Hematology ABSITE Review

Okay, welcome back to behind the nice ab site review today with Kevin, and we're talking about hematology and immunology. So let's start with some basics. The coagulation pathway. So Kevin, what factors are measured by P. T. T. So when we measure P. T. T. What factors are we measuring? Yeah. So all of the factors except for Factor vii great.

All factors except for Factor vii is, is, is what's measured with A P T T. And what's our goal, let's say in a patient that we're heparinized? What, what is our goal? P t T. Yeah, we want a goal. P t t between 60 and 90. Great. And, and the way I remember that too is there's, that's also a half-life. 60 to 90 is the half-life, 60 to 90 minutes.

So goal, p, t, t of of 60 to 90 with heparin whose half life is 60 to 90 minutes. Okay, Kevin, how about which measure of coagulation is best used to evaluate liver synthetic function? Yeah, so this is your

PT or INR, which measures factors 2, 7, Great. So your PT, INR, 2, 7, 9, and 10, those are all made by your liver.

So those are really your best indicators of your overall liver function. What coagulation factor is not? So 2, are synthesized in the liver. What factors are not synthesized in the liver? So that's factor eight and von Willebrand's factor. Okay, factor eight and factor and von Willebrand's factor are not synthesized in the liver.

Okay, so let's go through some different blood products and what the components of those blood products are and what situations you would want to use that. So for everybody listening, if you go to our, our, our ab site. Companion book there'll be a table that has these, but we're just going to kind of walk through them here briefly.

So, so Kevin, cryoprecipitate, what are the components of cryo? So that's going to have factor VIII, von Willebrand's factor, and fibrinogen. Okay, and what situations would you use cryoprecipitate?

So it's a great tool in hemophilia A, von Willebrand's disease, and hypofibrinogenemia. Okay, great. FFP, how about FFP?

What's, what's in FFP? Okay. I like this one because it's all the coagulation factors. Great. And some fibrinogen. Yep. So it's got all the coagulation factors. Got a little, some fibrinogen in there. And when do you use F F P? Any coagulation disorder. Okay. So yeah, you can use F F P for really any, it's kinda your go-to for somebody who's bleeding.

Platelets. What's in platelets? This one's pretty obvious platelets. Yep. So platelets, the component is platelets and you would use this for people whose platelets are low. So thrombocytopenia same thing for red blood cells. We won't go into that pack. Red blood cells obviously have red blood cells and you give it to people who are, or are low on, on their hemoglobin or as part of a balanced blood product resuscitation during trauma.

Now, how about PCC prothrombin? Complete concentrate what's in there? So it's the vitamin

K dependent factor. Okay, and these what do we use? What do you use PCC for most commonly? Yeah, it's best used for warfarin reversal. Yep. PC is a great thing to use for patients on Coumadin who are bleeding. So now we're going to go into some of our different transfusion reactions.

So this is the way you'll get this on the test is you'll have a patient who gets a transfusion for some reason, most likely anemia. And they develop a fever when receiving the transfusion and that should immediately make you concerned for a transfusion reaction. And we classify these as moderate or severe.

So let's talk about moderate transfusion reaction first, Kevin, what do you expect to see clinically for somebody who's having a moderate transfusion reaction? Yeah, so this person will generally have fever, tachycardia, headaches, urticaria, puritis, rigors, palpitations, mild

dyspnea, anxiety or restlessness, and flushing.

Okay, and what's your first step when you get this in real life and on the test? What's your first step, the next step? Stop the transfusion. Great, okay, stop the transfusion. And then where do you go from there with moderate to transfusion reaction? So you want to let the blood bank know that you're concerned about that and you need to see the patient immediately.

Send the blood unit, send, I guess, send the unit of blood that you're transfusing so that they can evaluate it. Okay. So then you send the unit of blood that you're transfusing so they can evaluate it. You send a urine sample and blood samples from a vein opposite of the infusion site for evaluation.

Okay, great. And you're looking for what actually, what are you looking for? It's like hemolysis. Yeah.

Yeah, I guess. I don't know.

Well, we'll just skip that. Okay. And how about how about some medications that you can give? So you can give antihistamines and antipyretics. Okay. And what else? Yeah, you definitely want to get some antihistamines and some, you know, antipyretics, but what else can you give?

Also corticosteroids and bronchodilators if anaphylactic symptoms are present. Okay, great, okay. Now how about severe transfusion reaction? So they're going to have many of the same things, just kind of on the... Believe it or not more severe side. So they're gonna have fever, tachycardia, chest pain, hypotension, respiratory distress, headache, rigors, hemoglobin area, anxiety, restlessness, and unexplained bleeding.

I've said rigors twice in here and I said rigors. Yeah, I know.

Yeah, so that's right. So again, a lot of the same things, it's just more severe and they're starting to have some of those more concerning systemic signs like hypotension and unexplained bleeding. So again, how do

you manage these? Once again, stop the transfusion, notify the blood bank and see the patient immediately.

Send the unit of blood that they're being transfused and the urine sample and blood samples for evaluation. Okay, great. And what are your medical management IV fluids and then epinephrine and diuretics. Great. So, yeah, these are, these, like I said, they're hypotensive. They're, you know, systemic. They have bleeding.

They have the homolysis. So they need resuscitation. So IV fluids, you need a blood pressure support. And you need to keep the kidneys alive as well as you can add those corticosteroids as well as the bronchodilators. If, if. Anaphylactic symptoms are present. So Jason, do you say rigors or rikers?

I would say it correctly. I say Rikers. Yeah, I think that's probably the best way. Yeah. Okay. So let's move on to some some hematology and trauma. So, okay, so this is lemme start that over. Okay. So let's move on to hematology in trauma. So,

thromboelastography has. Become more wide, widely used and widely available, and it certainly is fair game for the test. It's a little bit difficult to talk through. So again, go to our our outside companion.

There's a a tag, a thromboelastography graph on there. As well as we talk about the definitions of some of the different components, the R time, K time, alpha angle the L Y 30 to make sure you have an understanding of what that looks like and, and what the principles are and what all those things mean.

Cause it can certainly is a fair game for the ab side in this day and age. So moving on though so we're, we're, let's talk about it. Some various bleeding disorders Kevin. So what's the most common congenital bleeding disorder? That's von Willebrand's disease. And what, what is von Willebrand's disease?

So with this disease, the platelets cannot adhere to the wall of the injured vessel. Okay. And there's three different types of von Willebrand's. So let's walk through those. So type

one, it's, which is the most common, so most type one von Willebrand's disease most common. What how do you define that? So there's a reduced quantity of von Willebrand factor.

Okay. And how do you treat it? So if we go back up and rewind about one minute, we said that cryo precipitate has von Willebrand's factors and you can also give desmopressin. Okay, good. Desmopressin causes release of some of that native von Willebrand's present that is there and as well as cryo precipitate, so giving additional von Willebrand's factor.

Okay. So type two, what's, how do you define type two von Willebrand's disease? So this is actually a dysfunctional von Willebrand's factor. Okay, and so it's there. It just doesn't work. So how do you treat it? So once again, you can give desmopressin or cryoprecipitate. Okay. All right, and then type three.

What is that? This is the complete absence of vulnerable event factor. Okay. Yeah, so it's not even there So, how do you how do you treat this

and how is it different from the other two? Yeah, so this one you can once again give again give cryoprecipitate or factor VIII replacement But desmopressin will not work Yeah, so yeah, the key there is that desmopressin, which causes, induces the release of von Willebrand's factor, will not work with people type 3 because they have complete absence of the factor.

What about a lab test? What do you, what do you see with von Willebrand's factor? So you're going to see a prolonged PTT plasmin levels of von Willebrand factor antigen Von Willebrand factor activity and activity levels of factor eight. I guess I asked that weird. I answered it weird. Yeah. Is it prolonged all of that shit or?

Well, you see prolonged, I guess, I think it's asking what tests you send and it's, it's kind of written weird. So I guess you would see a prolonged PTT, but you can also check for plasma levels of Von Willebrand's antigen. You can test

the activity. As well as activity levels of factor VIII. Okay.

Alright, I'll say it again. I'll say, yeah, okay. Just say it again. So, with the lab test, you're going to see a prolonged PTT. You can also check for plasmin levels of von Willebrand factor antigen. You can check for the von Willebrand factor activity and activity levels of factor VIII. Great. Okay. Okay.

So moving on from Juan Villabrans to some other bleeding disorders notably hemophilias. So hemophilia A and hemophilia B. So Kevin, with hemophilia A, what factor are you missing? And what do you see on a lab test? So, hemophilia A sounds sort of like 8, so you're missing factor 8, and this will have a prolongation of your PTT.

Okay, great. Hemophilia A, factor 8, prolongation of PTT, how do you treat it? So, you can give them factor 8, desmopressin, or cryoprecipitate. Perfect. Okay, how about

hemophilia B? So, this is factor nine and you're going to see a prolongation of the PTT. Okay, great. So factor nine, you also see a prolongation of PTT and how do you treat it?

Factor nine or FFP. Yeah. Factor nine or FFP. Great. Okay. Okay. So moving sticking with bleeding disorders, but now let's talk about some hypercoagulable bleeding disorder. So say you have a patient who has a DVT, they have a family history of DVT. So what does this make you concerned about? Sorry. Let me say it again. So let's say you have a patient who has a DBT as well as a strong family history of DBT. So what are you thinking about? Yeah. So I'm thinking of the common hypercoagulable disorders, the most common being factor V Leiden. And then you have your prothrombin gene defect 20210.

Protein CNS deficiency, antithrombin 3 deficiency, and hyperhomocystinemia. Yeah, so those are all your heritable blood bleeding disorder, blood clotting

disorders. Certainly somebody with a strong family history. So the factor 5 Leiden, which is the most common. Your prothrombin gene defect that, 2021 zero or two zero two one zero, however you want to say that protein cns deficiency antithrombin three deficiency and hyperhomocysteine anemia.

Perfect. So what's the pathophysiology between that factor five Leiden mutation, which is again, the most common, and we see it pretty frequently, but what's the, what's the pathophysiology behind that? Yeah. So factor five cannot bind with protein C. Okay, so that's the mechanism of action between your factor V Leiden, your factor V is unable to bind with protein C.

Okay, how about antithrombin 3 deficiency, how does it present and what's the treatment? Yeah, so this is those patients that do not respond to heparin. And what's the treatment so you can give them antithrombin three concentrate or FFP? Right. It's kind of counterintuitive, but if you

have a patient that does not, that they're giving them heparin and their PTT is not prolonging, they're not responding.

You may want to consider giving them a FFP, which seems a little counterintuitive, but that then can work with the heparin and and have them then respond to the, the heparin. So home was mentioned. homo, hyper homo cysteine anemia. So how do you treat patients with that? Yeah. So this is one that you can treat them with vitamins.

You can give them full acid and B 12 full gas to be 12 for treatment for hyper homo cysteine anemia. Perfect. And

let me mention that one.

So one that we didn't mention was antiphospholipid syndrome, which is also very common. So how do you diagnose this and how do you treat these

patients? Yeah. So most commonly you're going to see this symptoms of lupus prior DVTs or recurrent pregnancy loss. And these patients will have prolonged PTT, but they're actually hypercoagulable.

Okay. Yeah. So if you see that, that prolongation, they usually give you that in the question stem, that prolongation of the PTT, but clinically they're hypercoagulable. This is most likely due to an anti, you know, fossil lipid syndrome and this is caused by antibodies to cardiomyopin and the lupus anticoagulant.

How do you treat these, Kevin?

Yeah, so you treat these patients with a heparin bridge to coumadin. Okay, so we anticoagulate them, most commonly with a heparin drip, and then you can transition that to an oral anticoagulant, most commonly coumadin. Speaking of oral anticoagulants, there are Well, anticoagulants in general, they're becoming more and more common.

We're seeing a lot of patients on anticoagulation specifically a lot of these doacs that are out there. So let's, let's

walk through some of them and importantly, let's talk about their reversal agents. So these are commonly tested. So we talked about one already, but that's Coumadin or Warfarin.

So what's, how do you reverse people who are on Coumadin? Yeah, you have a few options. If you need immediate reversal, you can use PCC. If you need rapid reversal less than one hour, you can give FFP, or if you need a little more delayed, you can use vitamin K. Yeah, I guess the way I would look at that is, is you, you, How, you know, what's, what's happening with the patient?

Is it somebody with a life threatening, you know, head bleed? You know, PCC is, is, is becoming, it's, it's very expensive, but it's very fast acting and, and you can really kind of dial in and, and their reversal if the patient needs, if maybe you don't have PCC available to you or the patient also needs volume in that case FFP might be a good choice, it's also very effective.

And then if you are, have that

patient who doesn't necessarily have life threatening bleeding, but you do need to reverse them and you need to provide prolonged reversal, you know, vitamin K is a good option. And you do see pretty good results within about six hours. Now, how about Pradaxa? How do you reverse Pradaxa?

So they have a new treatment called Praxbind, which is a monoclonal antibody, and you can also use a dialysis. Yeah, so like, you know, the, the answer used to be for, for Pradaxa or Dabigat, how do you say that? Yeah. Dabigatrin. Dabigatrin? Yeah. Yeah. So yeah, the answer for Pradaxa, there used to not be a great reversal agent.

So dialysis was the answer on the test. But now with. Praxbind, the monoclonal antibody. And sometimes they'll just put that a monoclonal antibody is the answer. They won't actually use the brand name Praxbind. That's a, that is a an option now. So, for Prodaxa, dabigatran was a generic name, which is what they'll give you on the test.

Monoclonal

antibody or ine for reversal. Okay. How about Xarelto or Rivaroxaban? Yeah, so you can use andex A, which is recombinant factor 10 a. Yeah, recombinant factor 10 a index. So, again, they don't often use the brand name. So to make sure you know what these things actually are eloquence pixaban, how do you reverse that?

The same index or recombinant factor 10 a. Great. Okay. How about just heparin? How do we, what's you know, you have a patient that's, you're getting, you're heparinizing, you probably deal with this as a vascular surgeon. How do you reverse that, say, intraoperatively? Yeah, you give them protamine and give it slowly.

Okay, protamine sulfate, perfect. And then Lovenox or Noxaparin? Yeah, so you can use protamine in these patients. It's just not as effective. Okay. So less effective than with the unfractionated heparin, of course. So what is the, we, what's the mechanism of action of, of heparin now that we're as you mentioned it.

Yeah. So this potentiates antithrombin three. Okay. And so it makes it actually a thousand times more effective. So that's why those patients with that antithrombin three deficiency don't react to heparin and you, as you mentioned, you can reverse with protamine. What do you have to watch for as far as side effects of protamine.

Yeah, so protamine can cause profound hypotension and bradycardia, especially if it's given too fast. Okay, perfect. Let's say you have this patient that has been given heparin and let's say they have a surgery and then on post op day eight, you see that their platelets drop pretty significantly over 50%.

So what does this immediately make you concerned for? So pretty much any patient who has exposure to heparin and has a precipitous drop in their platelets, what do you should be concerned for? Heparin induced thrombocytopenia or HIT. Okay. Right. So, again, we see with this, you should see a platelet drop of over 50%.

And usually it's within five to 10 days of that heparin

exposure. We have a scoring system that we can calculate that either helps us rule in or rule out this as a, as a, as a possibility. What is that scoring system? That's the 4Ts score. So you look to see if they have thrombocytopenia, the timing of it, if they've had any thromboses, and other possible causes of their thrombocytopenia.

Okay, great. And how do you diagnose it? Yeah, so use an ELISA test testing for antiplatelet factor 4 for initial screening, and then to confirm it is the serotonin release assay. Great. And so, Eliza test antiplatelet factor for confirmation with their serotonin release assay or SRA. Okay. Most importantly, how do you manage a hit?

Yeah, so the most important thing is stop the heparin immediately and then you, you can, you're like a little cursor popped up and your cursor is numerous. So stop the heparin immediately including

any type of lovinox. And then you're generally going to start anticoagulation with something such as argatroban or bivalrutin or fondoparano.

Yeah, yeah. So, that's spelled wrong on the Paranox fund. A Paranox. I don't

know. I guess that's still right. Yep, that's right. So you definitely want to stop that heparin exposure immediately. And you know, depending on how,

sorry.

Yes, that's right. You want to stop the heparin immediately. And then one of those other agents, most commonly, probably the fondant paranox, but also our got our gantrban or bivalorudin our options to anti

coagulate those patients. It is worth noting that patients who have had, who have had hit and then are re exposed.

It can develop rapid onset thrombocytopenia. So it's not necessarily within that, you know, 5 to 10 days. It can happen very early within the 1st day after the re exposure. So just keep that in mind. How do we monitor lovin ox? You know, we have all these PTTs and PTs and all that stuff for the other drugs, but how do we, how do we determine the effectiveness of, of our Lovonox?

So you can check the factor 10a levels. Good. Perfect. Okay. Going back a little bit to talk about Coumadin, how, what's the mechanism of the action of Coumadin? So Coumadin inhibits vitamin K. A protein that activates vitamin case or VK or C, and this prevents the creation of factors, 10, nine, seven, and two, as well as protein CNS, right?

Okay. So it's all your vitamin K dependent proteins, which is why, as we mentioned earlier,

vitamin K is a great reversal agent for Coumadin two, seven Nine and 10 as well as protein CNS, which is why that sometimes you can see almost a little hypercoagulable at first, which is the idea behind the heparin bridge as we inhibit those protein CNS, which have a shorter half life than some of the others.

But yeah, absolutely. Inhibit your vitamin K dependent factors. It is contraindicated in pregnant patients. Keep that in mind. It is teratogenic, so don't use in pregnant patients. So you, we already mentioned this, we'll skip that.

So Kevin, let's say you start a patient on Coumadin and they develop skin necrosis. What's the name of this phenomenon and what causes it? Yeah. So you kind of alluded to it, but it's the warfarin induced skin necrosis. And so the mechanism of this is that there's

a short half life of protein CNS, which are actually natural anticoagulants.

So there's a brief period of time when the patient is actually hypercoagulant because the protein CNS have been inhibited. Yeah. And again, as I mentioned, this is, this is why we typically bridge patients with lovinox or heparin. The incidence is probably pretty rare. And, you know, there are a lot of people that are not bridging, depending on the indication for the anticoagulation, but just be aware that that is a thing and you might see it on the test.

We already talked about this too. Oh, let's go over it again. Okay, I mentioned some of those direct oral anticoagulants, the DOACs, that are becoming increasingly common in our elderly population as anybody who's on any type of trauma service can attest to. So let's go, we mentioned it briefly, let's go again over the, their reversal agents and let's talk a little bit about their mechanisms of actions.

So, uh, Dabgatran or Pradaxa, what's the mechanism of action? Yeah, so this inhibits thrombin directly and

then the old school answer is dialysis and the new answer is Praxmind and I'll let you pronounce the antibody that is generic. Yeah, just, just, you just have to know it's a monoclonal antibody.

I'm not going to try and pronounce it. How about a Pixaband or a Rivaroxaband, a mechanism of action and reversal agents? So yeah, this is again inhibits thrombin. The reversal for these is PCC. It gives a partial reversal or indexa which acts as a decoy receptor for factor 10a inhibitor molecules.

Yeah, so you can give PCC and, and people do it, you, it's not as effective as it is with Coumadin. You might get a partial reversal, but as we mentioned earlier, that indexa or that Recombinant factor 10 A would be the reversal agent of choice for, for those agents. Okay, so moving on to thrombolytics.

So t p a, what's the mechanism of action of t p a? So this activates plasminogen and breaks down fibrinogen.

Okay. And our normal fibrinogen levels are between two and hundred two, 200 to 400 milligrams per deciliter. How do you reverse T P A? So Aminocaproic acid? Yeah, aminocaproic acid re is reversal agent for t p A.

Okay. So, let's say we have a patient that we're thinking about using. So, a good example would be a patient with a massive pe who is becoming unstable. And we want to, we want to give them t p a we wanna give 'em thrombolytics. What are some absolute contraindications? Yeah. So if they have active internal bleeding, if they've had a recent GI bleed, if they've had a recent CVA cerebral vascular accident or neurosurgery, or if they have intracranial pathology.

Yeah, the way you might see this, you'll see maybe a patient with a brain tumor or something, or a patient that had recent neurosurgery and now they have a PE and they'll, they'll give that patient to you and just know that a systemic TPA would not be an Option because of that's an absolute contraindication

and that patient would most likely what they're trying to get you to go for would be a catheter to directed thrombolysis with interventional radiology.

So those are absolute contraindications to TPA. What are your relative contraindications? Yeah, so if they've had surgery within 10 days, if they've had a recent organ biopsy, a recent delivery or a recent major trauma and also uncontrolled hypertension. Sure, and then you'll have to kind of base the clinical scenario.

Obviously, if the patient's dying, I think we've probably all seen this, patients with massive PEs after surgery, and they will get TPA, and you just kind of have to bite off that, that's you might have to deal with some bleeding as a result. Okay, so that's let's move on to, so we're talking about hematology and immunology.

So let's talk about a little bit of immunology. So this is something we don't probably don't aren't as familiar with the surgeons. We don't deal with this a whole lot, but it is something that we are tested on. So when we talk about immunology, what does MHC stand for? It's like the. Major

histocompatibility complex.

I should probably say that.

Major histocompatibility complex. Major histocompatibility complex.

So we're going to be diving in a little bit on the cellular level here with immunology. So, when we talk about the major histocompatibility complex, the MHC, what are our two classes of MHC, Kevin? Yeah, so you have your class one and class two. Okay. And class one. What, where, where do we find class one?

Yeah. So these are kind of the identifiers of all nucleated cells in the body. Okay. So yeah, these are images class one, a, B and C they're present

on all nucleated cells. They activate CD eight cells. So they bind cytotoxic T cells. So image S class one binds cytotoxic T cells. Okay. How about MH class two?

Where do we find those? Yeah, these are a little more specialized. They present on the antigen presenting cells. Okay, so MH class 2 antigen presenting cells, they activate CD4 and they activate helper T cells. So they stimulate your, the antibody formation after B cells are interacted with.

So, the way I kind of remember that is your MH class 1 and CD8, So one times eight is eight in your image class two with your CD four, two times four is eight. So everything kind of multiplies up to eight. It's a stupid way of remembering it, but it's the way I always remember it. This is painful. It's painful. We should just skip to this. Not hopeful, but IL stuff is a little helpful.

What are the types of, what are the types of n t cells helper T cells release? Okay.

Okay. All right. Okay, so let's talk a little bit about those CD four and those CD eight cells. So your helper T cells, your CD four what do they do? So let's say, you know, you got CD two binds to it and that stimulates your CD four to release some things. What kind of things does your helper t cells release?

Yes, these release i l two i l four, and. Interferon. Okay. And what is IL 2? What is the role of those things? So interleukin 2. Interleukin 2 stimulates the maturation of cytotoxic T cells. Interleukin 4 triggers the B cells to mature into plasma cells, and then interferon

activates macrophages. Yeah. Okay.

IL 2 stimulates cytotoxic T cells for B cells to mature into plasma cells and interferon activates macrophages. So those are all released from your helper T cells after it's stimulated by that MHS or MHC class two. Okay. And then your cytotoxic T cells, which are stimulated or binds with.

MHC class 1. What is, what do your cytotoxic T cells do? Yeah, so they identify the non self antigens presented on MH class 1. Okay, perfect. Now, how about natural killer cells? Very cool name, natural killer cells. How do they identify their targets? So they recognize cells that lack the self MHC and they attack cells bound with antibodies.

Yeah. So they kind of recognize other, right? So if you don't have those self identified or those, those self MHC cells, these will natural killer cells will hunt these down, these cells down and kill

them. Okay. Let's go through some antibodies. So immunoglobulin M, A, G, D and E. It's important to know what they're responsible for and what their individual characteristics are, because these are sometimes tested.

So, these are all released by B cells for antibody mediated immunity. So, IgM, where, what are, tell me a little bit about IgM. So, these are secreted during primary immune response after initial exposure to an antigen. Okay, how about IgG? So, this is your secondary immune response. Yeah, so IgM is your primary, IgG is your secondary immune response, IgA?

So, this is your mucosal immunity. Okay, yep, some mucosal membranes are found near pyre patches in the gut, found in breast milk, you know, passed on to the infants through breastfeeding and really in all secretions. Okay. IgD?

So this is the antigen receptor on B cells. Okay, and IgE? This is the one that's involved in all allergic reactions and parasite infections.

Okay, great. Okay, okay.

How much of this are we really going to cover?

I don't think we should do the different hypersensitivities. I don't know. Maybe because I'm lazy. No, I think hypersensitivities are important. I'm worried about that. I don't know about these cytokines.

Yeah, I guess let's go through these cytokines. Okay, let's go through them.

Okay. So yeah, those are your important antibodies, some characteristics. It's good to have some familiarity with those. So you don't want to miss those easy points. Other one, other places where you can miss any points are on cytokines. So just remember what cytokines do. So TNF alpha where is it produced and what does it do?

So this is produced by macrophages. It activates neutrophils and macrophages to increase cell recruitment and further cytokine production. Okay, great. How about IL 1? So this is the main source is from macrophages, similar effect to TNF alpha and causes fevers. Yeah, so this is a fever inducing. So IL 1 is responsible for the fever, for whatever reason I've seen that before.

Okay, IL 6? So this increases the production of hepatic acute phase proteins. Okay, so yeah, your hepatic acute phase proteins, your CRP, your amyloid, your C3 complement, fibrinogen, haptoglobin, cerebral plasma, alpha 1 antitryption, those are all your hepatic acute phase proteins. And IL 6 acts on the liver and increases the production of these hepatic acute phase proteins.

Great. IL 8. So this stimulates your polymorphonuclear leukocytes. Leukocytes, also known as PMNs, and causes chemotaxis and

angiogenesis. Yeah, the big one there is like chemotaxis and angiogenesis, so IL 8 causes chemotaxis. And IL 10. So this decreases the inflammatory response. Okay. Good. IL 10 decreases inflammatory response.

That's important. Okay. Something else that will show up from time to time is your different hypersensitivity reactions. I, I always found these confusing, so it's really good to, to go through them. So again, there's a good chart in the book if you want to refer to that, but let's just walk through them.

So your type one hypersensitivity reaction, that's your immediate hypersensitivity reaction. What's the mechanism of action and what are some examples? So this is a patient has preformed antibodies and this activates the complement cascade. Yep. So IEG to mast cells and basophils bind together trigger a histamine response.

Are you reading something different than I am? Oh, sorry. I was reading the chart. What are you reading?

Oh, I was reading. I don't know what the fuck I was reading. You were looking at the hype rejection. You moved on. Oh, sorry. All right. Yeah. Okay. I'll just say, so the mechanism of action is the IGE is bound to math.

I'm just laughing. It's like how you tried to like play it. Anyways. All right. So this is IgE bound to mast cells and basophils and binds to the antigen. This triggers the release of histamine, serotonin, and

what, what else does it say? Does yours say? Oh, bradykinin. I didn't see that. Oh, yeah. Okay. Let me say that again. Okay. So an immediate hypersensitivity reaction is when the IgE binds to mast cells and basophils and this triggers the release of a histamine, serotonin, and bradykinin. Okay. And some examples?

So examples would be someone allergic to peanuts,

a hay fever or a bee sting. Yeah. So again, immediate hypersensitivity reaction, IgE mediated with mass cells. That's your type one hypersensitivity reaction. So yeah. Think of your peanut allergies or your bee stings. Okay. How about type two? This is a antibody mediated, right?

So antibody mediated. So what antibodies mediated? Yeah. So typically you're thinking of your IgG or your secondary immunity or IgM binds the cells and it's destroyed via cytotoxic T cells or the complement system. Okay. And what are some examples of this? So this is ABO incompatibility or hyper acute rejection.

Yeah, so think, you know, like think about your transfusion reactions for this one. So this is antibiotic mediated type 2 IgG, IgM Antibiotic mediated. Okay type 3 Hypersensitivity. So this is an antigen antibody complexes that are deposited on tissue The complement is activated in neutrophils attack.

Okay, and examples of this so you see this in serum sickness and in lupus Yeah.

Okay. So this is a immune complex deposition. So you have these antigen antibody complexes that are deposited into the tissue activates compliment neutrophils come in again, as you mentioned lupus is a good example, serum sickness. Okay. And then type four, this is your delayed type hypersensitivity. So how does that work?

So this is the antigen presenting cells present the antigen to the CD4 cells and the macrophages are activated. And what are some examples of this? So that's your ppd test that we're also familiar with in contact dermatitis. Great. Yeah. So type four delay type antigen presenting cells involves helper cells.

PPD test is a perfect example of that. Okay. So just know your, know your hypersensitivity reactions. Okay. So moving on. So, to transplant immunology. So just still talking about immunology, but

now transplant. So, when we talk about transplant immunology, HLHA So when we talk about transplant immunology we talk about HLA classes.

So what HLA classes are the most important when determining a recipient, recipient and donor match? So it's your HLA, A, B and D are. Okay, so A, B, and D are, these are again present, present on all nucleated cells. And, and these are the things we're looking for when we're looking to see who's a match.

So, something that's pretty high yield when it comes to transplants is different types of rejection. Their timing with regard to the transplant as well as their pathophysiology and perhaps most importantly the treatment. So, we're going to walk through these, these different types of rejections, transplant rejections.

So, Kevin, hyper acute rejection, what's the timing, mechanism

of action, and treatment for a hyper acute rejection? So, this is less than one hour generally these have preformed antibodies that activate the complement cascade. Okay. And again, what's the treatment emergent retransplant. Okay. Yeah. So bad day.

So hyper acute rejection that would obviously happen if you have, don't have for whatever reason that that's, um, the, the match a match donor and you have preformed antibodies that activates that compliment cascade and emergent retransplantation is the answer. Okay. So that's hyper acute.

What about accelerated rejection? What's the timing and mechanism action for that? Okay. Yeah, so this is days to less than a week kind of time frame. And so you have sensitized T cells that are responding to the donor HLA. Okay. So yeah, days to week or days to a week. You already have some subsidized T cells and what's the treatment for accelerated rejection?

So you increase the immunosuppression, you can give

pulse steroids, and you can consider antibody treatments.

Okay, so, moving on then to our acute rejections. So we talked about our, our hyperacute, our accelerated, and now acute. We, we break these down into cellular or humoral. I'm not going to say that. That's stupid. Oh, yeah, I guess so. So we break these down into cellular or humoral. And what's the timing and mechanism of action for, for acute rejection?

Yeah, so this occurs over weeks to months. So you can think of your kind of discharge patient following up in clinic at this point. And so for the cellular rejection, you have T cells that respond to donor HLA. For the humoral, it's the antibodies to the donor antigens. Okay. So the important, I think the important thing to remember, I don't know if it'll get broken down into these, you know, the different components cellular versus

humoral, but acute rejection is weeks to months.

And then what is the treatment? So similar as before, you can increase the immunosuppression, you give pulse steroids or possible antibody treatments. And then the only difference for the humoral is there's the option of plasma phoresis. Okay, great. So yeah, increasing immune suppression, pulse steroids, antibiotic treatments, and then possibly plasmapheresis.

That's your acute rejection, weeks to months. Okay, moving on now to chronic rejection. What's the time frame for chronic rejection? Yeah, this is months to years. And so this involves the T cells and antibody formation. Okay. And treatment you can increase immunosuppression or you can re-transplant.

Okay. Yeah. So some, ultimately these patients, you know, obviously there's a lot of caveats there, whether or not they're a candidate, you know, if their organ is refiling. But consideration of retrans plantation, but certainly increased immunosuppression for most of your rejections. Okay, so.

Let's talk about some

of those different immunosuppressants. So, let's just go through them. Okay, so steroids. You mentioned steroids. What's the mechanism of action? When do you use them? What are the side effects? So steroids inhibit inflammatory cells and attenuates the cytokine production.

These are used in induction, maintenance and acute rejection. There's a lot of side effects to include adrenal insufficiency and impaired wound healing. Okay. Another common one we see is mycophenolate. So what's the mechanism of action for mycophenolate? Yeah, so this inhibits de novo purine synthesis, which inhibits T cell growth.

And this is kind of used for your maintenance therapy and patients can have GI intolerance or pancytopenia from it. Okay, it kind of makes sense, right? If you're developing, if you're inhibiting de novo curing synthesis, you might see a pancytopedia. Okay, cyclosporine. So this inhibits calcineurin and decreases cytokine production.

This is

also used in maintenance. It has quite a few side effects, though. You have hepatotoxicity, nephrotoxicity, potentially hemolytic uremic syndrome, seizures, and tremors. Okay, so the key thing there with that mechanism is it inhibits calcineurin for cyclosporine, inhibits calcineurin, and that's distinguished from tacrolimus, right?

How does tacrolimus act? It also decreases cytokine production, but through a different mechanism. So what mechanism for tacrolimus? So that inhibits the FK binding protein, which decreases cytokine production. Okay, great. So, and again, as you mentioned, these are maintenance drugs and also can have some nephrotoxicity, neurotoxicity, AGI disturbances and impaired wound healing.

So, serolimus acts a little bit differently. And what does serolimus do? So this inhibits mTOR. which inhibits T and B cell response to IL 2. Okay, and what's the big again another maintenance drug, but what's the big side effect with sierolemus?

So once again oh sorry, with sierolemus you can have interstitial lung disease.

Interstitial lung disease is a side effect of sierolemus. Okay so how about the anti thymocyte globulin, ATG? Yeah, so this is a polyclonal antibody against T cell antigens. This is used for induction and acute rejection. The side effects can be cytokine release syndrome PTLD and myelosuppression.

Okay. Again, there's a good chart in the book. Just make sure you review that. Specifically, you know, a lot of these do similar things, but act through different mechanisms. And those are occasionally asked. I wouldn't say it's the highest yield. But if you, if you want to get to that you want to get from that 98th to 99th percentile, you may need to know those different mechanisms.

Okay. So, something that is a little bit higher yield are the opportunistic affections that happen with the immunocompromised transplant patients. So, what are some difference? What's So, Kevin, walk me through some

different opportunistic infections and what the treatments are. Yeah.

So, you can see Cytal Omega Virus, or CMV, and the treatment is ganglocyclovir. You can see the PCP pneumonia, also I, how do you say that? Pneumocystis gerovecchi. Pneumocystis gerovecchi. Pneumocystis gerovecchi. It's PCP, right? No, that's something different, I think. Oh, fuck. Okay. You can also see pnu, whatever.

I don't care. You can also see pneumocystis ish pneumocystis vei. And the treatment for this is Bactrim or Trimethoprim? Solfa. Methyl . Sulfa sulfa. Sulfa methol. . I'm not saying that. Just say back room. Just say Bactrim. Yeah. All right. So you can see Pneumocystis Gerovesi and the treatment for this is Bactrim.

You can see Epstein. Geroveci. Geroveci. What did I say? You said

Gerovesi. You can see Pneumocystis Geroveci and the treatment for this is Bactrim. You can see Epstein Barr virus and the treatment for this is decreasing your immunosuppressive therapy with the post transplant lympho lympho proliferative disorder or PTLD.

The treatment is once again to decrease your immunosuppressive therapy or give Rituximab. And then you can see BK virus and the treatment is to decrease the immunosuppressive therapy plus or minus some other drugs such as fluoroquinolones leflonamide. And Cytophavir.

Cytophavir. Cytophavir. Say that again. The fuck, man. Luf... How do you say that, everyone? Luflonamide? Luflonamide? Luf... Leflun... I don't know. Leflunamide. Cytophavir. This is not testable shit. Alright. Do

you want to start this whole thing over and just like, how do we, how do we, how can we go through this? Why don't we do this? Try one. Okay.

Okay. Yeah. So for the immunosuppressed patients, what are they at risk for? There's a few things. CMV treatment. You can give them ganglocyclovir. You can get the Pneumocystis Girovecchi. Treatment is Bactrim. Some of them will get Epstein Barr virus. The treatment is a decreased immunosuppressive therapy.

You can get the PTLD patients, also known as the post transplant lymphoproliferative disorder. And for these patients, you want to decrease immunosuppressive therapy, and also consider rituximab. And the BK virus, you can get the treatment for this is decrease immunosuppressive therapy once again, plus luphonamide sodiatophere.

You're so close! Sido, sido, what? Sidofavir. I've never ever seen that word in my life. For the BK virus, you can

decrease the immunosuppressive therapy, give them luphonamide, sidofavir, or fluoroquinolones. Perfect. Okay. Well, that, that's again, these are things we don't think about often. Unless you're a transplant surgeon or just off a transplant rotation.

It's good to brush up on these things before the ab site. So let's go into some hematology and immunology quick hits. You ready, Kevin? I'm ready. Okay. So again, let's talk about some factors. So factors, what factors are produced by the liver? All of them, except for factor eight and von Wilburn's factor.

Perfect. Okay. Which factor of all the factors has the shortest half life? Factor seven. Factor seven has the shortest half life. Okay. The mechanism of action of thrombin, also known as factor two. Yeah. So this converts fibrinogen to fibrin, which activates platelets. Right. Thrombin activates platelets by converting fibrinogen to fibrin.

Okay. Your mechanism of action. Actually, let me say that again.

Right. Thrombin activates, or just cut that whole part out mechanisms of action of antithrombin 3, AT3. So this binds and inhibits thrombin and heparin activates antithrombin 3. Great. Heparin activates 3 binds and inhibits thrombin. So you have a patient with a platelet disorder so you have a patient with a platelet disorder.

Okay, so a patient with a platelet disorder will have what coagulation lab abnormality? So they'll have increased bleeding time, right? So your PT may not be affected if you have a isolated platelet disorder So you need to look for that increased bleeding time. Okay Qubitin affects which portion of the coagulation cascade, the intrinsic or the extrinsic?

That's the extrinsic, also known as WEPT, warfarin extrinsic plus PT. It's not also known as

extrinsic. A good way of remembering that is WEPT, warfarin acts extrinsically and you test it with PT. Say it again. Extrinsic.

And a good way of testing that, extrinsic, and a good way of remembering that is WEPT. Warfarin Extrinsic Factors, and you can test that with PT. Yeah, so WEPT, W E P T, Warfarin Extrinsic, PT is the test. Okay, what factors does warfarin prevent from being produced? Vitamin K Definite Factors, 2, 7, 9, 10 protein 10 CNS, perfect.

What's the most common inherited hypercoagulability disorder? Factor V Leiden. Factor V Leiden, that's right. Okay okay. What electrolyte disorder may you see after massive transfusion? Hypocalcemia. Right. That's the citrated bag. So that's why we well, there's a couple reasons we

might see it in trauma patients.

But after a massive transfusion from the citrate in the bag, you might see hypocalcemia, which is why it's important to give calcium for these, all these patients. Okay. Okay. So, let's, let's quick hit immunology. What is the. First immune cell to arrive at the site of injury. Neutrophils. Neutrophils are the first ones there.

What's the most common antibody in the body overall? IgG. Yeah, IgG is the most, common. What's the most common antibody found in the spleen? IgM. IgM is in the spleen. Good. What antibiotic is, has the ability to cross the placenta and provide some protection to the fetus? IgG. Right, IgG crosses the placenta.

What risk should patients undergoing splenectomy be counseled regarding outside the normal risk associated with the surgery itself? So, Opsy, or overwhelming post

splenectomy sepsis. Yeah. So that's we talk about this being that increased vulnerability to encapsulated bacteria. So you strep pneumo, H influenza, and Assyria meningitis.

And what's the process we talked about in the spleen chapter. What's the process by which the fuck we're almost there. Let's let, let me do that whole one over again. Cause I asked a question where.

So, Kevin, so patients undergoing splenectomy, what do you, how do you need to counsel these patients as far as risks of, of long term risk of, of, of not having a spleen? Yeah so there's a risk of overwhelming post splenectomy sepsis, also known as OPSI, so they have increased vulnerability to encapsulated bacteria.

Okay. And what are those bacteria? So strep pneumoniae, haemophilus influenza, and neisseria meningitidis. Yep. Yep. So those encapsulate the bacteria. Okay. So yeah, cause splenectomy decreases your IgM levels, T cell numbers, and lymphocyte proliferation capabilities. So those patients are certainly at risk for

OPSI longterm.

Okay. So hyper acute transplant recipient. The end. So, so transplant patients who undergo hyperacute rejection, what is the type of hypersensitivity reaction is this? That's a type 2 hypersensitivity reaction. And the most common malignancy following transplant? This one's tested all the time. That would be your squamous cell carcinoma.

Yep, squamous cell carcinoma. Perfect. Okay, well that wraps it up for hematology and immunology. Again, something we don't see every day. So, one of those things you just need to review and thanks for listening.