Transcription
Another day, another video about bleeding and coagulation disorders. In the previous videos, we have talked about the D-dimer, that was mentioned, activator inhibitors, and the alpha-antiplasmin. They all talked about the genius, and it's an actual genius called thrombomodulin, which modulates the thrombin from being procoagulation into being anticoagulation. Genius.
With that being said, now let's get started. [Music]
Thrombomodulin: if it ends in -in, it's a protein. It's an integral membrane protein. What the flip does that mean? Let me tell you. In a previous video called Cell Membrane, I've talked about the cell membrane, which is composed of protein, lipid, and carbohydrate. The lipids are a lot, but proteins are the most prevalent. Now, those proteins are not just one-size-fits-all; they come in two types: integral membrane proteins and peripheral membrane proteins. The integral, they take the whole freakin' thickness of the cell membrane. They are the channels, the order carries, the art of the pumps, and other structures. And, by the way, they are the thrombomodulin. Then we have the peripheral proteins, and they make the enzyme, the receptor, the anchor, whatever. So, functions of membrane proteins are numerous, and please watch my previous video on cell membrane to learn more.
During this slide, I would like you to do without your stupidity just for two minutes. After the slide, you can retrieve your stupidity back. Please pay attention. Think of coagulation as two pedals in your car: we have the accelerator, or the gas pedal, or the throttle, and you have the brakes. Those are the accelerator of coagulation and the brakes of coagulation. More coagulation with this, less coagulation with this. Okay.
Thrombomodulin: integral membrane protein on the surface of endothelial cell, yada yada, we don't care. Thrombin plus thrombomodulin: we have the thrombin-thrombomodulin complex, or TTC. TTC will activate protein S, which in turn will activate protein C, which will inactivate the act of factors 5 & 8. Factors 5 & 8 are procoagulation. When you inactivate factors that are procoagulation, you end up with anticoagulation. So, in a sense, thrombin is exerting negative feedback on itself because thrombin is procoagulation; now it's involved in the formation of a complex that's anticoagulation. So, thrombin is exerting negative feedback on itself.
Now look at the magic. Let's talk about heparin for a second. Heparin works by activating antithrombin 3, which I've talked about in a previous video. Then antithrombin 3 will enact with thrombin as well as factors 9, 10, 11, 12. So, heparin just applied the brakes, just the brakes. With heparin, you get less coagulation. Okay, fine. Now notice the miracle called thrombomodulin. It converted thrombin into this TTC, this complex, which will inhibit coagulation. Thrombomodulin applied the brakes while releasing the accelerator simultaneously. Have the thrombomodulin release the accelerator because now you have less thrombin, baby, because you took all of the thrombin that was procoagulant, converted it into something that's anticoagulation. Now we have less acceleration and more brakes at the same time because now the amount of thrombin available in the plasma is low because all of the thrombin is now in the freakin' complex, and this complex is anticoagulation. So you are stopping bleeding by inactivating factors 5 and 8. This is 1. And you are decreasing the amount of thrombin, which is procoagulant, and this is number 2. You are applying the brakes while releasing the accelerator at the same time. See how genius thrombomodulin is.
Thrombomodulin, my hero, decreased the amount of thrombin and at the same time created a complex that will inhibit coagulation because thrombin is called thrombin. -in means protein, and -thromb means thrombosis. Thrombin is literally the protein of coagulation. When there is no thrombin, there is no clot; it's not going to happen. Got it? It's taking the fire and converting it into a fire extinguisher to put out the fire. Freakin' amazing.
So if you think of coagulation as an accelerator and a brake, it will make all of hemostasis and all of the disorders that we'll talk about later a piece of cake. So, accelerator brakes. Accelerator means more coagulation; brakes mean less coagulation. So, example: any procoagulant example here, including the thrombin, and here you can add all of the coagulation factors, all of them are accelerators. Now the brakes, the anticoagulant, the thrombomodulin, why? Because it took the thrombin from here, converting it into thrombin-thrombomodulin complex, which inactivated protein, or sorry, activated protein C and S, and inactivated factor V and factor VIII, and now it's anticoagulation. Heparin: heparin is a brake; yes, it's an anticoagulant, but heparin is not the actual hero; the actual hero is the antithrombin 3. Heparin just takes the whole credit.
So, because repetition is the mother of pedagogy: thrombin plus thrombomodulin, thrombin-thrombomodulin complex. This complex will activate protein S—S first, as before, safe, I don't care about English right now—S comes first. This will inactivate factors 5 & 8. So, protein S and protein C are brakes to coagulation; they stop the coagulation train; they are anticoagulant, and so is thrombomodulin. Chances are your professor never told you that, and that's why you're watching my videos, and I'm proud of you guys. I really like you; I would like to serve you and help you. So please subscribe and hit this bell. Follow me on Facebook and Instagram. I have many cases, over 90 cases on Facebook, and they are not available on YouTube. Also, if you need more cases that are even not on Facebook, go to patreon.com/medicals. I have 50 hematology cases, and they are available for a limited number of students. Thank you very much for watching. As always, be safe, stay happy, and study hard. This is Medicosis Perfectionalis, when medicine makes perfect sense. Medicine and sense: two words that don't go together. It's like saying airline service.