 This video will cover the following objective from Physiology of Blood, Hematology. Define and describe the mechanism of hemostasis. Describe the stages involved in the coagulation process, including the intrinsic and extrinsic clotting pathways. Define thrombus, embolus, embolism, and hemophilia. Injury to a blood vessel initiates the process of hemostasis, which involves three steps, a vascular spasm, platelet plug formation, and coagulation. In the first step, the ruptured blood vessel wall stimulates endothelial cells in the inner lining of the blood vessel wall to release a paracrine signal known as endothelin, which stimulates the vascular smooth muscle to contract. This vasoconstriction increases resistance and decreases blood flow, helping to slow the rate of blood loss. In the next step, activated platelets start to stick together and bind to the exposed collagen in the damaged blood vessel wall. As the platelets become activated, they release chemical signals that stimulate more platelets to become activated and a positive feedback mechanism until a platelet plug forms to stop the bleeding. Step three is coagulation, where the protein in the plasma called fibrinogen becomes fibrin and forms a network of fibrous protein in order to help reinforce the platelet plug, stabilize the blood clot. The process of coagulation can be initiated by either an intrinsic pathway or an extrinsic pathway, where clotting factors become activated, leading to the formation of the fibrin crosslinked blood clot. The intrinsic pathway is initiated when factor 12, also known as the Hageman factor, is activated by exposed collagen in the damaged blood vessel wall. Then factor 12 will activate a cascade of other clotting factors. Factor 12 activates factor 11 and then factor 11 activates factor 9 and then factor 9. Together with factor 8 will stimulate the factor 10. Factor 10 is also known as thrombokinase and is the beginning of a final common pathway and so we'll see both the intrinsic and the extrinsic pathway converge on the final common pathway. So the extrinsic pathway is stimulated by a clotting factor from outside of the blood vessel. This is known as factor 3, so factor 3 is also known as tissue factor or thrombo-plastin, but factor 3 comes from a damaged tissue outside of the blood vessel and then diffuses into the blood vessel where it will then stimulate another clotting factor known as factor 7 and factor 3 and 7 together activate thrombokinase factor 10 to initiate the final common pathway of coagulation. So the final pathway, the common pathway of coagulation starts with the activation of factor 10 thrombokinase which then stimulates the conversion of pro thrombin into thrombin. So pro thrombin is an inactive form of clotting factor number 2. Factor number 2 becomes activated to form the active thrombin and then thrombin converts fibrinogen into fibrin so that fibrin can form an insoluble cross-linked network to stabilize the blood clot. And so you'll notice that these clotting factors are all numbered. There are 12 different clotting factors numbered 1 through 13, so 12 factors 1 through 13. We don't have a clotting factor number 6, so number 6 is no longer a distinct factor. It was previously believed to be a clotting factor and then later we discovered that clotting factor was the same as another factor. So there are clotting factors that are numbered in the order they were discovered, but not in the order that they become activated in the mechanism of coagulation. Another clotting factor that is essential for the coagulation mechanism is calcium. So calcium, which is also known as clotting factor number 4, is required for activation of other clotting factors. Similarly, there's a vitamin that's required for the mechanism of coagulation. Vitamin K is necessary for the production of many of the clotting factors and so vitamin K is required for blood clotting. And this is important because there's medications that are used in order to decrease blood clotting, which are inhibiting the metabolism of vitamin K. So warfarin is an example or kumadin is an example of a drug that inhibits vitamin K metabolism in order to prevent blood clotting. When a clot forms inside of an intact blood vessel, this is known as a thrombus. And so you can see the word thrombo site and thrombus are closely related, referring to a blood clot. A thrombus is specifically a blood clot forming inside of an intact blood vessel. If a thrombus breaks loose and starts to travel in the blood, that's what we call an embolus. And an embolus is dangerous because this blood clot traveling through the circulation can then get lodged into a small blood vessel and block blood flow into a tissue, which is what's known as an embolism. And so if an embolism blocks a blood vessel in the heart, if it blocks a coronary artery, this could cause a heart attack. Or if an embolism were to block a artery supplying blood to the brain, it could cause a stroke. One of the most common types of embolisms is a pulmonary embolism. So an embolism could result from a blood clot forming inside of a vein, and this is more commonly associated with long periods of inactivity. For example, sitting on an airplane for a long period of time is one of the things that's commonly associated with increased risk of an embolism. It has the blood clot forms inside of the pooling blood inside of the veins. That blood clot creates an embolus that travels through the veins into the heart, and then those veins are large enough to carry the embolus, and the heart can then pump the embolus out into the arteries, and it will be pumped from the right ventricle out into the pulmonary arteries, and the embolus will be carried into smaller and smaller arteries in the pulmonary circuit until it gets lodged in a small pulmonary artery branch forming an embolism that cuts off the blood flow to that region of the lung, and this would then disrupt gas exchange, linked to shortness of breath, producing other symptoms as a result of disruption of the gas exchange in that region of the lung. After the formation of a blood clot, fibrinolysis is the mechanism that breaks down fibrin in order to remove the blood clot. The enzyme plasmin binds to fibrin and catalyzes hydrolysis of the fibrin in order to produce short peptides, also known as fibrin degradation products. So plasmin is circulating as an inactive precursor, plasminogen. Plasminogen binds to fibrin and then another signal known as tissue plasminogen activator stimulates the conversion of plasminogen into the active enzyme plasmin. This is important because we take advantage of this mechanism medically with a drug known as a clot blood, a clot buster. A clot buster is an injection of tissue plasminogen activator which stimulates the process of fibrinolysis, and so a clot buster could be used in order to intervene in a stroke or heart attack or other kind of embolism in order to break up the clot and restore blood flow to the tissue that has been cut off by a blood clot. Hemophilia is a clotting disorder that results from deficiency of a clotting factor which leads to excessive bleeding. The most common forms of hemophilia are hemophilia A and hemophilia B. Hemophilia A results from deficiency of factor 8 and hemophilia results from deficiency of factor 9. So factor 8 and factor 9 were the clotting factors that become activated downstream from factor 12 in the intrinsic blood clotting pathway. Hemophilia is more common among males than females. This is because the genes for factor 8 and 9 are found on the X chromosome. So if a woman has one mutation in a clotting factor 8 or 9 gene, she may have another version of that gene in order to compensate for the loss of function mutation. However, if a male has just one copy of that gene and that copy is mutated to disrupt its function, that male will then have hemophilia as a result.