Normal Hemostasis Clotting Factors

by Carlo Raj, MD

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    00:01 Now, what about the clotting factors? Most of them are produced in the liver.

    00:05 What are they again? I'll give you II, VII, IX, and X, and protein C and S.

    00:11 But the clotting factors II, VII, IX, and X, they're dependent on whom? Vitamin K.

    00:16 What's the name of that enzyme? Epoxide reductase.

    00:19 What's the name of the drug that inhibit that enzyme? It's called warfarin.

    00:24 What are all my vitamin K dependent factors? II, VII, IX, and X, and C and S.

    00:30 Now, at this point, I've repeated it so many times that that should be part of your permanent memory.

    00:36 Now, the one particular factor that will not be produced in the liver is factor VIII.

    00:44 Close your eyes, tell me about factor VIII again.

    00:48 Factor VIII, is that part of intrinsic or extrinsic? You got this.

    00:53 Part of intrinsic, isn't it? Intrinsic begin with which factor? Factor XII.

    01:02 What's another name for factor XII? Hageman Factor.

    01:06 We went from XII, we went to XI, then you went to IX, and you went to VIII.

    01:11 We spent time with factor VIII and I told you factor VIII required what for stabilization? Ah, there it is, von Willebrand factor.

    01:20 Who is the patient who is deficient of von Willebrand factor? A young lady and she had excessive bleeding during menses, right? Why? Because she didn't have the von Willebrand factor properly adhere to glycoprotein Ib nor did she have the von Willebrand factor to stabilize factor VIII.

    01:39 Now be careful, may I ask you a question.

    01:41 You all should know that when you're factor VIII deficient, what is the name of that disease? I'm sorry what was it? What if this patient comes in with severe bleeding in the joints and such? Doesn't even have to be a female, correct.

    01:57 This could be a young child.

    01:58 This is called hemophilia.

    02:01 Which one? There's two that you're responsible for.

    02:04 One is called hemophilia A, the other one is called hemophilia B.

    02:08 Well, do this.

    02:09 A comes before B, VIII comes before IX, therefore hemophilia A is factor VIII defect, hemophilia B is factor IX defect, okay? At this point, let's focus on factor VIII and know that it requires von Willebrand factor for stabilization.

    02:31 So the vitamin K dependent clotting factors are II, VII, IX, and X.

    02:36 Remind me again, which one are we missing? Protein C and S.

    02:40 Why are they missing in this statement? Because these are only the clotting factors that we're discussing at this point in time.

    02:47 What's the name of that carboxylation? Gamma carboxylation.

    02:52 What's the name of that enzyme that is required for gamma carboxylation? Epoxide reductase.

    02:56 Remind me again what the drug that will then work upon this particular mechanism? Warfarin.

    03:03 Let's talk about anticoagulants.

    03:09 Right, anticoagulants.

    03:11 So now that we formed a clot, let's break it down.

    03:15 The process is called fibrinolysis, isn't it? Why do we call it fibrinolysis? Because in order for you to have a stable clot, a stable clot, it was fibrinogen or was it fibrin? Fibrin, then how to break it down.

    03:29 Who helps with breaking this down? Who initiates or who cleaves your plasminogen.

    03:35 Remember, plasmin is the enzyme that will be responsible for breaking down your fibrin.

    03:43 Is that understood? Factor XII will help you do this.

    03:48 Next, the plasmin will then break this down.

    03:51 Now, what do you call it when you have excessive fibrin breakdown.

    03:54 What's the name of that particular test? Oh, these are called D-dimers, aren't they? So any condition in which you find excessive, breaking down a thrombi is obviously going to give an elevated level of D-dimers.

    04:08 So far I've given you three tests, PT for the extrinsic system, time please, 11 to 15 seconds.

    04:16 The PTT is the measure, which branch of the coagulation cascade? The intrinsic, good. The time there is 25 to 40 seconds.

    04:27 And here's the third test that I'm giving you, known as the D-dimer, which represents what, breaking down of your thrombi.

    04:34 So what about this plasmin and such? What's important about this? Well, we talked about how factor XII does it naturally.

    04:43 It's called tissue plasminogen activator.

    04:46 Fascinating, because aren't there some drugs that you should know in which your analog is a tPA? Sure. What's the suffix that you're going to be looking for? A-S-E, tenecteplase, streptokinase, alteplase, A-S-E.

    05:02 These are naturally acting tissue plasminogen activators or analogs that behave like the natural fibrinolytic agent.

    05:11 Then finally, under this discussion of anticoagulant, here are my vitamin K dependent factors that are anticoagulants, and which ones are these? Protein C and S, and here we have it.

    05:25 It summarizes ultimately that discussion or the discussion we've had throughout the entire time I've been telling you that we have six vitamin K dependent factors.

    05:34 Now, something else that I need to bring to your attention.

    05:36 If a patient comes to you says, 'Doc, I seem to have a little bit of pain in my leg down by the calf,' if they're giving you textbook, textbook type of presentation, upon dorsiflexion of the foot, use that for me.

    05:53 Dorsiflexion of the foot, oh there's pain in the calf region.

    05:56 The history goes on to say that she's a lady who is pregnant perhaps or maybe she's obese and maybe she is in a job in which she is not moving around much, or maybe she is on a transatlantic or transpacific type of flight.

    06:13 In other words, she's the perfect candidate of maybe developing a DVT, correct.

    06:18 When you have a DVT is the warfarin, is that the first drug that you're going to give, warfarin.

    06:23 Of course not. It's going to be heparin.

    06:26 Heparin works within seconds.

    06:29 Heparin works via antithrombin III. We'll talk about that.

    06:37 And then you must give heparin as a bridge therapy in a hospital setting via parenteral either IV or subcutaneous before you start giving warfarin.

    06:47 And the reason it becomes really important because protein C and S has a half-life that is so incredibly short.

    06:58 I emphasize short, why? If protein C and S disappear first and you're given warfarin, what are the only vitamin K dependent factors that are circulating in that patient's body? II, VII, IX, and X. You might have microthrombi taking place up and down the body.

    07:17 If you didn't get that, repeat what I just said please.

    About the Lecture

    The lecture Normal Hemostasis Clotting Factors by Carlo Raj, MD is from the course Hemodynamics.

    Included Quiz Questions

    1. Factor 8
    2. Factor 2
    3. Factor 9
    4. Factor 10
    5. Factor 7
    1. Factor 9
    2. Factor 6
    3. Factor 7
    4. Factor 8
    5. Factor 10
    1. 11-15
    2. 11-17
    3. 15-19
    4. 25-40
    5. 10-35
    1. Anti thrombin 3
    2. Protein C
    3. Plasmin
    4. Fibrin polymers
    5. Plasminogen

    Author of lecture Normal Hemostasis Clotting Factors

     Carlo Raj, MD

    Carlo Raj, MD

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