Mechanism of Antiplatelet Interaction

by Carlo Raj, MD

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    00:01 From here we'll take a look at antiplatelet interaction.

    00:05 Now step back for one second, antiplatelet interaction, so what are we trying to do here? We're trying to, let's say on the arterial side, alright, arterial side.

    00:16 I want you to think of coronary arterial disease and that will be our prototype.

    00:20 And you should be thinking about atheroma.

    00:24 Can you picture that for me? Inside of the atheroma you have an LDL core, you have your foam cells, and so on and so forth, great.

    00:31 Well, these are drugs that would then break down your platelets.

    00:35 How do we go about doing this? Now, here's an important topic.

    00:39 Now, take a look at the picture here and begin at the cell on top.

    00:43 The cell on top is showing you the vascular endothelium.

    00:46 Now, we had a huge discussion in the very beginning of this entire section in which we discussed, one, that endothelium has been damaged, remind me what are you expressing underneath the endothelium that is then going to adhere to that platelet that you see there? Ah, VWF, von Willebrand factor, and that is going to be the ligand which is then going to receive the receptor known as which one? Glycoprotein Ib.

    01:18 That glycoprotein Ib, let's talk about this in two ways.

    01:23 Well, primarily one, but if there is a deficiency of glycoprotein Ib, what's the name of that disease? Bernard-Soulier.

    01:32 Next, our entire discussion here only dealing with platelet.

    01:37 You tell me clinically, what is the test that is going to represent the functioning of your platelet? Would it be PT, would it be PTT, would it be BT, or would it be D-dimer? If I told you that this picture and this mechanism is only dealing with platelet and it's not going to be PT.

    01:57 It's not going to be PTT or definitely not breaking down our clot, so it's not D-dimer.

    02:02 And the only test that could be effective will be bleeding time, period.

    02:05 Is that clear? I told you too.

    02:09 So glycoprotein Ib deficiency, increase in bleeding time, you don't have adhesion, you don't have adhesion, would be your Bernard-Soulier or you have a patient that has autoimmune disease such as immune thrombocytopenic purpura.

    02:27 Those of you that have memorized that ITP is the only autoantibody against IIb/IIIa is incorrect or should I say inaccurate.

    02:35 That autoantibody not only could attack IIb/IIIa, it could potentially attack Ib, keep that in mind.

    02:43 We don't really have a drug here for Ib but important nonetheless.

    02:48 What would we want to do next after adhesion? We want to activate the platelet, don't we? You tell me what's the name of that receptor that we have on the surface of the platelet? It's called P2Y12.

    03:01 So you're gonna identify P2Y12.

    03:04 So these drugs, we know more about this now.

    03:08 These P2Y12 receptors are for ADP activation.

    03:12 Now here are some drugs that you should know.

    03:16 On the very left, you see the drug called clopidogrel.

    03:20 I want you to focus on the suffix G-R-E-L, grel.

    03:26 From now on, you see a drug that has the suffix or has the letters grel in them such as prasugrel, such as clopidogrel, such as ticagrelor, and the other one may be ticlopidine you've heard of.

    03:41 All these are prototypic P2Y12 receptor antagonist.

    03:48 You'll notice it is pointing to ADP.

    03:51 It inhibits the ADP in your platelet.

    03:56 If that happens, if ADP never gets properly stimulated or activated, the platelet doesn't get activated.

    04:05 If the platelet doesn't get activated, guess what? It's you blood thinner, right.

    04:10 So from now on, you see the letters G-R-E-L, you should be thinking, oh ADP inhibitor.

    04:17 And if that ADP or a P2Y12 receptor antagonist and if that ADP is not activated, then the platelet will never express IIb/IIIa.

    04:28 Let's go ahead and take a look at that IIb/IIIa next.

    04:31 A couple of important things about IIb/IIIa, in fact, a multiple things.

    04:35 The first thing is, let's go ahead and try to take a look at the monoclonal antibody here.

    04:40 The name of that drug on the right as you see is called abciximab.

    04:44 Abciximab is a monoclonal antibody Fab fragment which is then going to particularly target IIb/IIIa.

    04:53 Now, why would you think about giving these drugs.

    04:56 Well, you might be thinking about giving clopidogrel, you might be thinking about giving abciximab in a patient that has 'aspirin allergies,' right? We all know what aspirin does so if you don't mind, I'm just going to very quickly mention aspirin obviously inhibits our COX pathway irreversibly.

    05:19 You're going to inhibit the functioning or creation of thromboxane.

    05:23 You're never gonna have or you diminish platelet aggregation.

    05:28 Correct, now if the patient has aspirin allergy, then you might be thinking about abciximab as an alternative.

    05:34 One down.

    05:36 Let's go ahead and talk about how maybe the patient has a type of hypersensitivity, has autoantibodies attacking IIb/IIIa.

    05:43 That would then be called immune thrombocytopenic purpura.

    05:47 There your focus is going to be on the fact that you have decreased platelet count and the patient is bleeding, purpura.

    05:54 Or let's say that your patient is deficient of IIb/IIIa.

    05:59 If you're deficient of IIb/IIIa, this brings us to a condition called Glanzmann's thrombasthenia.

    06:05 What are the tests that would be elevated, please? Good, bleeding time, excellent.

    06:12 Now, there's one last thing that I need to bring to your attention here.

    06:15 Inside the platelet we have something called cyclic-AMP.

    06:19 What do you know about cyclic-AMP? How do you break down cyclic-AMP, what's the name of that enzyme that you learned way back in biochemistry? It's called phosphodiesterase.

    06:30 There is a classification of drugs called phosphodiesterase inhibitors, a drug called cilostazol.

    06:37 Cilostazol is a drug that inhibits phosphodiesterase.

    06:40 You therefore increase the concentration of cyclic-AMP within the platelet, and guess what happens.

    06:47 You inhibit aggregation.

    06:49 Alright, it's a big picture.

    06:50 We're looking at platelet function and management only.

    06:54 You're thinking about a patient prototypically that has coronary arterial disease.

    06:59 You are trying to break down that thrombi and what we've down now is take in the discussion that we had initially with normal temporary platelet plug formation and along the way now, we have now put in some management drugs that you wanna keep in mind.

    07:15 A very important figure for you to have in mind so that when you know that you're dealing with a DVT versus an arterial thrombi, you know exactly how to manage it effectively.

    About the Lecture

    The lecture Mechanism of Antiplatelet Interaction by Carlo Raj, MD is from the course Hemodynamics.

    Included Quiz Questions

    1. Glycoprotein 1b
    2. Glycoprotein 1a
    3. Von Willi brand factor
    4. Factor 8
    5. Factor 9
    1. Bleeding time
    2. D- dimers
    3. Thromboplastin time
    4. Prothrombin time
    5. International normalisation ratio
    1. Platelets adhesion
    2. Endothelial rupture
    3. Solubility in lipids
    4. Solubility in polar solvents
    5. Fibrin activation
    1. Aspirin sensitivity
    2. Widespread skin necrosis
    3. Warfarin sensitivity
    4. Heparin sensitivity
    5. Cloumadin sensitivity

    Author of lecture Mechanism of Antiplatelet Interaction

     Carlo Raj, MD

    Carlo Raj, MD

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    great professor.
    By Cory Q. on 07. November 2018 for Mechanism of Antiplatelet Interaction

    I understand the explanation because he explains it slow and clear, also with very good clinical scenarios.