The "Fantastic Four" Differential In Thrombocytopenia

Added: 2026-05-20

[00:00:04]Thank you so much for having me and I'm so excited to talk to you about thrombocytoenia. Let's jump right into it.

[00:00:13]So platelets by definition really important in your body and less than 150,000 is the definition of thrombocyopenia.

[00:00:22]So when you have less than that it can occur from pretty much two reasons. The first is rapid destruction or not enough being produced. And so these are the two things that we're going to focus on today. Now the two main types are essentially autoimmune and drug induced.

[00:00:43]There are a whole bunch of medications that can cause thrombocytoenia.

[00:00:48]And this is just a short list of them.

[00:00:50]Now, don't try to memorize all of these, but just be aware that some of these are potential causes of low platelets. So, check that med list if your patients coming in from home and they have any of these medications as a reason for their thrombocytoenia.

[00:01:06]So, I'm a big fan of themes. The theme of this talk is four fantastic four of thrombocytoenia.

[00:01:14]and we're going to be discussing the four most common differentials that you should consider when a patient presents with thrombocytoenia. Granted, there are many others, but these are the four that are relevant for us in emergency and critical care medicine.

[00:01:28]Instead of boring you with a bunch of descriptions and textbook facts and on each of the four and the management, instead we're going to walk through cases on each one. And through space repetition, I'm hoping to embed these in your mind so that these fantastic diagnosises are what you think of each time you see a patient whose platelet count is less than that 150,000 that we just talked about. So, let's start with the first one.

[00:01:56]Meet Ricky. He's a 50-year-old male who's presenting with lightheadedness.

[00:02:02]And as you're completing your thorough review of systems, you learn that he's actually been bleeding quite a bit in his urine. He's just kind of gotten used to the bleeding and like several nose bleeds as a kid. And he notes it happens every night after he brushes his teeth sometimes. He's not taking any blood pressure, any blood thinner medications.

[00:02:22]And he hasn't seen a doctor for years.

[00:02:24]He did just come back from a resort vacation trip in Madagascar, pretty exotic, to celebrate turning 50 years old. While you're performing your exam, you notice he has this rash pretty diffusely. H keep this in the back of your mind as we'll get back to it later on.

[00:02:44]So, let's talk about the kind of labs you want to order.

[00:02:48]CBC, BMP, co-ag, and a bleeding patient.

[00:02:52]Certainly a typen screen. Well, dimer fibbrronogen. Are we going to go that far? Just when you get this list of labs, you come up with this brilliant idea because of his travel history and you think it's going to help you solve the case. A peripheral smear. Yeah.

[00:03:10]And you get one, but you totally can't remember how to interpret it.

[00:03:14]Thankfully, the lab did it for you. No blasts or immature cells, no hour rods, no sickling or shisha sites, sufficient number of all major cell lines noted.

[00:03:24]Platelet count of course deferred.

[00:03:28]Well, here are the rest of Ricky's labs and they come back and you ended up getting that fibbrin and the d- dimer which are both normal.

[00:03:39]So, which of the following does he have?

[00:03:43]Feel free to pause or take a moment and answer this question.

[00:03:50]If you thought of ITP, you are correct.

[00:03:53]Immune thrombocytoenmia perpa. So let's talk about it. It's a mouthful, so we're going to stick to calling it ITP.

[00:04:03]The results, it's the result of an autoimmune antiplatlet antibodies. And unfortunately, it's more common in women than in men.

[00:04:14]Thankfully though, the majority of these patients are not critically ill and don't need ICU level of care. And that's because their maps and blood pressure is typically stable. Sure, they'll complain about frequent and sometimes diffuse nose bleeds, but for the most part, their labs are pretty much none.

[00:04:35]So, what do we do for these patients?

[00:04:37]Well, it's a lot of supportive therapy.

[00:04:40]Outpatient involves some steroids, some IVIG sessions at infusion centers, and in really refractory cases that don't respond to medical therapy. It removes it involves removal of the site of primary clearance and auto antibbody production, which is the spleen.

[00:04:59]Retoxinab is also a medication and that can be used and it's important to know that sometimes patients can come with this on their medication list and this is just a monoconal antibbody that targets specifically CO CD20 receptor cells and is used for not just ITP but things like rheumatoid arthritis TTP and other types of vascularities.

[00:05:20]All right, so we're going to move on from Ricky and go on to see our next patient in the emergency department. And then suddenly you hear screaming from the ambulance triage area. All of a sudden they bring in this patient. He's a 38-year-old male named Benny. He's being held down by EMS and police. And so of course he comes to your resuscitation bed. Paramedics say the wife found him this morning acting confused and not at all like himself.

[00:05:47]He's normally a very sweet guy and he's just he's been under the weather lately.

[00:05:52]Hasn't really been drinking or eating at all. and he did have a good amount of diarrhea this past week.

[00:05:59]So, the nurse tells you all of a sudden he's got a fever. And on physical exam, you notice he's got that same annoying rash we saw earlier. And I'm an ultrasound guy. So, of course, we do an ultrasound and you see he's got a pretty full bladder. This is in addition to some of the other scans that we do.

[00:06:18]Well, with this full bladder, we're going to put in a foley. And when we put in the folio, the nurses say, "Doctor, this is what's come out." And he's not really bleeding from anywhere else exam.

[00:06:28]The fast exam is negative. So all of a sudden, we have a a very agitated patient who's febrile and has a pretty significant amount of hemateria with a weird rash that we're seeing.

[00:06:42]So, of course, we're going to get labs on this patient. He's is pretty concerning. There's a lot going on. And here are some of his labs.

[00:06:49]a lot more red this time than Ricky, our prior patient. And so I've made the labs larger for you to be able to see. He's got a luccoytosis.

[00:06:59]There's that thrombocytoenia of 90. He's got an AKI and his UA is positive for a UTI.

[00:07:08]You're going to get that smear again.

[00:07:10]And based on the previous case, the lab just kind of sent it to you anyway. And here's the interpretation. Decreased number of cell count. some immature cells and helmet or shisha sites noted.

[00:07:23]So as you think about this, one of your one of your first ideas is C diff. Hm.

[00:07:31]If he's got C diff, then we probably has a good explanation for his platelet count. But we have to think about what are some of the other platelet differentials that we were talking about that he may have. So again, take a moment and think about specifically what he could have with those labs. And again, this is a relatively young male who has a fever, altered thrombocytoenic, acute kidney injury, and that rash.

[00:08:02]Well, if you said TTP, you are correct.

[00:08:05]Thrombotic thrombocytoenia perate. And again, that's a mouthful. So, we're gonna say TTP.

[00:08:14]So, what actually and exactly is TTP?

[00:08:18]Well, this is an inherited or acquired deficiency of the Adams 13 gene. And this is needed for vonilibbrand factor.

[00:08:26]So, what happens here is you have vonilibbrand factor and Adam's 13 gene cleaves von willilibbrand factor into smaller multimer.

[00:08:36]Now those smaller multimemers can actually def go diffuse throughout the rest of the body and can cause some platelet clumping micro thrombus for formation and hemolysis and in severe cases pretty significant organ dysfunction.

[00:08:52]One of the ways I like to remember all of the things going on with these patients is brain fart. And I hope you don't have a brain fart when you're thinking of this, but it's a really good pneumonic as to the ways to remember it all. And it starts with brain which is confusion or altered mental status just like Benny had. Fever he also had that rectily. Anemia low hemoglobin I believe his was 8.3 renal dysfunction his creatinine was elevated at 3.38 and there's that thrombocyopenia.

[00:09:24]So how do we exactly treat it? Now it's a little bit beyond uh supportive therapy.

[00:09:33]Now in this case you're concerned for C diff with the diarrhea he had. Granted you'd want to treat the underlying cause. So antibiotics and and all of that but that's not the scope of this talk. We're talking about platelets. So yes there is a component of supportive therapy and there is a component of treating the underlying condition but you want to make sure everything else is being treated appropriately. In his case he had a UTI. So, you want to make sure you're giving him the necessary antibiotics to cover that as well. You also want to make sure you're avoiding nephrotoxic agents and making sure that that kidney injury isn't getting worse.

[00:10:10]You want to also trend a lot of his labs that creatinine could end up leading to some really bad renal failure that's long-term if not appropriately followed.

[00:10:19]And that's why it's important to monitor for any other additional nephrotoxic agents.

[00:10:24]Now, you can consider giving him steroids if he's failing to improve after getting the antibiotics, but at this point then you should start to seriously have a conversation about plex or platelet uh exchange.

[00:10:37]Um, and so we're going to talk just a very brief second about plasma exchange.

[00:10:41]And this is exactly what it sounds like.

[00:10:43]This machine, which looks a lot like a diialysis machine here, it actually uses the same process. The patient's blood gets removed through a plasma filter. uh and then they discard that plasma and the replacement fluid gets put back in um and it usually has pllets that are not missing that Adams 13 gene and thus helping replenish the patient's deficiency.

[00:11:04]So in some severe cases this can happen and uh patients would need pretty extensive monitoring to make sure there's no complications associated with this.

[00:11:14]All right, we're done with Benny and on to our next patient.

[00:11:19]This is Susie. She's a 48-year-old female who presents with shortness of breath.

[00:11:27]Although she's tested negative for CO 19, you diagnose her unfortunately with a severe multifocal pneumonia requiring 4 L of oxygen via nasal canula.

[00:11:37]She's told you very explicitly she's afraid of getting intubated after everything that happened during the COVID pandemic. and you assure her she's not gonna she not only does she not have CO, but she's tested negative for, but that you're going to admit her to the hospital and convey to the impatient team her wishes against not being intubated. Sorry to butt in here, but if you're enjoying this video, then I know you're going to enjoy the four free videos that we have for you in the link below. You're going to get four videos from the conference, Reus X last year 2025 that was filmed live in Philly. We have topics on airway, ECMO, ECGs. It's something you definitely want to check out. So, go to the link below, click download it, no questions asked. It's all yours. And back to the video. On your next shift, you want to go up and just visit Susie just to see how she's doing. And uh you saw that they increased her nasal canula to high flow nasal canula. At this point, she hasn't really been out of bed at all due to just being so tired and weak.

[00:12:35]So, you go to your ER shift, you see several other patients, and then the next day, you want to go back and check on Susie.

[00:12:45]Well, her bed is empty.

[00:12:48]Fearing the worst, you go and you check the EMR. Did something happen?

[00:12:53]Well, unfortunately, despite being started on high flasal canula, she remained hypoxic. She became very tacocartic and very hypotensive. She was started on BiPAP vasopressors and sent to the ICU.

[00:13:06]This whole time you're thinking, I really hope she didn't get intubated.

[00:13:10]Well, in the unit, she didn't. She's on BiPAP, and that's great. But she's still been on bed rest this entire past week and adamantly still refusing that intubation. She does not want the tube.

[00:13:23]You're curious what may have happened.

[00:13:25]Could this all be from her multifocal pneumonia? Why is this included in a talk about thrombocytoenia?

[00:13:32]Well, you actually are looking at her labs and she's doing much better, but you notice a trend as she's coming off of pressors. Her labs have taken quite the dip, specifically her platelets. So, let me ask you, which of these does she have?

[00:13:53]If you guessed hit, you are correct.

[00:13:57]That's heperin induced thrombocytoenia.

[00:14:01]So let's talk about hit. There are two types. Type one which is the benign type results from a direct effect of hepin on platelet activation. It occurs within 2 days of exposure and the platelets eventually normalize despite continued use of hepin. Even though it's self-limiting, you don't technically need to do anything about it. Most of these patients will still have Hepin discontinued and switch to an alternative anti-coagulant just to ensure that they don't have the worst type which is type two.

[00:14:34]Type two is certainly the more unfortunate and more scary one to be aware. So this is an autoimmune disorder and there are two anti there are auto antibodies against platelet factor 4 which activates and binds the platelets thus resulting in thrombocyopenia roughly 5 to 10 days after hepin exposure. So you definitely want to stop the hepin that's the first thing and then you want to consider switching to a gatraban. Now there are other agents you can consider fundoparanol or baler rudin though these are less commonly used it's super important that you send off an hit panel to test for the antibodies presence that way and the patient going forward will never receive hepin based on hepin based products again because this could always happen now it's super important that we do not give platelets because this can actually precipitate thrombosis Mr. T, I pity the fool.

[00:15:39]The reason I have him up on the screen is because there is the tea test that you could actually consider when trying to make this diagnosis and it's really hard. And so the scoring system uses four Ps each with the possibility of getting two points. So the first one is alternative causes. This is the stuff that we talked about earlier, medications, ITP or TTP.

[00:16:04]The next is well thrombocytoenia patients tend to have a fall greater than 50%.

[00:16:10]Next is thrombosis and this is new or recurring thrombosis with new with non-arithmmitous skin lesions such as necrosis.

[00:16:19]And then lastly time. It's really important that this occurred over a period of 5 to 10 days where that platelet drop needs to occur in less than a day with clear evidence of hepin being given. So to summarize all these for you alternative causes thrombocytoen thrombosis and time. This is the 4T test of hit.

[00:16:41]All right, your last patient. This is Johnny. He's a 37year-old male with a history of alcohol abuse who was complaining some belly pain before he immediately passed out.

[00:16:53]Here is vital signs and despite giving him several lers of fluid, he just remains hypotensive. He started on vasopressors and his lipase comes back through the roof.

[00:17:04]He also spikes a fever. So blood cultures are ordered and he's empirically put on broadspectctrum antibiotics before going up to the ICU.

[00:17:12]As you bring him to the ICU, you evaluate and notice there's that rash again. Have you noticed a trend? It's not really the most helpful just to have this kind of rash. Well, the resident just got done putting in a central line on this on the second attempt, unfortunately. And you notice where they stuck the first time, there's a good amount of blood oozing out. And even though the dressing and even through the dressing on the central line itself, this patient is confirmed not on anti-coagulation. His labs come back and he's got thrombocytoenia.

[00:17:47]His fibbrronogen is 72 and his d- dimer is 987.

[00:17:52]So which of these have I hope by now you are all choosing D at some point, right?

[00:18:00]No, but in all seriousness, he has DIC as a result of his pancreatitis. And so this is disseminated intravascular coagulation.

[00:18:10]So before we actually get into the weeds about what DIC is, we have to talk about thrombin.

[00:18:16]So thrombin is responsible for is a pro-coagulant essentially that converts fibbrinogen fi fibbrronogen into fibbrin.

[00:18:27]And so what this happens is the fibbrin is one of the building blocks for the entire coagulation cascade.

[00:18:34]And this thrombin then helps the fibbrin arrange itself into very very tight rows. These tight rows are then the building blocks that kind of go on top of each other to create this fibbrin mesh. And it's that fibbrin mesh that helps the body clock. And like I said, it's essential to the coagulation cascade. Thromben then goes on to activate factors 5 8 and 13 in order to make even more thromben to better help platelet aggregation. And so the cycle of clotting continues until anti-thrombin comes to turn it off.

[00:19:10]Now in DIC the issue here is that there's decreased levels of anti-thrombin and as a result widespread activation of thrombin. The bodies essentially can't turn thrombin off resulting in bleeding due to systemic platelet destru destruction and the widespread thrombin results in even more thrombosis and even more problems and even more issues with end organ damage like kind of like that we talked about earlier.

[00:19:42]So this patient is already experiencing multiple issues aside from the pancreatitis as a result of now their DIC.

[00:19:52]This is a four alarm fire. This is something that needs to be quickly recognized and it still can be caused by a whole bunch of other things. In this patient's case, it was pancreatitis, but it can also be caused by AML and solid tumors. It can be caused by an amniotic fluid bololis amniotic fluid embolism or other pregnancy complications such as placental abruption. Major trauma or surgery can cause it and sepsis can also so management is treating the underlying cause. In the case of Johnny, treating his pancreatitis with fluids and antibiotics is priority.

[00:20:32]Don't just prophylactically transfuse red blood cells because you risk fueling the fire essentially.

[00:20:39]Now the one other comment I have to make is the waterfall trial that was recently published which showed that aggressive fluid administration in pancreatitis led to increase likelihood of volume overload without improvement in clinical symptoms or clinical outcomes. So be cautious of how much fluid you're giving these patients.

[00:20:58]There are instances in which you would transfuse blood products and that depends on very specific lab values. So if your fibbrronogen is less than 100, you can consider cryoprecipitate. If your platelets are less than 20,000 or 50,000, then you'd want to consider transfusing. Or if the PTT is 1.5 times the norm.

[00:21:18]So lastly, if you're concerned about excessive thrombus formation being the more dominant than the bleeding problems that are occurring, that's when you would want to consider anticoagulation.

[00:21:28]This is a very tough decision.

[00:21:31]The important takeaway though is that although bleeding is the no most common number one sign, there's unfortunately no single sign, symptom, or test that can confirm the diagnosis of DIC.

[00:21:43]All right, let's recap.

[00:21:46]The definition of platelets is less than 150,000 and it can result from either not being enough produced or rapid destruction.

[00:21:56]ITP is an autoimmune condition due to auto antibodies against platelets and these patients can bleed but for the most part are hemodynamically stable.

[00:22:05]They have normal labs and most get outpatient treatment for severe cases.

[00:22:11]TTP is a deficiency in the atoms 13 gene and what's more important to remember is the constellation of symptoms that patients can present with. So that's why I like to remember it with brain fart which again brain for altered mental status, F for fever, A for anemia, R for renal failure and T for thrombocytoenia.

[00:22:30]The treatment is supportive therapy in treating their underlying cause. In severe cases patients can get an exchange transfusion.

[00:22:39]Hepin induced thrombocytoenia can be pretty difficult to diagnose. Um but that's why there's a 4T test here.

[00:22:47]Alternative causes thrombocyopenia thrombosis and time. Each of these getting two points maximum. Do not give platelets unless you absolutely have to as it's going to precipitate the thrombosis.

[00:22:59]And finally there's disseminated intervascular coagulation. Try to identify this as early as possible by looking at the patient's entire clinical picture and considering some of the several causes that we discussed earlier. Remember, there's no one single sign or symptom or lab test that can help you make this diagnosis. And then lastly, avoid giving blood products if you can. There are very specific times and lab values for when blood products, specific blood products at that may be indicated.

[00:23:27]Here's a table comparing ITP, TTP, and DIC. Don't worry about trying to memorize or take a picture of it. I have a little gift for you at the end. Same thing here. A little bit more detailed and complicated of an algorithm. Um, but all of these are going to be included in this handout. So, feel free to scan the QR code. It leads to a Google document where there's an outline of the entire talk that I just mentioned. It has complete uh uh details about each of the four differentials for thrombocytoenia.

[00:23:59]If you have any problems accessing the link, please feel free to shoot me an email at my email down here below or find me on social media at mammdo.

[00:24:08]Thank you again for joining me on this awesome trip to explore the differentials in thrombocyopenia.