Transcription
Another beautiful day, another beautiful video about bleeding and coagulation disorders. In the previous video, we have talked about plasminogen activator inhibitor. Today, we continue discussing fibrinolysis by talking about the alpha 2 antiplasmin. If it ends in “in,” it’s a protein, and if it’s anti-protein, it’s probably gonna be a protein, because the active form of any substance in your body is gonna be a protein. Protein is probably gonna be produced by the liver. With that being said, now let’s get started. [Music]
This is what you miss when you don’t subscribe to a nice channel like mine. Please subscribe and save this playlist; it’s called Bleeding and Coagulation. This is just like a small sample of all my great videos. Just kidding, I’m a very humble person, because power corrupts, and absolute power corrupts absolutely. Please don’t leave this plasmin free; otherwise, it will degrade every single blood clot, leading to bleeding. We need checks and balances. Let’s put this plasmin in an inactivated precursor form called plasminogen. For this plasminogen to be converted into plasmin, we need TPA, which comes from the injured endothelium. Injured, not in the normal, because we need an evidence of injury in order to make a crucial decision like this one, because plasmin is crazy, and this takes few days, which is good because we need the clot to do its job and stop the freaking bleeding.
So here’s the story: prothrombin to thrombin; fibrinogen to fibrin; plasmin decreased fibrin to fibrin degradation products; the stabilized fibrin into D-dimer; and the fibrinogen into fibrin degradation products. What does plasmin do? It digests fibrin into fibrin degradation products. It digests fibrinogen into fibrin degradation products. It digests 5, 8, prothrombin, and 12. All of this can be summarized in one word: plasmin leads to hypocoagulability. Repetition is the mother of pedagogy.
Intrinsic and extrinsic coagulation pathways, with the vitamin K-dependent complex to convert prothrombin, and thrombin to convert fibrinogen to fibrin. Then we need plasmin to degrade the fibrin, but plasmin is present in a form of plasminogen, which is inactive. We need TPA or urokinase to activate plasminogen to plasmin. Now plasmin degrades fibrin into fibrin degradation products, the stabilized fibrin into D-dimer, the fibrinogen into fibrin degradation products. It will digest 5, 8, prothrombin, and 12. The fibrin degradation products will inhibit thrombin, because if you have enough fibrinogen degradation products, why the heck produce new ones? It’s crazy; it’s stupid. To understand fibrinolysis properly, think of thrombin and plasmin as enemies, but we should all love each other, okay, honey? The lawyer and the accountant both hate each other, but they are both necessary for the corporation. The professor and the administrator hate their guts, but they are both essential for a university to function. Okay, it’s just the way it is.
I have 50 hematology cases that cover topics like bleeding and coagulation disorders. They go through all of the platelet abnormalities and all of the genetic diseases about the platelets. So please go to patreon.com/drmekosis and get the cases. They are good for you; they will help you with your board exam. They are available only for 30 students; then the price will increase.
Three regulatory mechanisms of fibrinolysis. Now, how to inhibit and regulate fibrinolysis? We have three things: first, plasminogen activator inhibitor; alpha 2 antiplasmin; thrombin activatable fibrinolysis inhibitor, or TAFI. We have talked about PAI in the previous video. So how do we inhibit fibrinolysis? We have one, two, and three steps. Plasminogen to plasmin thanks to TPA. Who inhibits TPA or urokinase? Plasminogen activator inhibitor, because plasminogen activator is a fancy name for TPA, nice. Then plasmin, the free plasmin, is inhibited by alpha 2 antiplasmin. Then the process of degrading the fibrin is inhibited by TAFI. Plasminogen to plasmin thanks to TPA. TPA is inhibited by plasminogen activator inhibitor. Then we have fibrin into fibrin degradation products, and the stabilized fibrin into D-dimer. Plasmin, the free plasmin, is inhibited by alpha 2 antiplasmin. The free plasmin, however, the plasmin generated on the fibrin surface, #plasmin incorporated, forms a ternary complex, which means three, is protected from the alpha 2 antiplasmin, and this is awesome. The fact that the plasmin on the surface of fibrin is protected from the alpha 2 antiplasmin is amazing, because that’s how we will get fibrinolysis that we need; otherwise, fibrinolysis will never happen if alpha 2 antiplasmin had its way.
So here are the three regulatory mechanisms of fibrinolysis and how they work: quick summary. Who inhibits TPA and urokinase? Plasminogen activator inhibitor. Who inhibits the free plasmin? Alpha 2 antiplasmin. Who inhibits the process of degradation? Thrombin activatable fibrinolysis inhibitor. Alpha 2 antiplasmin is an active guy. If you’re active, you’re a protein. If you’re a protein, you probably come from the liver. Okay, it inhibits the free plasmin; that’s why alpha 2 antiplasmin is anti-fibrinolysis. Makes perfect sense, since plasmin is a serine protease; alpha 2 antiplasmin is a serine protease inhibitor. Remember what we call serine protease inhibitors? We call them serpins. Alpha 2 antiplasmin does not inhibit the plasmin that’s incorporated into fibrin fibers, as I’ve told you. If you have open-heart surgery, what the fancy doctors call CABG, the coronary artery bypass graft, will lead to decreased alpha 2 antiplasmin. When you decrease the antiplasmin, the free plasmin is left uninhibited. Plasmin goes crazy, fibrinolysis, and you may bleed. Also, if you have liver cirrhosis, since alpha 2 antiplasmin comes from the liver, when you have a liver problem, your liver is toast, you are not going to produce alpha 2 antiplasmin, and plasmin will have its way, leading to bleeding. And that’s one of the reasons we have increased bleeding tendencies in cases of liver disease. It’s not the only reason, but it’s one of the reasons.
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