hemostasis is divided into primary hemostasis which involves platelet plug formation and secondary hemostasis which is the coagulation cascade the classic coagulation cascade is divided into the extrinsic pathway and the intrinsic pathways both of which lead to what is called the common pathway the hallmark of both the extrinsic and intrinsic pathways of coagulation is the sequential activation of a series of clotting factors clotting factors are shown as roman numerals and numerals followed by the alphabet represent an active clotting factor for example factor 10 becomes factor 10a 10a being the active factor so let's focus on the extrinsic pathway following platelet plug formation tissue injury causes expression of tissue factor which together with factor 7a will activate many molecules of factor 10 to become factor 10a the intrinsic pathway is initiated by the exposure of blood to a negatively charged surface which activates factor 12. this in turn activates factor 11 9 and then 8. factor activated factor 8 will activate factor 10. the intrinsic and extrinsic pathways will activate factor 10. factor 10a and factor 5a make up the beginning of the common pathway factor 10a and 5a as the cofactor activates prothrombin to become thrombin which is our factor 2a the active form thrombin which are the factor 2a molecules then convert fibrinogen to fibrin fibrin is factor 1a local generation of fibrin in turn in meshes and reinforces the platelet plug which was formed from the primary hemostasis bleeding is successfully stopped it is important to know that calcium is involved in the cotton cascade in a few steps so this is the classical view of the chlorine cascade based on the extrinsic and intrinsic pathways the classical view is very useful in interpreting coagulation tests and identifying bleeding disorders based on the coagulation factors however physiologically the coagulation cascade is much more confusing there is a cell-based model for coagulation which involves three main steps the first is initiation it is now believed the generation or exposure of tissue factor from the extrinsic pathway at the wound site and its interaction with factor 7 a is the primary physiological event in initiating clotting leading to activation of thrombin this small initial amount of thrombin generated then activates factor 5 11 and 8 in a feedback manner leading to amplification of thrombin generation interestingly and on a side note factor 8 is carried usually by von willebrand factor because it increases the factors half-life factor 2 a release is factor 8 from von willebrand factor in summary step 2 is amplification where the small amount of thrombin generated from the extrinsic pathway activates vector 5 8 and 11. this in turn activates the platelets activated platelets and the activated factors earlier then leads to the propagation step activated factors here form the intrinsic 10a resulting in factor 10a activation the activated factor 10 binds with factor 5a to form the pro-thrombinase complex pro-thrombinase complex converts rapidly prothrombin into thrombin directly onto platelets and subsequently forms fibrin so in summary that was the cell-based model initiation amplification and propagation and ultimately prothrombinase complex which forms a lot of thrombin and subsequently a fibrin mesh stopping bleeding to restore vessel patency following hemostasis the clot must be organized and removed this is called fibrinolysis fibrin gets broken down to fibrin degradation products including d-dimers by the enzyme plasmin plasmin is derived from its precursor plasminogen which is activated by plasminogen activator tpa interestingly thrombin activates a molecule called thrombin activatable fibrinolysis inhibitor and as the name suggests this inhibitor basically slows down fibrinolysis so you want to slow down the breakdown of the fibrin now that we know the classic model of the coagulation cascade which involves the intrinsic pathway and the extrinsic pathway and then we learned about the cell-based model which includes initiation amplification priming and propagation it is important to learn about the control mechanisms and the termination of the clot or coagulation the coagulation cascade involves interaction of the activated platelets and the clotting factors with its propagation of thrombin and fiber information is good to stop bleeding and commence healing however you can imagine if the coagulation cascade is continuous without a break a thrombus can form leading to clots in the veins the arteries causing organ damage the body thus has a few ways to stop and control clotting this is the antithrombotic pathway the first antithrombotic pathway to remember is protein c and protein s as clot formation progresses thrombin which is factor 2a binds to thrombomodulin an integral membrane protein on the endothelial cell surface the thrombin thrombomodulin complex activates protein c which with together with protein s as a cofactor inhibits factor 5a and factor 8a activity halting coagulation another antithrombotic pathway is through tissue factor pathway inhibitor or tfpi which circulates in plasma but at very low concentrations it works in the extrinsic pathway and inhibits factor 10 activation in two main ways it directly inhibits factor 10a and it inhibits tissue factor and fattening a the other antithrombotic pathway is the c1 esterase inhibitor c1 esterase inhibitors is a protease inhibitor and inhibits fact 11a 12a as well as the complement proteases c1r and c1s deficiencies of c1 esterase inhibitor results in in something called the hereditary angioedema the final antithrombotic pathway involves antithrombin a circulating protease inhibitor it neutralizes most of the enzymes in the cotton cascade inhibiting formation of thrombin factor 10a and 9a so those were the antithrombotic pathways which help control and terminate the cotton cascade or the coagulation cascade then you have fibrinolysis control mechanisms we already talked about thrombin activatable fibrinolysis inhibitor which slows fibrinolysis another mechanism to control fibrinolysis is through plasmin activator inhibitor pa i1 which inhibits tpa thus inhibiting plasmin formation again another one is also alpha2 antiplasmin which inhibits plasmin activity directly this means that fibrin is not broken down and you still have basically the clot being formed on a side note tranexamic acid is a medication that is used to stop bleeding by inhibiting tpa and preventing fibrinolysis so you want the clot to still be there you don't want it to break otherwise you can bleed easily so thank you for watching in summary we talked about the the classical coagulation cascade which includes the intrinsic and extrinsic pathway we also learned about the cell-based model which includes initiation amplification and propagation finally we talked about the control mechanisms of coagulation cascade as well as the control mechanisms of fibrinolysis [Music]