep the spleen, 00:13:25.800 --> 00:13:27.866 kind of engaged clearing 00:13:27.866 --> 00:13:31.466 that antibody instead of the platelets with bound antibody. 00:13:31.800 --> 00:13:35.733 And so it's kind of hoping to to distract the spleen, keep it busy 00:13:36.000 --> 00:13:39.000 in order to keep more platelets in circulation. 00:13:39.533 --> 00:13:42.933 And so if you think about it, for pregnant women 00:13:42.933 --> 00:13:46.333 at 28 weeks that are o-negative with, 00:13:46.733 --> 00:13:51.533 or not just negative D negative with a D positive baby, 00:13:51.800 --> 00:13:54.666 they get one vial of rhodium 00:13:54.666 --> 00:13:59.133 in these patients if they have a, hemoglobin 00:13:59.133 --> 00:14:04.400 of greater than ten you give 50 micrograms per kilogram. 00:14:05.066 --> 00:14:08.400 So in this patient it would have been over 20 vials. 00:14:09.533 --> 00:14:12.000 And if their hemoglobin is 8 00:14:12.000 --> 00:14:15.000 to 10g per deciliter for hemoglobin, 00:14:15.733 --> 00:14:18.866 you give 24 to 40g per deciliter. 00:14:19.600 --> 00:14:21.600 So that would be about half that. 00:14:21.600 --> 00:14:25.266 So our patient actually at an outside hospital hospital 00:14:25.666 --> 00:14:29.066 got ten vials of rhodium. 00:14:30.266 --> 00:14:33.266 And so that's why he had the antibody 00:14:33.333 --> 00:14:36.333 on his type in screen. 00:14:37.000 --> 00:14:38.000 So our patient now, 00:14:38.000 --> 00:14:41.000 he actually underwent splenic splenectomy. 00:14:41.600 --> 00:14:47.066 And I will kind of add about splenectomy that a lot of times people are nervous 00:14:47.066 --> 00:14:50.600 about doing that in these patients because their platelets are so low. 00:14:51.333 --> 00:14:57.733 But with if you do it with a laparoscopy, so that's where you kind of put ports in. 00:14:57.733 --> 00:15:00.333 You don't have to open the entire abdomen. 00:15:00.333 --> 00:15:03.866 The bleeding can be pretty minimal and safe for these patients. 00:15:04.533 --> 00:15:09.533 And so we are able to do that and afterwards his platelet count 00:15:09.533 --> 00:15:15.133 was 25, and stable, staying there where he'd been less than six prior. 00:15:15.533 --> 00:15:19.133 He did have a little bit of minor bruising, not bruising. 00:15:19.133 --> 00:15:19.466 Excuse me? 00:15:19.466 --> 00:15:22.933 Minor oozing, and bleeding at the incision sites. 00:15:23.533 --> 00:15:28.600 But they were able to apply some topical Amilcar, and stop that. 00:15:28.600 --> 00:15:30.200 So he did really well. 00:15:30.200 --> 00:15:34.133 And then it was just continuing to monitor for hemolysis 00:15:34.400 --> 00:15:39.533 since he had been given the antibody and he was, oh, positive. 00:15:39.533 --> 00:15:44.333 So it does run the risk of, of causing hemolysis in his own red blood cells. 00:15:44.666 --> 00:15:47.600 But so far he hadn't had any hemolysis. 00:15:47.600 --> 00:15:49.400 And he was stable. 00:15:49.400 --> 00:15:54.133 So definitely a very interesting case that kind of took us through the whole, 00:15:55.466 --> 00:15:58.466 whole treatment options for ITP. 00:15:59.800 --> 00:16:01.200 These were my sources.