Transcription
Hey guys, it's Medicosis Perfeccionista Ellis, where medicine makes perfect sense. In the previous video, we talked about the anti-clotting mechanisms. Today, we'll talk about the pro-clotting mechanisms: how do you stop bleeding? So let's get started. [Music]
As you know, primary hemostasis is balanced on the dynamic, harmonious antagonism between the smooth endothelium, which is anticoagulation and thrombolysis, which are pro-coagulation. What are the factors that induce thrombus formation, also known as pro-coagulation factors, also known as thrombogenic factors?
First and foremost, the thromboxane A2. So let's play a game. Bring out a blank piece of paper and answer all of these questions: What is the function of thromboxane A2? Who makes it? From what? What's the enzyme? Try to answer them and then come back. Okay, are you ready? Let's do it.
Function of thromboxane A2: and the answer, of course, is increased platelet aggregation, bronchoconstriction; it's involved in Prinzmetal angina; so vasoconstriction, increased platelet aggregation, bronchoconstriction, and being involved in Prinzmetal angina. Who makes it? And the answer is platelets. From what? From prostaglandin H2 or from the cell membrane of the platelet, the lipid bilayer. What's the enzyme? And the answer is thromboxane synthase. Which drug prevents its formation? Aspirin. Does aspirin prevent the formation of thromboxane A2 reversibly or irreversibly? And the answer is irreversibly. What's the mechanism of action of aspirin? It inhibits cyclooxygenase. How long does it take after stopping aspirin for platelets to function normally again? And the answer is 48 hours. How about non-steroidals, not aspirin, other non-steroidals? First, is it reversible or irreversible for the non-steroidals? It's reversible. Okay, and how many hours after stopping them? 12 to 24. That's why aspirin is a very potent antiplatelet drug, at least as a load; that's why we call it baby aspirin. But don't give aspirin for babies because it can cause Reye's syndrome and destroy their liver. Baby aspirin means small dose for grandpa.
So we are done with thromboxane A2. Next, we have the tissue factor, also known as tissue thromboplastin or TPL, stored in the tissue—or really, it's called tissue factor, and the factor in the tissue—okay, released during tissue injury. After you injure the tissue, the tissue factor comes in contact with the blood, and it starts the extrinsic pathway by activating the crazy factor VII. VII is now active, and it's going to activate factor X into Xa and common pathway. You know the rest of the story.
Next, we have the crazy subendothelial collagen. It promotes platelet adhesion to the von Willebrand factor. This is primary hemostasis, and it starts the intrinsic pathway. This is secondary hemostasis by activating factor XII, also known as the Hageman factor.
Next here, we have the von Willebrand factor. Let's play the same game: questions and answers. Pause.
Okay, welcome back. Who makes the von Willebrand factor? The answer is the endothelial cells. Be specific, please. The Weibel-Palade bodies. Ooh, okay. These are bodies inside the endothelial cells; they make this von Willebrand factor. Where else is it found? It's found in the endothelial cells—oh, no kidding—and the platelets. Oh, really? Yeah, it's part of the alpha granules, the protein granules in the platelets. What's the function of this von Willebrand factor? First, platelet adhesion. What's the receptor? Glycoprotein Ib. And also, it binds factor VIII in the circulation, forming a complex. Then thrombin activates factor VIII into factor VIIIa. Common pathway, on fibrin, boom. And here is the $63,000 note: That's why, in cases of von Willebrand disease, when you don't have the von Willebrand factor, you have a primary hemostasis defect and a secondary hemostasis defect. That's why your bleeding time will be prolonged, and your PTT will be prolonged as well, because factor VIII cannot be activated without the von Willebrand factor. That's why we have von Willebrand disease: both primary hemostasis and secondary hemostasis are gone; both the bleeding time and the PTT are prolonged. This is very important.
Do you want another question? How to differentiate between hemophilia A, which is a defect in factor VIII, and von Willebrand disease, only by using lab? The answer is bleeding time, because both hemophilia A and von Willebrand disease prolong the PTT, but only the von Willebrand disease prolongs the bleeding time, and this is very important.
What are other procoagulant stuff? Platelets. Oh yeah, they are called thrombocytes. Activated endothelium. Remember, endothelium has a bipolar disorder. Under normal conditions, it's smooth; it's anticoagulation. But once there is an injury, it's activated, and it acts in harmony with platelets towards a common goal, which is clotting and coagulation. When the endothelium is active, it secretes endothelin, the protein of the endothelium, and this is procoagulation big time. And, of course, the coagulation factors of the intrinsic, extrinsic, and the common pathway, as well as factor XIII. Who secretes the coagulation factors? Answer: liver. What kind of stuff are they? Are they carbohydrate, proteins, or lipids? The answer is proteins. What kind of protein are they? Albumin or globulin? They are globulin. What kind of globulin are they? Are they alpha-globulin or beta-globulin? The answer is they are beta-globulin. How about gamma globulins? No, those are the immunoglobulins or the antibodies, but the coagulation factors are beta.
Baby quick review over the arachidonic acid pathway: We start with membrane phospholipid. Now we have the oxygenated by the cyclooxygenase. We have the prostaglandins. If you are in the platelets, that's formed thromboxane A2. If you are in the endothelium, it's formed prostaglandin I2, also known as prostacyclin. They are opposites, but they have the same origin; they come from the membrane phospholipid of the endothelium or the platelets, depending on the case. The platelets form thromboxane A2 to vasoconstrict and increase platelet aggregation. The endothelium forms prostaglandin I2, prostacyclin, to keep the blood cyclin by vasodilation and prevent platelet aggregation. Between thromboxane A2 and prostaglandin I2, which one is more affected by aspirin? Aspirin is going to tarnish this; this is gone with aspirin; this, not so much. That's why you bleed under aspirin.
That's it for today. Thank you so much for watching. Don't forget to subscribe. Get all of my notes if you go to patreon.com/scishow. See you again until next time. Be safe, stay happy, and study hard. This is Medicosis Perfeccionista Ellis.