00:01 Okay, let's talk now on the flip side. 00:04 We've talked about bleeding disorders. 00:06 Let's turn to thrombotic disorders or hypercoagulability, also, called, “Thrombophilia,” meaning, “Loving tooth thrombose.” What leads to a thrombus? This is a very important concept, again, Virchow, our good German pathologist, who was kind of the father of pathology. 00:25 Identified kind of a triad, the things that will contribute to driving thrombosis. 00:32 And there are three components to it hence the triad. 00:35 Number one is probably going to be endothelial injury and that makes a lot of sense because endothelium is going to be really, really important, in terms of driving, both coagulation, but also, anticoagulation. 00:47 And if the endothelium is not happy, you're going to have a tendency to be more pro-thrombotic. 00:52 So, endothelium is one angle of the triangle of the Virchow’s triad. 01:00 Another one, is “Stasis” or “Turbulence,” so, basically, abnormal flow. 01:04 If you have blood sitting around for a period of time, you will get stochastic activation of coagulation factors and you'll form a clot. 01:11 If you have turbulence, that's actually on the backside of turbulence, you'll have eddy currents, so that you will have focal areas of stasis. 01:20 So, abnormal flow, non-laminar flow, is also going to be something that will lead into thrombosis. 01:27 And the final component of the triad is, “Hypercoagulability.” And this is much more than kind of a general concept, there are a number of things that we'll talk about shortly, that lead to a greater tendency to have thrombosis. 01:42 You make more coagulation factors, you make less anticoagulation factors, you activate coagulation inappropriately, all of these things will contribute to thrombosis. 01:55 Now, it's not just those three things in isolation, but they all crosstalk with one another. 02:00 So, endothelial injury, actually, because it's important for driving both, coagulation and anticoagulation, will lead to hypercoagulability. 02:08 An endothelial injury, clearly will lead to areas of stasis or turbulence. 02:13 And stasis or turbulence in turn will impact endothelial integrity, so, all these things crosstalk. 02:21 But in general, when we have a thrombus, one or more of Virchow’s triad has been in play. 02:29 So, endothelial injury, is going to be a major driver for arterial thrombi and it's mostly platelet-driven. 02:37 Keep in mind, as we talk about clotting that occurs anywhere in the vascular system, if there's a lot of flow, it's going to be very hard for coagulation factors alone to drive a thrombus, because they're going to be diluted, they're going to be driven downstream very quickly. 02:54 So, in the arterial circulation, if a thrombus occurs, it's usually because we've had endothelial injury and we've recruited platelets that can stick quite firmly, quite avidly to the underlying von Willebrand factor for example. 03:09 So, arterial thrombi, tend to be due to endothelial injury and are platelet-driven. 03:15 Conversely, where there's stasis, now we can have local activation of the coagulation factors and so, in venous thrombi, it's usually coagulation factor driven, not so much by platelets. 03:29 So, we don't have endothelial loss, we don't have exposure or underlying von Willebrand factor and so the venous thrombosis tends to be driven by coagulation factors. 03:44 Thromboembolism, let's just kind of look at a couple examples, three examples to be exact. 03:48 So, here we have a pulmonary embolus, the big inverted y-shaped white thing up top, is a pulmonary artery, that branches into the right and left pulmonary arteries and that defect in the whiteness, is a pulmonary embolization. 04:08 This occurred, almost certainly because of relative stasis, in the lower extremity veins and that could have been due to a variety of things, including just inactivity and then that thrombus that formed there, in the venous circulation, breaks free, goes through the heart and impacts in the pulmonary circulation. 04:31 So, that's a pulmonary embolism or a thromboembolism. 04:35 Now, we're on the arterial side. 04:37 So, that large circle near the top with the white defect. 04:42 That white defect is in fact the normal flow, we’ve put in a radio opaque dye, so that, we can see where the lumen is and there's a vast darker area around that. 04:53 That is an abdominal aortic aneurysm and the darker area, that is excluding the dye, is a big thrombus. 05:01 And it's occurring there, because we have abnormal flow, we have a dilated aorta, so, we can have relative areas of stasis and in that setting we are now getting a thrombus that forms. 05:15 We can also have, in the right ventricular chamber here, a thrombus indicated by the arrow that is forming, as a result of endothelial dysfunction. 05:24 So, we now have abnormal anticoagulation, regulatory effects occurring and we're getting a thrombus that's formed. 05:35 So, we have the three different components of Virchow’s triad. 05:39 On the pulmonary embolism, that's forming due to stasis. 05:42 We have abnormal flow in our aortic aneurysm. 05:46 And we've got abnormal endothelium and so all of these will be leading to thromboembolism.
The lecture Virchow's Triad – Thrombotic Disorders by Richard Mitchell, MD, PhD is from the course Hemostasis.
What will endothelial injury result in?
How does stasis of blood flow lead to thrombus formation?
What is a risk factor for pulmonary embolism?
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