WEBVTT 00:00:08.733 --> 00:00:11.600 All right, so hi everyone. 00:00:11.600 --> 00:00:13.800 I'm Taylor Jackson, 00:00:13.800 --> 00:00:17.000 the or case reviewer of the day. 00:00:18.600 --> 00:00:20.800 So let's jump right in. 00:00:20.800 --> 00:00:22.533 Here's some quick objectives. 00:00:22.533 --> 00:00:25.533 Kind of where we're heading for today. 00:00:25.533 --> 00:00:28.533 So today I'd like to start out just going over. 00:00:29.400 --> 00:00:34.266 This case we've had recently interesting, sort of scenario. 00:00:34.266 --> 00:00:38.200 Still kind of thinking about it a little bit, but, let's break it down. 00:00:39.400 --> 00:00:42.400 So this is, 86 year old fellow. 00:00:42.600 --> 00:00:45.466 Oh. Pause. And he's had, 00:00:45.466 --> 00:00:48.466 pretty long standing history of anemia. 00:00:48.733 --> 00:00:51.733 Greater than ten years. 00:00:52.333 --> 00:00:55.333 And he's been doing okay 00:00:55.800 --> 00:00:59.333 for most of that time, according to the notes that we have on him. 00:00:59.333 --> 00:01:01.000 Anyway. 00:01:01.000 --> 00:01:04.000 Until about March of 2020. 00:01:04.266 --> 00:01:07.933 Bad time to for things to be going 00:01:07.933 --> 00:01:10.933 downhill. But, 00:01:11.466 --> 00:01:15.000 so he started noticing he had a lot of fatigue. 00:01:15.266 --> 00:01:18.733 He had noticed this kind of 15 pound weight loss and also his, 00:01:19.333 --> 00:01:22.333 exercise tolerance was way down from his baseline. 00:01:22.666 --> 00:01:26.600 So he went in, to see his physician found to be pants. 00:01:26.600 --> 00:01:28.200 Height of panic. 00:01:28.200 --> 00:01:29.466 You know, everything down. 00:01:29.466 --> 00:01:33.133 Not huge numbers, but, you know, still down across the board. 00:01:33.933 --> 00:01:36.466 So at the time, they did a bone marrow biopsy 00:01:36.466 --> 00:01:39.533 and they it wasn't quite normal. 00:01:39.600 --> 00:01:41.466 It was a little bit hyper cellular. 00:01:41.466 --> 00:01:44.400 I believe in the note they, they referenced about 50%. 00:01:44.400 --> 00:01:46.933 So still high for his age. 00:01:48.000 --> 00:01:48.866 And they saw 00:01:48.866 --> 00:01:52.066 kind of this roid megalo blast void maturation 00:01:52.066 --> 00:01:55.533 and some abnormal cytogenetics but nothing really definitive. 00:01:56.400 --> 00:01:59.800 And that's kind of where they went with it. 00:01:59.800 --> 00:02:03.266 They they couldn't really put a good name on it, 00:02:03.266 --> 00:02:07.400 but diagnosed it as just, low grade myelodysplastic syndrome. 00:02:07.400 --> 00:02:10.400 Kind of left it with that. 00:02:10.933 --> 00:02:13.933 So about a year after that, 00:02:14.666 --> 00:02:17.666 he presented again with severe anemia. 00:02:18.400 --> 00:02:21.600 And looked like he was hemolysis as well. 00:02:22.400 --> 00:02:25.533 So over the course of that year, he had been on chemotherapy. 00:02:25.533 --> 00:02:27.666 They decided to hold that. 00:02:27.666 --> 00:02:30.000 Because of the anemia and hemolysis. 00:02:30.000 --> 00:02:33.066 And they started him on prednisone to try to mitigate 00:02:33.066 --> 00:02:36.066 that. 00:02:36.066 --> 00:02:39.066 Kind of following him as they tried. 00:02:39.200 --> 00:02:41.200 Started to try to taper em off the steroid. 00:02:41.200 --> 00:02:43.466 They were having real difficult time doing that. 00:02:43.466 --> 00:02:46.866 Wasn't, you know, couldn't really get down. 00:02:47.800 --> 00:02:50.600 On that. So they started in minor tucks. 00:02:50.600 --> 00:02:55.800 Mab still having this anemia with hemolysis pick picture 00:02:56.400 --> 00:03:00.200 and started him on rituximab in February of this year. 00:03:02.133 --> 00:03:06.200 And so they wanted to see what was going on. 00:03:07.133 --> 00:03:09.800 As far as from his, bone marrow, 00:03:09.800 --> 00:03:12.466 they're biopsied him. 00:03:12.466 --> 00:03:14.866 And at this point, 00:03:14.866 --> 00:03:17.733 it actually came back looking pretty good. 00:03:17.733 --> 00:03:21.400 You can see they said in the note 00:03:21.400 --> 00:03:25.466 that it did not meet the criteria for MDS anymore, these abnormal findings 00:03:25.466 --> 00:03:29.800 that they had initially seen, year prior had resolved. 00:03:30.333 --> 00:03:33.333 So he had responded to the chemotherapy, 00:03:34.200 --> 00:03:37.800 but he had this ongoing kind of the anemia and hemolysis picture. 00:03:38.466 --> 00:03:42.800 They did a, CT abdomen on him in December down. 00:03:43.200 --> 00:03:46.266 He had a big spleen and just kind of 00:03:46.266 --> 00:03:49.266 this same, same presentation. 00:03:49.400 --> 00:03:52.200 Continued with the anemia. 00:03:52.200 --> 00:03:54.400 Overall, he per the. No. 00:03:54.400 --> 00:03:57.400 He seemed to be doing okay, tolerating, 00:03:57.866 --> 00:04:00.466 his therapy fairly well. 00:04:00.466 --> 00:04:03.466 Still able to do his activities of daily living. 00:04:04.000 --> 00:04:08.666 But, you know, from a lab perspective, just kind of had this ongoing thing. 00:04:10.600 --> 00:04:12.800 So we decided to do 00:04:12.800 --> 00:04:16.600 a bunch of labs or his, hematology team did anyway. 00:04:16.866 --> 00:04:19.466 This was back in November. 00:04:19.466 --> 00:04:22.466 And this is where, you know, when I'm talking about, 00:04:23.000 --> 00:04:26.200 evidence of hemolysis, we're looking at some particular labs. 00:04:26.200 --> 00:04:31.266 They're big ones for that is, the total bilirubin, the have two globin in the LDH. 00:04:31.800 --> 00:04:34.466 And then we also evaluate the reticular sites to see 00:04:34.466 --> 00:04:37.800 if you know, is anemic, has a marrow problem 00:04:37.800 --> 00:04:41.466 or is the marrow working and they're being destroyed elsewhere. 00:04:42.133 --> 00:04:45.666 So as you can see his total bilirubin was elevated 00:04:45.866 --> 00:04:49.466 and his have to globin was below our limit of detection. 00:04:50.733 --> 00:04:53.666 And it's been that way, you know, going back in the chart 00:04:53.666 --> 00:04:59.000 for months and months, couldn't find any level, above ten. 00:05:00.133 --> 00:05:02.066 Up to today, even. 00:05:02.066 --> 00:05:06.800 And then his LDH was persistently high, kind of in this high. 00:05:07.933 --> 00:05:11.733 You know, 1900, over to 2000 range. 00:05:12.600 --> 00:05:15.600 Most recent labs, it was still elevated. 00:05:15.733 --> 00:05:19.200 And so he's still got kind of this hemolysis picture going on. 00:05:19.400 --> 00:05:21.666 When we looked at his reticular sites. 00:05:21.666 --> 00:05:24.266 They were persistently elevated as well. 00:05:24.266 --> 00:05:26.466 So you can see our range here. 00:05:26.466 --> 00:05:28.800 It's about 1 to 2.6%. 00:05:28.800 --> 00:05:33.466 And he was consistently above that, getting as high as 6.5. 00:05:34.400 --> 00:05:37.200 In the last couple months. 00:05:37.200 --> 00:05:39.600 The other thing they noted, on 00:05:39.600 --> 00:05:43.666 his smear is that there were nucleated reds present. 00:05:44.000 --> 00:05:46.000 Not a whole lot. 00:05:46.000 --> 00:05:48.866 The kind of, 00:05:48.866 --> 00:05:52.066 reference range on this is, 0.1, 00:05:52.533 --> 00:05:56.533 and he was getting, you know, numbers in like 0.2, 0.3. 00:05:56.533 --> 00:06:00.200 So not a ton of, nucleated reds present, but 00:06:01.333 --> 00:06:04.333 a little more than you'd expect. 00:06:05.333 --> 00:06:08.333 So to work him up, try to figure out what was going on. 00:06:09.066 --> 00:06:10.733 We sent off for a super dat, 00:06:12.600 --> 00:06:14.066 because he was getting this week 00:06:14.066 --> 00:06:18.200 positive on IgG and a moderate positive on C3. 00:06:18.866 --> 00:06:22.400 So as part of this super Dat, they also did a, 00:06:23.400 --> 00:06:26.400 called, Liss wash 00:06:26.600 --> 00:06:28.800 which I'll talk about a little more 00:06:28.800 --> 00:06:31.800 remained week positive on that. 00:06:32.533 --> 00:06:35.466 And then they also ran, 00:06:35.466 --> 00:06:39.000 his sample with Anti-Gmo and IGA. 00:06:39.000 --> 00:06:40.666 Both of those came back negative. 00:06:40.666 --> 00:06:43.333 Talk a little bit more about that as well. 00:06:43.333 --> 00:06:47.466 Continuing to try to figure out what was causing the hemolysis. 00:06:47.466 --> 00:06:51.600 We did, Donna Lynch Steiner test, and she came back negative. 00:06:52.333 --> 00:06:55.400 This is, normally a test we do when we're thinking about, 00:06:55.600 --> 00:06:58.466 paroxysmal cold hemoglobin. Urea. 00:06:58.466 --> 00:07:03.200 There's association with an anti antibody with this came back negative. 00:07:03.200 --> 00:07:07.266 So less likely it's, pKa for that. 00:07:08.800 --> 00:07:11.333 And then just to rule it out we did it. 00:07:11.333 --> 00:07:13.800 Attempts 13 came back 00:07:15.000 --> 00:07:17.533 within the reference interval. 00:07:17.533 --> 00:07:20.533 So unlikely that it was TTP there. 00:07:22.533 --> 00:07:25.266 And so just kind of continuing to see 00:07:25.266 --> 00:07:28.400 if there was some other hematological and lignin see going on. 00:07:28.400 --> 00:07:30.066 They ordered, 00:07:30.066 --> 00:07:33.866 immuno fixation electrophoresis, which also came back normal. 00:07:34.400 --> 00:07:35.533 No, no. 00:07:35.533 --> 00:07:38.533 Spikes or monoclonal proteins identified there. 00:07:38.866 --> 00:07:43.200 So all in all, really all we're seeing is labs that, 00:07:43.466 --> 00:07:46.333 you know, point to this ongoing hemolysis. 00:07:46.333 --> 00:07:48.866 Marrow is still producing. 00:07:48.866 --> 00:07:51.866 You can see it's pushing out cells. 00:07:51.866 --> 00:07:55.200 And then there's just this this week positivity on the Dat. 00:07:56.466 --> 00:08:00.600 But you know, not not super specific 00:08:00.600 --> 00:08:03.600 as to what exactly is going on there. 00:08:05.133 --> 00:08:08.133 So continuing on, 00:08:09.533 --> 00:08:11.866 up to today, he still has, 00:08:11.866 --> 00:08:14.200 evidence of hemolysis on his labs. 00:08:14.200 --> 00:08:18.000 He remains inside a Pinnick the most recent bone 00:08:18.000 --> 00:08:21.266 marrow biopsy, which was done just a week or two ago. 00:08:21.933 --> 00:08:26.600 Totally normal cellular marrow, not MDS anymore. 00:08:27.266 --> 00:08:32.933 And, on the smear review, just kind of reiterating what we saw with the labs. 00:08:32.933 --> 00:08:33.466 He's got, 00:08:34.666 --> 00:08:37.666 this macro acidic anemia and, 00:08:37.733 --> 00:08:40.733 limp flow apnea and thrombocytopenia. 00:08:41.866 --> 00:08:44.933 I just wanted to add in, on the smear review. 00:08:44.933 --> 00:08:48.400 One of the comments, seemed pertinent here was that, 00:08:49.600 --> 00:08:52.200 in this case, anemia with thrombocytopenia, 00:08:52.200 --> 00:08:55.200 the decreased hap globin increase, LDH. 00:08:55.533 --> 00:08:58.533 They also saw some rare Spiro sites, 00:08:58.733 --> 00:09:01.733 to them, indicated an immune mediated process. 00:09:02.533 --> 00:09:03.666 It's understandable. 00:09:03.666 --> 00:09:07.200 We we've seen, evidence of that with the D8, 00:09:07.933 --> 00:09:10.933 which they recommended in their note. 00:09:11.333 --> 00:09:14.000 And then kind of what stuck out to me 00:09:14.000 --> 00:09:17.866 also was, macro acidic anemia without make a little blast IC changes 00:09:18.466 --> 00:09:21.600 may be associated with the patient's underlying MDS. 00:09:22.266 --> 00:09:25.200 Although we you know, they on the biopsy 00:09:25.200 --> 00:09:28.200 they said didn't really meet criteria for that anymore. 00:09:28.733 --> 00:09:31.666 But you can also see this presentation with liver disease 00:09:31.666 --> 00:09:35.400 hypothyroidism alcohol use drug effects. 00:09:35.733 --> 00:09:40.466 And then they mentioned evaluating for a B12 or folate deficiency as well. 00:09:42.866 --> 00:09:45.666 So I'll get into that a little more. 00:09:45.666 --> 00:09:48.666 So this is kind of where we're at with him. 00:09:48.733 --> 00:09:52.200 Haven't really found a good identification 00:09:52.733 --> 00:09:56.400 yet on what's causing this hemolysis. 00:09:58.933 --> 00:10:00.666 So I wanted to talk a little bit 00:10:00.666 --> 00:10:04.800 about some of the various causes of, hemolysis. 00:10:04.800 --> 00:10:11.666 So we think about and then, continue on, you know, even earlier in the process, 00:10:11.666 --> 00:10:14.800 if there's a case for, intermediary hemolysis. 00:10:14.800 --> 00:10:17.733 So you can see there's a whole bunch of non 00:10:17.733 --> 00:10:21.600 immune causes that can cause hemolysis, kind of top of list. 00:10:21.600 --> 00:10:24.600 These enzyme deficiencies like D6, PD, 00:10:25.466 --> 00:10:28.533 pyruvate kinase deficiency, which I spoke about last week. 00:10:29.000 --> 00:10:32.533 And then hemoglobin OP these liver disease infection 00:10:33.600 --> 00:10:35.800 infectious agents for example 00:10:35.800 --> 00:10:38.800 like Bartonella but Baeza malaria 00:10:39.000 --> 00:10:40.933 and then mechanical destruction if they've got 00:10:43.000 --> 00:10:45.333 stenosis in one of their 00:10:45.333 --> 00:10:49.666 heart valves that can lead to some destruction or, 00:10:51.266 --> 00:10:54.266 if they've got a replacement valve and then the, 00:10:54.800 --> 00:10:58.200 the, the mahase or the my trans you Pathak hemolytic anemia. 00:10:58.266 --> 00:11:01.933 So we think of like TTP or h u s and dic. 00:11:02.600 --> 00:11:05.333 Things that have caused damage to these blood vessels that start 00:11:05.333 --> 00:11:09.400 all these, micro clots, which, cause shear to the red cells 00:11:10.400 --> 00:11:13.400 and then some of the immune mediated, 00:11:14.000 --> 00:11:15.933 things that cause hemolysis. 00:11:15.933 --> 00:11:20.800 We think about the autoimmune hemolytic anemia as there's different types. 00:11:21.000 --> 00:11:24.733 Warm I h was called drug induced. 00:11:25.800 --> 00:11:29.733 And then the other things that can cause it is, you know, transfusion reactions 00:11:29.733 --> 00:11:33.600 if you transfuse Abo incompatible, hopefully that's not happening. 00:11:33.600 --> 00:11:35.933 We work really hard to make sure it doesn't. 00:11:35.933 --> 00:11:39.866 And then, this proximal nocturnal hemoglobin area. 00:11:42.600 --> 00:11:44.933 So I wanted to, 00:11:44.933 --> 00:11:47.533 kind of focus in on the term autoimmune hemolytic 00:11:47.533 --> 00:11:51.933 anemia and talk about, some of the findings we see there. 00:11:51.933 --> 00:11:54.933 So we expect to see, positive Dat 00:11:55.000 --> 00:11:58.066 either with IgG or C3 can be both. 00:11:58.866 --> 00:12:03.333 And often we can identify these just at the saline step, you know, 00:12:03.866 --> 00:12:06.866 typically pick up about 60% of these. 00:12:07.200 --> 00:12:12.000 And then when we treat with Peg, we can pick up greater than 90% of those. 00:12:12.000 --> 00:12:15.800 So most of the time, if they, patient has one of these going 00:12:15.800 --> 00:12:18.800 on, we're pretty good at finding those. 00:12:19.933 --> 00:12:21.733 Just from the technical manual, 00:12:21.733 --> 00:12:24.933 they said about a third of the patients show agglutination at room temp, 00:12:25.333 --> 00:12:29.800 but negative at 30 or 37 degrees, which means not clinically significant, 00:12:30.333 --> 00:12:33.466 but something, to be to be aware of. 00:12:34.533 --> 00:12:35.400 Most of the time 00:12:35.400 --> 00:12:38.400 these are caused by IgG antibodies. 00:12:38.400 --> 00:12:41.400 That's why we use, IgG in the test. 00:12:42.600 --> 00:12:45.133 And this is what's been FDA approved. 00:12:45.133 --> 00:12:48.600 Rarely they can be caused by IEM, a gluten NS. 00:12:49.600 --> 00:12:53.733 And that was if you recall, part of the super Dat. 00:12:53.933 --> 00:12:58.933 We, we ran the we ran it using an anti GM and IGA 00:12:59.400 --> 00:13:02.400 to evaluate for this. 00:13:03.200 --> 00:13:04.200 In this case 00:13:04.200 --> 00:13:07.800 maybe not as likely it did come back negative. 00:13:07.800 --> 00:13:12.000 But also when these have been seen in the literature typically causes 00:13:12.000 --> 00:13:15.000 a pretty severe hemolysis. 00:13:16.466 --> 00:13:18.466 So I wanted to talk a little bit 00:13:18.466 --> 00:13:21.600 about dat negative, hemolytic anemia 00:13:22.866 --> 00:13:27.200 and some of the, the reasons you can have a Dat negative, 00:13:27.933 --> 00:13:30.933 autoimmune hemolytic anemia. 00:13:31.266 --> 00:13:34.133 Most commonly it's because 00:13:34.133 --> 00:13:37.266 our detection threshold just isn't quite low enough to catch it. 00:13:37.666 --> 00:13:41.066 So if there's this low level IgG that's causing it, 00:13:41.066 --> 00:13:42.866 but we're not picking it up on the test. 00:13:44.266 --> 00:13:45.266 Other causes as 00:13:45.266 --> 00:13:48.266 I mentioned, is if it's a GM or IGA mediated 00:13:49.200 --> 00:13:51.200 and you need need to run the test 00:13:51.200 --> 00:13:54.200 using those reagents to evaluate for that. 00:13:55.000 --> 00:13:58.000 And then these low affinity ECGs where, 00:13:59.066 --> 00:14:02.466 they, they will bind, but don't stick on very well. 00:14:02.466 --> 00:14:05.466 So by the time we run the regular dat, 00:14:05.466 --> 00:14:07.933 they, they've, dissociated again. 00:14:07.933 --> 00:14:11.266 So part of the one of the ways we can evaluate for this is, 00:14:11.733 --> 00:14:14.733 doing a cold wash with lis, 00:14:15.000 --> 00:14:16.666 kind of 00:14:16.666 --> 00:14:18.800 keeps these, low affinity 00:14:18.800 --> 00:14:22.400 FGS bound on longer so we can, potentially detect them. 00:14:22.400 --> 00:14:27.266 And, we did, do that in on this patient. 00:14:28.733 --> 00:14:32.066 And just to note that this is kind of a non-routine thing. 00:14:33.333 --> 00:14:36.066 So the, 00:14:36.066 --> 00:14:40.200 if your institution does do this, it kind of has to be, 00:14:41.133 --> 00:14:42.266 taken with a grain of salt. 00:14:42.266 --> 00:14:47.266 And, it's there has some variability between institutions. 00:14:48.600 --> 00:14:51.400 So, just something to keep in mind 00:14:51.400 --> 00:14:54.400 in these cases where we are performing these tests. 00:14:57.800 --> 00:14:59.000 And then other causes 00:14:59.000 --> 00:15:03.933 that can maybe, lead to anemia and, hemolysis is, 00:15:04.333 --> 00:15:09.533 this intermediary hemolysis, which I, I did some looking through the literature. 00:15:09.533 --> 00:15:13.133 There's not a whole lot out there about it, but here's some of the ideas. 00:15:13.133 --> 00:15:13.800 They think about it. 00:15:13.800 --> 00:15:15.600 So this is when, you know, the 00:15:15.600 --> 00:15:19.733 antibodies are getting to the red cells while they're still in the marrow. 00:15:19.733 --> 00:15:22.733 Before they really had a chance to get out 00:15:23.400 --> 00:15:26.400 into circulation. 00:15:26.733 --> 00:15:28.800 Per the, the, the, 00:15:28.800 --> 00:15:33.000 the comment from empath, they mentioned, folate and B12 00:15:33.000 --> 00:15:37.333 deficiencies as a potential cause, especially in macro acidic anemia, as 00:15:39.066 --> 00:15:41.066 and this is due to, 00:15:41.066 --> 00:15:47.066 vitamin B12 necessary as part of the, maturation of the red cells. 00:15:47.066 --> 00:15:50.266 So when it's absent, you get derangement of that maturation, 00:15:50.600 --> 00:15:54.400 and that can cause destruction of the red cells even pretty early on, 00:15:55.800 --> 00:15:58.933 and which can lead to this kind of early hemolysis picture. 00:16:00.266 --> 00:16:04.733 Also in the literature, they talked about certain, red 00:16:04.733 --> 00:16:09.266 cell antigens at present early the example they used was antique. 00:16:10.266 --> 00:16:13.466 This is one of the reasons, anti-big K can cause, 00:16:14.600 --> 00:16:17.066 hfmd is that, 00:16:17.066 --> 00:16:20.066 you know, mom's antibodies get in there and start destroying 00:16:20.066 --> 00:16:23.066 baby's red cells while it's still in the marrow. 00:16:24.666 --> 00:16:27.666 So classically, we would evaluate, 00:16:27.733 --> 00:16:30.000 this, in 00:16:30.000 --> 00:16:34.533 pregnant women by doing a amniotic fluid Billy Rubin test and, 00:16:34.800 --> 00:16:38.866 looking at a reticular site count, both of which would be lower 00:16:38.866 --> 00:16:43.866 than other causes of, hif n because you're essentially 00:16:44.266 --> 00:16:49.133 killing those early precursors for the baby's red cells and causing a, 00:16:50.733 --> 00:16:53.733 suppressed or rather, a weakness. 00:16:54.600 --> 00:16:55.666 And then I also found 00:16:55.666 --> 00:16:58.666 in the literature, rarely you can get this, 00:16:59.200 --> 00:17:01.200 caused by a congenital erythropoietin. 00:17:01.200 --> 00:17:02.666 Porphyria. 00:17:02.666 --> 00:17:04.533 It's also known as Gunther disease. 00:17:04.533 --> 00:17:08.600 This is typically seen, like, really early on in life, just after birth 00:17:08.600 --> 00:17:09.533 or early childhood. 00:17:09.533 --> 00:17:12.600 But they did make note that mild forms can, 00:17:13.800 --> 00:17:17.266 not present until late adulthood, like even into the seventh decade. 00:17:18.333 --> 00:17:19.400 Just real briefly. 00:17:19.400 --> 00:17:22.400 This is caused by a defect in neuro porphyrin 00:17:22.533 --> 00:17:25.533 Gen three synthase. 00:17:25.800 --> 00:17:28.800 And that causes buildup of this year or for antigen one, 00:17:29.266 --> 00:17:33.866 normally there's skin find the more common cutaneous findings 00:17:33.866 --> 00:17:37.933 that go along with, periphery is, the blistering. But, 00:17:39.200 --> 00:17:41.600 it can also cause, intermediary 00:17:41.600 --> 00:17:44.600 hemolysis at the same time. 00:17:45.000 --> 00:17:48.000 But there's not a lot of, 00:17:48.533 --> 00:17:52.133 not a lot of information on this, especially in older adults. 00:17:52.933 --> 00:17:55.800 So it's hard to say if that's what's going on in this case. 00:17:57.800 --> 00:18:00.800 Just to wrap up real quickly, 00:18:01.266 --> 00:18:04.666 currently the patient is just receiving supportive treatment or, 00:18:05.333 --> 00:18:08.533 you know, transfusing him, regularly. 00:18:09.000 --> 00:18:11.866 He was starting to become little symptomatic when he was dropping 00:18:11.866 --> 00:18:12.466 below nine. 00:18:12.466 --> 00:18:15.466 So hematology resistance, 00:18:16.133 --> 00:18:18.933 changed his hemoglobin goal to greater than nine. 00:18:18.933 --> 00:18:23.866 And he continues to receive rituximab and prednisone to try to mediate 00:18:24.400 --> 00:18:27.666 what kind of looks like this autoimmune hemolytic anemia picture. 00:18:28.333 --> 00:18:31.200 And so that's kind of what we're doing with him right now. 00:18:31.200 --> 00:18:35.000 We're still trying to think about it, see if there's, some other avenues 00:18:35.000 --> 00:18:38.133 to go to better identify what's causing this.