Welcome, everybody. It's a pretty big crowd for 4.30 and hematology-related critical care, so I'm very excited about this. So this is me. If anybody, I can sign this for you later, so you recognize me. But as Dr. Maves was saying, so I'm kind of an oddball on med-peds as my primary residency training, and then I went and did a hematology fellowship and then a critical care fellowship. So I get really, really, really excited about bleeding in the ICU as well as cancer critical care, as we'll kind of allude a little bit to, just background stuff. I don't have any disclosures to report for this talk. And what do I love? I love complex bleeding and clotting, critical care-related coagulopathies, and the critical care management of patients with cancer. And as my residents have pointed out to me, I'm a hematologist, I'm critical care, so I guess I am a real-life hematocrit. And always, always, always give 100% unless you are donating blood. Sorry, I am a nerd. Dr. Loverde will attribute to that. Some of the goals, I won't go through each of these individually, but these are some of the things that I hope to touch on. And the point of my part of this presentation is to bring things back to the basics, not to give some super complex talk where everybody's eyes glaze over. I want everybody to really understand the absolute basics of the lab tests that we're looking at, why we look at them, and also why we shouldn't rely on some of these lab tests. So if you define coagulation, this is if you just go into whatever web browser of your choice and you type in coagulation, it's pretty much as clear as mud. Transfusion coagulation, process that prevents excessive bleeding. Process of liquid, especially blood, changing to a solid or semi-solid state. That it's the dynamic process, balances between procoagulant and inhibition. Thrombohemorrhagic balance and complex interaction between procoagulants. Everybody get that? Makes perfect sense for your clinical care management. But if we go back just a little bit in some of our brief transfusion history, it's actually very fascinating stuff. All the way back in 1628 is when William Harvey discovered circulation of blood. Not certain what we thought was happening beforehand when people would bleed, but you know. Also in the 1600s, they were able to keep dogs alive by transfusing blood from one dog to another. Interestingly, you don't need to ABO match blood for dogs in transfusions. So this probably actually led us a little bit astray when bad things didn't happen to our animal models. Thinking that dogs were not the best thing to transfuse into humans and that lambs were very, very, very passive animals, we decided to, for patients who were mentally ill, uncertain what mental illness, to transfuse lamb blood into a human to try and temper that psychosis. The man survived. So did his psychosis. Thinking that we could do even better than animal blood, we figured that transfusing milk from goats, cows, into humans was a reasonable thing to do. And that process lasted a lot longer than it should have, but you know. In the early 1900s is when we discovered ABO blood types. And as we continue through, more and more complex blood management developed. And then we finally learned how to preserve blood so that it didn't have to be donated and transfused pretty much immediately. You could now actually store blood. During the Vietnam War is when this concept of a massive transfusion came into literature. We were doing this well before that, but this is when it started becoming more of an idea to standardize the 10 units of blood in a 24-hour period. And if you're really interested, Google massive transfusion, and you'll get probably about six or seven different definitions of what that means as well. To make a massive transfusion worse or less effective, we developed a code red, which suggests that transfusing massive amounts of crystalloid prior to the blood, we now know that that is probably one of the worst things you could possibly do in that situation. Shortly after that, probably because people were dying from that code red, massive transfusion protocols were developed that were component-based. And then we thought that we could do better than the human body by doing this component-based medicine. And then we proved that the human body knows better, and that transfusing whole blood likely is better than transfusing components. So when we talk about whole blood, whole blood is separated out into packed red blood cells, platelets, white blood cells, and plasma. This equals 100%. So if you have 15 grams of hemoglobin, you will have 45% hematocrit. That makes up the red blood cell component. Everything left over is your plasma. That makes up your plasma, your white blood cells, your platelets. That's where those numbers come from. And we'll talk about that in a few other slides about why we shouldn't be over-transfusing if somebody is euvolemic. Plasma, if you break down a plasma product, this is one of my big pet peeves. Not only my institution, at multiple institutions, we say, go ahead and transfuse FFP. My institution talks about transfusing FFP. What's the one thing that none of the patients in our ICU get? FFP. They all get something called PF24. So it's the plasma frozen within 24 hours, not the plasma frozen within eight hours, which makes it FFP, which has a detectable amount of factor VIII. For the most part, it doesn't matter. But for a hematologist, it makes me cringe. You also have thawed plasma. That's plasma that was prior frozen and is now thawed. You have liquid plasma, plasma that has never been frozen, cryopore plasma. This is if the supernatant has been removed. Freeze-dried plasma, pretty cool stuff, just needs to be reconstituted, can be stored on ambulances and other emergency medical service transportations. And then you have cryoprecipitate, which is plasma that is thawed, frozen, thawed, frozen, and you eventually pull off this enriched fibrinogen, factor VIII, von Willebrand factor, and factor XIII. Also contains fibronectin, which we don't really measure but is useful in coagulation. But even though you're pulling off some of these factors, this is really not a good product to use for vitamin K actor repletion. So define coagulation. This is one of the things I like to do with my hematology fellows as I'm rotating on that service and just define it for me. Let me see if you know what you're talking about. But before I get to the fellows, if you go to chat GPT, or I'm sure any of the other ones, you have superhero platelets coordinating with proteins. I kind of like that. I had to ask a 10-year-old relative of mine, and that was the outside Band-Aid is on the inside. That's pretty good. Asked one of my lawyer friends, what is coagulation? And it's a functional system, dynamic, but not independently, directly, or indirectly responsible for, or in contribution to regulating which may or may, but not guaranteed, excessive loss of desired loss aversion. Perfectly clear. My medical student said it was the reason for getting my first date and the cause of not getting my second date. Your hematology fellow there. Okay, so this is what we all learn about in medical school, or any other school. Like medical school, this is our coagulation cascade, right? You have this intrinsic pathway, you have this extrinsic pathway, they come together for the common good in the common pathway, and then somehow you develop this clot. And this does not actually exist. This exists in textbooks, this exists to torture medical students. It does not exist this way. Why do I say this? So if I asked you to draw out the solar system, this is probably something, if I asked a kindergartner to draw it out, this is probably something that they would do. This is equivalent to the coagulation cascade. Now why do I say that? This equals this. This is actually what our solar system looks like. But when you draw out the other thing, it doesn't look anything near that. Coagulation cascade is more like this. You have so many interacting proteins and products that all come together. So when somebody says, oh, why are they bleeding? There could be a hundred different reasons why this patient's still bleeding. I have patients all the time on my hematology consult side in the ICU that are bleeding with normal coags. Why are they bleeding with normal coags? Well, have to have a more in-depth understanding. You don't want to throw tons of products, because now you're consulting me because they're bleeding and they have a clot at the same time. Good luck trying to figure out what to do in that setting. So what are some of our standard coagulation assessments? These are the ones that we study. They identify lab-based ex vivo abnormalities. We extrapolate this to in vivo abnormalities. We don't shove these coagulation normalities and abnormalities into a box, but we actually shove them into a test tube. I'll explain what I mean by that. These are our standard coagulation assessments. I'm sure everybody is aware of the PT, PTT, thrombin time, plus, minus, maybe, eccrine clotting time. Probably only people who are really excited about bleeding, like me, are aware of this, and the bleeding time, otherwise known as a torture device. So you're pro-thrombin. How do we measure the pro-thrombin? So when I was a hematology fellow, we actually had to do this in a lab. It's not as simple. It is now as simple as just sending it down to the lab. You have to put it in a computer, and it spits out your results. But you actually add two different pipettes in your hand, and I had to practice this as a hematology fellow. So how do you do this? You have your test tube. You have two pipettes, and then as you push both pipettes at the same time, you have to drop your elbow, and you hit this little button that drops everything together, starts spinning it around for you, and the clock starts at the same time, so that you get your time based for the PT or your PTT. What they don't tell you is the way that this setup is, and you have both hands like this, and you have to come down like this. You have to move your head out of the way, or else what you do is you give yourself a black eye, which is really embarrassing to do. I didn't do that. We'll leave it at that. So you're pro-thrombin. So you're taking platelet-poor plasma plus tissue factor and phospholipid. You're incubating it at 37, throwing some calcium, and it is measuring our so-called extrinsic pathway. So anything along where these red circles are, any of that can affect what your pro-thrombin time is. Big huge pet peeve of mine, your INR is not a coagulation test. We pretend that it is. We extrapolate information from it. But your INR tells you whether or not your patient's on warfarin. Your INR is useful if your patient is taking warfarin, and they decide to travel internationally to another country, that when they do their PT there, and they're using different reagents, that their level of, say, 20 to 24, you might get that level back, that PT time of 24, and start freaking out that your patient is at risk. It may be totally normal for them to have that 20 to 24 based on the reagents. But they take that, and they calculate out the INR so that we can judge similar tests in that way. But your INR is not necessary. I have patients all the time that have elevated INRs, and the last thing that they need is product, liver failure patients, for example. Your PTT, now we're looking at our so-called intrinsic pathway here. And again, you're using platelet-poor-plasma, different activators, incubate it, record the clotting time. So pretty much the same test procedure-wise as the PT, but you're now trying to activate that intrinsic side of the pathway. Thrombin time measures the conversion of fibrinogen to fibrin. This is helpful, especially in the case of DOACs. I know we have a talk in a little bit on DOACs. But this could be helpful in that setting for DOACs. Your eccrine clotting time. This is one that as a hematologist I'll do every now and then. It's measuring the direct activation and conversion of prothrombin. So you take this protein that is isolated from a viper venom and mix it in. And it generates something called mesothrombin. Mesothrombin can be inhibited by a direct thrombin inhibitor, but not by heparin. So it's helpful for teasing out between the two of those. And this process is completely independent of calcium. The functional tests, Teg and Rotem versus the bleeding time. A Teg or Rotem lecture is an hour lecture in and of itself. I can definitely put up a slide, which I have here, and point out some different things. But truly understanding the complexities of this takes a lot of time. We use Teg at our institution. Very infrequently have I used Teg to give me a helpful answer. More often I've used it to reassure myself of an answer. While it is a real, quote unquote, real-time test, I still think it takes about 30 minutes at best for me to get the result back. And if my patient is bleeding, I'm not going to stand there for 30 minutes while I'm waiting. So for hematologists, Teg isn't necessarily the most useful test. It does have some really good evidence in the operating room. In my opinion, other than that, I think Teg is a solution looking for a problem. Bleeding time. Please don't do this. This is pretty much torture. This involves, if anybody has done these in the past, you pretty much inflate a blood pressure cuff on somebody's arm. And you're making some incisions on the lower, or more distal than the cuff. And you're blotting every X amount of time, waiting to see when the bleeding stops. It's highly variable, as you can imagine. And kind of not cool slicing your patients with scalpels for essentially no reason. So getting back to a little bit what we talked about before. So on average, if you have a 75 to 77 kilogram adult patient, and they have approximately five liters of whole blood circulating through them, 55% of that is plasma, 45% of that is your hematocrit, of which you can extrapolate that 15 grams will be your hemoglobin. So the question would be, what is the blood volume if your patient is non-bleeding? They're euvolemic, but they have a hemoglobin of 10. Let's try to think about that for a second. What if they have a hemoglobin of seven, or five, or three? So their whole blood volume is still five liters. This is why I made the comment earlier about being cautious when you're transfusing blood. Their whole blood volume is five liters. If you have a patient with a hemoglobin of three, which is not uncommon for me to have my sickle cell patients that have dropped their hemoglobin that low, or some of my other hemoglobinopathies or chronic hemolytic anemias to drop their hemoglobins that low, they still have five liters of whole blood. They're just plasma expanded. They come into the emergency department, they get not one unit, not two units, three, four, five, six units of blood at about 300 mLs per PRBC, plus some fluids on top of that. Well, you've just taken that patient and you've put them into a high output heart failure, which has a mortality of about 85% to 90%. So just be very, very, very cautious. I have a slide in a little bit that talks about transfusion thresholds. And again, transfusion thresholds, this could be a topic in and of itself as well. There are updated guidelines in the works. Just keep in mind that for the most part, almost always, less is more. The evidence for these specific thresholds is weak. So much of it is expert opinion. I'm on a guideline committee right now looking at updating transfusion thresholds. And while I have to be cautious with what I can say, I can promise you that there is no earth shattering recommendations that are evidence-based that are coming out. So less is more. So just follow all your institutional guidelines. And then for leading into Dr. LaVerde's talk, post-procedure, always ask yourself, did this patient, did this 85-year-old patient develop some unknown bleeding disorder in the past, you know, one or two hours during their procedure? Or is there a bleeding vessel? Or is a suture not tied tight enough? I joke with my surgical colleagues all the time. It's not you're not. It's definitely not you're not. It's the anesthesiologists that hit them in the elevator a little bit too hard there, loosen the knot there. Happy to take any questions at the end.

hematology

critical care

blood coagulation

transfusion practices

laboratory tests