Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast Narrator - ? 00:11 is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk episode 80. I'm your co host, Dr. Kane. I'm Dr. Schuman, and now I'm Dr. Patel, and the title of today's episode is hit me with your best shot, a brief review of heparin induced thrombocytopenia or HIT and really, to kick this one off, I think it's appropriate to start with a patient case. So we'll have this example, patient who's a 75 year old female who is admitted with peritonitis and found to have a small bowel perforation, and she underwent a repair of that perforation. So on post operative day one, things were looking good. So they started some sub q heparin on her 5000 units, subcutaneous TID for VTE prophylaxis. And over the next several days, with the help of her surgery and IV antibiotics, she was doing great. And then on post operative day seven, she's almost ready to leave the hospital and her CBC, they note that her platelet count decreased from 170,000 to 80,000 over the course of about a day. In addition to that, they noted that she had new left lower extremity swelling and pain, and a diagnostic workup suggested that that was a new DVT for her. So in this context, we have a patient with a platelet trend that is suggestive of thrombocytopenia. For sure, the timing of that platelet decline is very rapid. She has a new thrombus, and she has no other clear causes of a new onset of thrombocytopenia, especially given her clinical improvement, how late in the course we are, as opposed to if this platelet decline happened when she first walked into the hospital, there's a lot of factors there that would put us at clinical suspicion, a high clinical suspicion, of heparin induced thrombocytopenia. So we're going to talk mostly about heparin induced thrombocytopenia in terms of how you know it's not that, because this is a very rare case, but this is a typical case that you may see in clinical practice, right? Speaker 1 02:20 So I think the first question again is, is hit? It's kind of like one of those the white whale, or one of those rare things that you think about, that you talk about it, but as far as what it really, you know, like serotonin syndrome, that you know, don't always see it. So I think it's really important to know what. So, Dr. Kane, Dr. Patel, what? What really is hit. Speaker 2 02:35 So I think the patient here cannot catch the break. And probably, Dr. Kane in your setting, you probably have experienced patient cases, but hit on our side, Dr. Schuman and the outpatient side, it is a super rare condition, unless somebody was diagnosed and now they are on a chronic anticoagulation, which we will talk about in a little bit. So it is a very rare condition which is immune mediated, that causes thrombocytopenia. And basically what happens is the platelet counts decline. And with that decline of platelet counts, there is actually a higher risk of thrombus formation. So there is cases of hypercoagulability. In our patient case, she did develop a new thrombus. This is Dr. Sean Kane 03:18 actually what opposite of what you would think it would be. So typically, when you think of low platelet counts, you think about bleeding, but in the case of hit, because of this immune mediated response, it actually activates your platelets, and that platelet activation causes a thrombus anywhere in your body, and the arteries and the veins, doesn't matter. So it's really the opposite of what you might expect in terms of bleeding risk versus clotting risk. As a student, Speaker 1 03:41 this was something I always wrestled was like, but, you know, in Latin terminology, we learned about things and words meaning drop, and then this drop that causes an increased risk, and I'm glad to hear you say the counter intuitiveness of it, because it was my brain at the time, and even maybe still today, it was still trying to wrap around that whole dichotomy. Speaker 2 03:58 So there must be an interesting pathophysiology behind this? Yeah. Dr. Sean Kane 04:02 So basically what happens is the platelet cells themselves release this protein called platelet factor four, or PF four, and for whatever reason, PF four, this protein that your body makes, can form a complex with heparin molecule. So this is heparin Most commonly, or even low molecular weight, Heparin, like enoxaparin or Lovenox. So this complex is actually what your body can form an immune mediated response to, and in the case of hit, that immune mediated response is an IgG antibody, and that IgG antibody, when it finds this PF four heparin complex, it activates so that IgG antibody will activate platelets, and that platelet activation will form clotting. It will consume platelets. You'll get thrombocytopenia as you form this immune mediated response. Speaker 2 04:52 Well, that's a very interesting mechanism of how a clot can develop, even though platelet counts are going down. But once again, to emphasize. Is that, you know, the true diagnosis of hit is very rare, but patients in the hospital can have many different reasons to have low platelet counts, but thrombocytopenia, Dr. Sean Kane 05:10 and that's really the challenge here. So hit comes up so commonly, at least in the inpatient side, because we see a ton of patients with thrombocytopenia, but we don't actually see true hit that often, but it's always something that we're worried about, because if you have true hit, your risk of dying is actually quite high. Your risk of having arterial thrombi that cause you to have amputations or you to get very, very sick, that is actually fairly high. So it's one of those very rare but very serious complications of something that we do commonly in many patients in that hospital setting, which is VT prophylaxis with heparin, or low molecular weight heparins. Speaker 1 05:45 And so when I was in school, I briefly remember us talking a little bit about this, this idea about a 4t score as a way. And again, I don't really employ some micron most of the time when we see, you know, thrombocytopenia, it's on the outpatient setting, more like things medication induced, for example. So, but this 4t score seems to be something that we can maybe use to to kind of suspicion of it. So can you tell me a little bit more about that? Dr. Sean Kane 06:05 Yeah, so you know, for the purpose of an audio based podcast, we can't go into every detail. There's a lot to it, and I would really encourage the listeners to look at the review article that's posted at HelixTalk.com this is a citation by Salter and colleagues. 2016 it's a really good review that includes the 4t score in a table format. But in terms of what is the 4t score, it's four different things to think about in terms of whether this patient may or may not have hit. It's to help you decide what is your actual clinical suspicion of hit in this patient. Speaker 2 06:38 So I bet all the 4t start with the t1, would think. Dr. Sean Kane 06:41 But in this case, it doesn't. The first three do start with a T, so it's thrombocytopenia, timing and thrombosis, and then they kind of copped out a little bit, and the fourth, what should have been a T, ended up being an O, and it's other. And they capitalize the T and other to get to their 4t maybe O, silent. It's a silent O. So we'll start with the first T, which is thrombocytopenia. And this is the one that everyone thinks about when you think about hit, because the T in hit is thrombocytopenia. What they're really talking about here is the trend in your platelet count over a period of time. So the highest clinical suspicion of hit is in someone who has a platelet decline rapidly of more than 50% and that platelet count still stays above 20,000 so in hit it's very rare to have profound thrombocytopenia, but it's very common that you'll have these massive, rapid declines of more than 50% of your platelet count. And again, clinically, this is the thing that really sets off the alarm bells. But there's three other things that make up your 4t score, and that's what the value of this 4t score is, is to not just think about that 50% decline in platelets. Speaker 1 07:45 So I'm guessing that the next one has something with time. This sounds like another nice, alliterative T word, exactly. Speaker 2 07:51 So here, you know, as we said, this is an immune mediated reaction. If we know about the immune mediated reaction, sometimes it takes a while for our body to develop this IgG antibodies, right? So the suspicion is very high if the decline of platelets occurs within less than a day, if patient has had heparin exposure within the past 30 days. So you know, patient has been exposed to heparin before, and now the antibodies are kind of ready to hit the platelets, and so the appearance of hit happens within a day of receiving that second time heparin. If the patient has not received heparin in past because IgG antibodies take a little bit longer to develop. This appearance happened anywhere between five to 10 days of getting the heparin therapy. Dr. Sean Kane 08:38 And then the third T is thrombosis. And if you go back to our patient case, this again, is one of those things that will set off the alarm bells in someone who's especially if they're on, let's say, a heparin drip or full dose Lovenox, and they have a new clot while they're fully anticoagulated, that should always raise a huge alarm bell in terms of, why did they develop a clot while they're on an anticoagulant? And in this case, in our patient, she wasn't fully anticoagulated, but we were given her DVT prophylaxis, so any new clot may be a sign of hit with another T, So, h, i, t, t, that's hit with thrombosis. And the worrisome thing about hit is that you could develop a clot by activating these platelets and forming a new DVT, an arterial thrombus, a PE, a stroke, an MI, any clot anywhere in your body. In addition to that, again, we kind of go away from the algorithm or the nomogram a little bit, and we add in here thinking about, did the patient have any skin manifestations or allergic type reaction to the heparin? And if they did, we kind of group that together within this thrombosis type category. Speaker 1 09:40 And so then the fourth category, and kind of a cheat, wouldn't be the other causes, again with a capital T or a silent O. So yeah, 3t plus O probably didn't sound as catchy. Dr. Kane, so both of the 4t so thinking about hit, one of the things we look at is some of the other causes of it. Again, I think medications, where we think sometimes with something like Depakote and seeing like a thrombocytopenia. Or a pancytopenia, but other causes too, things like infection or surgery, trauma, hemodilution, intravascular devices, a balloon, pump, CRRT, something like that. There's a lot of other things. And so it becomes almost, I guess, a diagnosis of exclusion, to some extent too, that you're looking for Dr. Sean Kane 10:15 these other factors. Yeah, and this is clearly the most subjective item within our 4t score, which is one of the reasons why this scoring system is beat up a little bit, is that inter rater reliability may not be as good because of this one item. In terms of Dr. Schuman, you mentioned valproic acid. I'm sure you see a lot of that in your clinic. Oh yeah, I see very little of that in the ACU, but I see a lot of beta lactams that we give high doses of, that which are potentially implicated in causing drug induced thrombocytopenia. So in terms of what's on your radar, what do you constitute as like a very likely cause or not that can cause some subjectivity here, but really what we're concerned about is the patient example that we started with, she has almost no reason to have new onset rapid thrombocytopenia. Something is different, right? And the fact that there is no other clear cut cause, should again raise that red flag in terms of is this hit or Speaker 2 11:06 not just combining the 4t that we just discussed. Remember, 4t score is to rule out the hit, but it cannot confirm the diagnosis of hit. So all these different category we talked about gives a patient a score anywhere between zero to two for each of the four categories. So if the score is low, then the patient almost does not have hit. But if it's four or higher, then we probably need to do more testing to confirm hit again. 4t score does not confirm the diagnosis. Dr. Sean Kane 11:36 And the way I think of the value of a 4t score is to basically not send off confirmatory testing to save everyone the time and hassle because it is so rare that hit actually happens, this is a way to kind of stop and say, No, it's not hit. Don't worry about sending any additional testing. So in our patient as an example, again, I would really encourage the readers to take a look at that table in the review article that we referenced, because there's a lot more detail there. But her 4t score is either a seven or an eight, depending on that fourth category, the other category, because her score is four points or more, we have to do more testing to see if she may or may not have hit Speaker 2 12:11 so what are these different tests that we can do to confirm after performing a 4t evaluation? Speaker 1 12:17 So as Dr. Kane mentioned again, we've got the scoring done. So if we, if we know the rather than just just test everyone, to save a little bit of time and effort again, go ahead and if the score is high, you start with a hit IgG antibody test. And again, if it's positive, there, do we have an answer? Dr. Sean Kane 12:33 Unfortunately, no, and this is for sure, that the most common problem and in terms of the diagnostic workup for hit people confuse this all of the time. So the IgG antibody has a very high false positive rate. So if that antibody is positive, it means you have the antibody, but that antibody may not be causing the syndrome we call hit so the only value in that hit antibody is if it's negative, if it's negative, you do not have the antibody, therefore you cannot have hit Case Closed. But if it's positive, we have to do even more Speaker 2 13:02 testing, and that test would be so it's Dr. Sean Kane 13:06 called a functional assay, where not only are we looking Do you have the antibody, but we're looking at, can we anger that antibody by throwing some heparin on it? So we literally take the patient's blood and add heparin to it and see, can we activate that platelet using the heparin that we add in this test tube. And there's two flavors that are commonly used of this functional assay. One is called an SRA, a serotonin release assay, and then the other commonly used one is called a HIPA test, H IPA, and that's a heparin induced platelet activation test. And both of these are really, really good, so they give you really high specificity, really high sensitivity. And what do you think is the most common question when I tell a student that this is like the best test for hit, how long does it take, and how much does it cost? Exactly? And that's really the two problems with SRA or the HIPA test, is that it takes a long time to come back. We're talking a couple days in most institutions, and it costs a lot more than sending the hit antibody test. So at this point, really, from a diagnostic workup, we've tried to do as many things that we can to not send the SRA or the HIPA, because it takes so long and it costs so much money. So we look at the 4t score to argue that we shouldn't send anything else. We look at the hit IgG antibody to say, well, the antibody isn't there. So we don't need to do this more expensive, lengthier test. If we get to this point, we truly do trust the results of the SRA or the HIPA Speaker 2 14:29 test, and once the tests are positive, how do we treat the patient? Is another component that we should discuss. So again, because the name says it's heparin induced thrombocytopenia, the culprit over here is Heparin, or any type of low molecular weight heparin. So we should stop all different forms of heparin that patient is receiving. So in our patient case, she was receiving the prophylaxis, heparin three times a day. But we should also look out for any type of heparin flushes, any type of devices they might be. Be impregnated or coated with the heparin. They all should be removed now. Speaker 1 15:04 Dr. Kane, do we wait till we get the this assay test back before we stop the heparin? Because, again, it seems like at that point we've delayed enough time so, like, what's the what's the timeline there? Dr. Sean Kane 15:14 So if you're worried enough about hit to actually send off your diagnostic evaluation, you really should, at a minimum, stop all forms of heparin. If your clinical suspicion is very high, you'll actually initiate therapy for hit empirically until you know, based on your confirmatory testing, whether the patient truly has it or not. So everyone, if you're going to send off the test, everyone, you will DC all heparin products and forms. If your clinical suspicion is really high, you're going to initiate your drug of choice, which is argatroban in those patients, and tell you can either prove that they do or don't have hit and then act accordingly based on that. Speaker 1 15:50 Now argatroban, again, I think of the name of it. It looks like something like, you know, the band person. It kind of sounds like Dabigatran, so I'm assuming the mechanism of action pretty similar Speaker 2 15:59 there, correct? It's a direct thrombin inhibitor, but unlike dabigatran Dr. Schuman, it's not an oral drug. It's an IV continuous infusion. So that's administration wise. It's a little bit of a hassle for the hospital team, and Dr. Sean Kane 16:12 it's kind of like heparin and how we adjust and dose and monitor it. So it is a continuous infusion. Dosing is highly variable. There's a lot of inter patient variability. So the dosing is adjusted based on an aPTT just like with heparin, and typically the aPTT goal is very similar to the same goal that you would use for a heparin infusion, and it's always going to be institution specific. So the only difference, really is that, because the half life typically is shorter with argatroban versus Heparin, will will be rechecking PTTs more frequently, because you get to steady state faster. So we can adjust them quicker and get them hopefully to their goal, aPTT faster with argatroban and Speaker 2 16:50 this is going to be a full anticoagulation, right, and not prophylaxis dose of argatroban, exactly. Dr. Sean Kane 16:56 So like in our patient case, her 4t score is really high, our clinical suspicion is very high. We're going to fully anticoagulate her, even though she was only getting subq heparin for two reasons. One, we're really, really worried about hit. And two, she has a new DVT that we have to anticoagulate her for anyway. Speaker 1 17:10 So how is this drug eliminated in the body? I know, you know, always back in that renal versus hepatic Dr. Sean Kane 17:16 with argatroban, specifically, it's hepatically eliminated. But that isn't really the full story. We have a lot of data, especially in my neck of the woods, in the critically ill patient, that their dosing requirements are dramatically lower than a dosing requirement for someone like our patient case where they're healthy. So as an example, for a critically ill patient, especially if they have multi organ failures, they will literally need 10 times less of a dose than someone who has normal organ function. So in critically ill patients will initiate somewhere between point two and point five micrograms per kilogram per minute versus a normal dose. And someone with normal organ function, they're going to have a dosing requirement at least initially closer to two micrograms per kilogram per minute, so literally, a factor of about 10 times different. Speaker 1 18:01 So then, as far as other options to go with, one of the things I remember when I was in pharmacy school, talking with the resident at a time at arc on our critical care rotation, was this idea about fondaparinux, and whether or not that's really another option. So Dr. Kane, what's the what's the current thought as far as that medication? Dr. Sean Kane 18:16 So I'd say that the general thought is that you can use fondaparinux for hit treatment with a very small caveat. And basically the caveat is that the chemical structure of fondaparinux, it shares a pentasaccharide molecule with heparin and low molecular weight heparins. It's a pure Xa inhibitor, but because it has this little fragment of heparin, there's always a concern that that little fragment may induce this immune mediated response we call hit, there are a number of case reports. We're talking less than 10 case reports that fondaparinux may have caused hit, but the community as a whole has said that we have enough data that fondaparinux can treat hit, that those case reports, if they are true, it is exquisitely rare that fondaparinux would actually cause hit, and we have plenty of data that says that it's a reasonable treatment approach for the treatment of hit, Speaker 2 19:04 and it sounds like it, because it's a, you know, sub q injection. So if patient were to go home, they can, you know, don't have to worry about IV administration of argatroban. We can easily switch them to fondaparinux. The caveat, the second caveat here, is that it is has a long half life, and it's renally eliminated. So if your patient has a severe renal impairment, probably we're not going to be able to use this drug, and Dr. Sean Kane 19:28 I can tell you, like in the ICU setting, because therapeutics, Half Life is so long, even if you have good kidney function. Versus enoxaparin, let's say we're unlikely to use it very often, because we do so many procedures to our patients, we have to hold anticoagulation if they bleed, we want it to go away quickly. So I'm sure on the outpatient side, fondaparinux is used much more commonly than, let's say, on the inpatient side, especially in an ICU type setting. Speaker 1 19:51 So the next option we've got there bivalirudin, and again, this one, direct thrombin inhibitor, continuous IV titration to aPTT goal. So kind of, kind of similar, again, renally eliminated. So again, we've still got to keep an eye on the renal function here. Yeah. Dr. Sean Kane 20:06 And bivalirudin is interesting because it is FDA approved for PCI, so putting a stent in in patients with a history of hit, it's not approved for hit, but it has been studied for hit, whereas argatroban is the only drug on the US market currently that has an FDA approval for the treatment of hit, which was one reason why it is considered the drug of choice for hit. Speaker 2 20:27 And then the chest 2012 guidelines mentioned a few other therapies that are used for hit, but unfortunately, they are not in the US market. There are going to be recombinant hirudins like lepirudin or desirudin. And these are kind of derived based on the leech salivary glands. Unknown Speaker 20:44 That sounds delightful, that sounds delightful. Dr. Sean Kane 20:46 What's so interesting? Because I mean, leech obviously have to make your blood thinner in order to pull it out of you. So we said, Hey, that sounds like a drug, right? So they did derive it from leeches. When I was in school, I still remember learning about lepirudin. So when we talked about hit, we said, well, you're going to use lepirudin in these cases, or argatroban in these cases. Well, it turns out, two years after I graduated in 2012 they actually pulled lepirudin off the market. The manufacturer did. There was a lot of reasons for that to be pulled off the market, but that one is off the market completely, and desirudin is on the market still, but it's supported by literally, a study of eight patients, and I think five of them got active drug, and three got some other comparator drug. Really not a robust amount of data here to really support that use. And it's kind of not really a confidence booster, is it not so much? And really the only other one that is recommended by the guidelines is called danaparoid. This is a low molecular weight heparinoid, as the danaparoid suggests. So it doesn't have any heparin or heparin like fragments to it. But the manufacturer got rid of this one in 2002 so you'll still see these products mentioned in the chest guidelines, even though they're 2012 guidelines. But it's important to know that you can't use any of them because they're either not on the market or really not preferred because of poor quality data. So we're really back to argatroban fondaparinux, maybe bivalirudin, but mostly argatroban is a drug of choice for Speaker 1 22:10 hit and then Dr. Patel, you had mentioned, one of the nice things about fondaparinux is, from that sub q aspect, again, we maybe can, can have a little convenience with the dosing, but since they can't go home on an argatroban drip, what are we doing as far as treatment? Once we you know, have we treated them enough? When do we stop? Speaker 2 22:25 Well, I'll be uncomfortable to release the patient if their platelet counts don't come back Dr. Sean Kane 22:29 up Absolutely. So kind of our threshold is 150,000 because that's the definition of thrombocytopenia, as a platelet count less than 150,000 so if it's above that, we say, you know, they're probably resolving in their hit. But we also recognize that even at that point, they're probably still hypercoagulable, because of this immune process that makes you more prone to clotting. Usually, what happens is, once they hit 150,000 we say, you know what you're done with argatroban. We'll switch you to something different, and that something different, typically And historically, was warfarin, and the problem with that is that argatroban will falsely elevate your INR, so when you initiate warfarin, you can't tell what the patient's INR actually is. While they're on argatroban, it's going to be on the scope of this podcast, but there's a bunch of tricks and tips that you can do to kind of figure out what is their INR. Are they ready to be transitioned off of argatroban, I would encourage your listeners, if they get to that scenario, look at the package insert. The equations that are mentioned in the package insert are absolute garbage. But there is a better approach. In terms of you actually hold the argatroban drip, wait for it to go away, check the INR. That would be an argatroban less INR, and then using that INR is where you should go in terms of that, that bridging process, Speaker 1 23:41 and I know that, you know hits so rare, DOACs are so new, so I'm assuming we don't really have a lot to go off of, as far as actually using them. Is that correct? Dr. Sean Kane 23:49 We don't, and there's no reason that you couldn't use a DOAC, aside from no evidence supports it, but there's no biologic plausibility why a doac wouldn't work just as well as warfarin, for example, and Speaker 2 24:00 there is always an option to convert them to fondaparinux, if the renal function is all good. And you know, they get a full training on how to administer fondaparinux appropriately. Dr. Sean Kane 24:09 So then, basically, once you've either picked your warfarin, your DOAC or your fondaparinux, you're going to do that for four weeks in someone who did not have a thrombus caused by their hit, or they earn a three month duration if they did have a thrombus, just like we treat any other DVT or PE for a minimum of three months. So they're going to be on whatever you pick for either four weeks or three months, or potentially longer if they had other clots that kind of justified them to have a longer duration of therapy. Speaker 2 24:37 And this episode of having hit or even the h, i, t, t, the thrombus that developed from having the hit would put the patient at no more heparin for the rest of my life, correct? So this should go on to patient's little booklet on the medication that you know you are allergic to heparin. It should be documented at the pharmacies, especially in the medical. EHR, that patient has allergy to heparin? Yeah, I'm pretty Speaker 1 25:02 sure this is a good rule for again, making sure your documentation is good, your Med RECs are done, so we don't have to worry about this mistake. But could we give it again if we had to? Dr. Sean Kane 25:09 So there are very rare circumstances where you might and most of the data is in patients that had hit a long time ago. They did hit IgG proved that the antibody was gone. And again, the duration of that antibody is fairly short, 30 to 90 ish days. And if they've done that, and they really, really, really want to use Heparin, there are case reports where they've done that, but for the most part, unless you absolutely have to use Heparin, you're not going to re expose that patient ever in their lifetime again to Heparin, which is why you would add it as an allergy. So you get the drug alerts and things like that when anyone tries to order it for that patient, right? Speaker 2 25:42 And along with the heparin allergy, the diagnosis of hit should also reflect into the patient's EHR. Dr. Sean Kane 25:47 And what I love to do when we do have these patients is, at least in our EHR, you can add Heparin, you can type in heparin induced thrombocytopenia as the reaction. But then there's a comment section I love writing in what was the diagnostic process to prove that that patient had hit, because it's so common that people mess up the difference between the SRA or the HIPA test, the functional assay, and the IgG antibody. I'll provide the date what the results of those two tests were to really prove that this was not an incorrect diagnosis. That we did all the steps that are necessary to confirm the diagnosis of hit. Speaker 2 26:20 Excellent example of detailed documentation. Dr. Kane, Dr. Sean Kane 26:24 so the next question is, what's next for our lady that came in with that perforation? So of course, we're going to stop all of her heparin and low molecular weight heparins, but she has a new DVT, right? So at this point, you have to do something for her. You can't just do nothing and wait for testing to come back. Speaker 2 26:41 So I'm assuming that we're going to have to start her on IV argatroban, and then adjust her argatroban, dose based on the aPTT. Speaker 1 26:49 Yeah, again, I think we could also potentially use fondaparinux there. But you know, if you're thinking, okay, 75 year old individual impair renal function is probably there. So I guess we're probably leaning more toward argatroban in that patient, Dr. Sean Kane 27:01 especially for a female, because she gets that times point eight, five on her Cockcroft-Gault, it's unlikely that she'll be an excellent candidate, and she may be a poor candidate for fondaparinux. And really, at that point, we're going to send off our hit testing for her. So we'll initiate argatroban, and at the same time we'll send off our hit IgG antibody, and just for the sake of discussion, we'll say that that was positive. The next step would be to send either the SRA or the HIPA functional assay, based on your institution, whatever they like there, and we'll say that that was also positive. So now we've gotten our full confirmatory test for HIT, for the for this particular patient. Speaker 2 27:35 So I'm pretty sure two things should occur before she leaves the hospital, a we're gonna monitor her platelets, and, you know, make sure they come back up, but document the allergy to heparin in the EHR. Like you mentioned, Dr. Kane, detail documentation with the test results and dates, and then perhaps consider an outpatient anticoagulation plan, because she had a DVT minimum of three month treatment is ensued over here. So we are looking at, you know, either Warfarin or continuation of fondaparinux, if that was what's selected in the hospital, Dr. Sean Kane 28:07 I think that adequately wraps up a good discussion on hit with a full appreciation of how rare it is, and especially the diagnostic component, that that's really where the meat and potatoes is from a clinical standpoint, to fully appreciate who might have it, and How do you start the work up for that and interpret the results appropriately? So what are some key take home points that you guys got from this patient case? Speaker 1 28:29 And my big thing, again, as you said, is the rarity of it, but also the fact that there's, there's a lot of things that look like hit and that we can maybe want think it and so it's really important to rule, rule it out, and we have something like a HIT score, 4T score that could be used to rule things out. And again, make sure to do that before we see every patient that comes in with thrombocytopenia say, oh, that's to be hit. And we all freak out, yeah. Speaker 2 28:50 And then, you know, we can look at the IgG antibodies, but again, there is a high false positive rate behind it. So if you want to confirm that patient has a diagnosis of hit, then we should consider doing functional assays like the SRA test or the HIPA test, and if they come positive, it's a true diagnosis of hit. Dr. Sean Kane 29:08 And then for the listeners, if you want to get a more complete review of the topic, we have an excellent review article by Salters and colleagues, published in 2016 we also link to the chest guidelines. They're a little bit old, and they do include a number of drugs that are no longer available in the US market, but there's still value in some of the recommendations that are in there that are much more detailed than what we have time to get into during the podcast itself. So those references are available at HelixTalk.com episode 80. We love the five star reviews. We just took a look at those, and we've gotten a lot of those. And if you haven't done a five star review yet, would really dramatically appreciate your help with that, it helps other listeners find the podcast. So with that, I'm Dr Speaker 2 29:45 keen, I'm Dr. Schuman, and I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 29:51 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store search for HelixTalk and place your review there Narrator - ? 30:02 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.