the coagulation cascade is one of those topics that you learn forget and relearn countless times during your time in medical school it's not uncommon to forget which factors apart the intrinsic or extrinsic pathways which test is used to assess each one or even where in the pathway different drugs act I'm going to put these together in one place and show you some tricks to remember particular bits so this is the skeleton to the coagulation cascade I'll draw the intrinsic pathway in red it results from contact activation whether is surface damage and features factors 12:11 nine and eight the extrinsic pathway is here in blue and it results from trauma or inflammation that leads to tissue factor release remember also that tissue factor is also known as factor three tissue factor and activated factor seven former complex together that can then activate factor ten as you can see the factor seven and tissue factor complex as well as factor eight both activate factor ten and this is therefore where both pathways meet and become the common pathway shown in purple activated factor ten causes prothrombin to become active thrombin known as factor two which then Cleaves fibrinogen into fibrin also known as factor one and ultimately leads to clot formation as a sidenote factor five is a cofactor or the other factors are enzymatically active an activated factor five is needed alongside calcium in order for activated factor ten to convert prothrombin into thrombin the way i remember which factors are in the intrinsic pathway and which are extrinsic is by thinking of when they do count dens for example they say count down in three two one but this time we remember that the count down is in the intrinsic pathway twelve eleven nine eight another way is that the extrinsic pathway contains factors 7 and 3 which is tissue factor and so they sum up to 10 which is also written as an X it's a bit of a stretch but it helps me remember them as for the lab tests a PTT is the activated thrombin just in time also referred to as PTT while PT is the prothrombin time the way to remember which test looks at which pathway is by remembering that you play table tennis inside while you play tennis outside remember the PTT and Pt tests also evaluate the common pathway to so factors 10 5 2 & 1 the PTT is normally 25 to 29 seconds while the PT is usually about 12 seconds but these values change between labs another important thing to remember is the vitamin K dependent factors which are factors 2 7 9 and 10 so causes for a prolonged PTT time with a normal PT included deficiency in factor 8 for example in haemophilia a or von Willebrand's disease a deficiency in factor 9 seen in haemophilia B or deficiencies in fact is 11 or 12 a prolonged PT with a normal PTT can come from factor 7 deficiency it may also be a sign of incoming disseminated intravascular coagulation or an early sign of vitamin K antagonism since factor 7 is the fact that we the shortest half-life this means that in the early stages the remaining vitamin K dependent factors which are 2 9 and 10 are not affected as much if both the PT and PTT are prolonged then causes include decreased vitamin K activity that's a more developed so again a vitamin K deficiency from a lack of intake or excessive warfarin treatment as well as this moderate to severe disseminated intravascular coagulation or liver disease may also be causes treatment with high doses of heparin or direct oral anticoagulant drugs can also cause a prolonged PT and PTT drugs used to prevent clotting act on different locations on this pathway heparin works by binding to antithrombin 3 and increasing antithrombin 3 activity which works to inhibit activated factor 10 and thrombin low molecular weight heparins like an ox apparent and delta Perrin work in a similar way but the antithrombin 3 low molecular weight heparin complex has less or no activity against thrombin while having a more specific affinity for activated factor 10 warfarin is a vitamin k reductase inhibitor and vitamin k reductase is needed to restore bitman k back to its activated state if this can't happen then no activated vitamin k is available to form the vitamin k dependent factors and so less of these factors are synthesized it takes time however for the amount of activated vitamin k to decrease significantly and therefore for synthesis to stop so this is why patients often a given heparin for a few days while waiting for the warfarin to work in fact warfarin actually promotes clotting in the first few days because it also inhibits protein c and protein s which anticoagulant molecules involved in inhibiting factor v the direct oral anticoagulants dough acts sometimes called no acts work by directly binding thrombin or activated factor 10 rivaroxaban and apixaban for examples of direct activated factor 10 inhibitors while a caravan and Dhoby Ghaut run her examples of direct thrombin inhibitors you can see this difference in the name with rivaroxaban for example featuring factor 10 a ban in the name the effects of heparin can be reversed with protamine sulfate a compound that binds tightly to the heparin or the low molecular weight heparin forming a compound with no anticoagulant properties the antidote to warfarin is vitamin k but just as warfarin takes time to work the antidote also takes a while because new factors need to be synthesized fresh frozen plasma and prothrombin complex concentrate may be given for immediate reversal but you still need vitamin K to maintain it I broke a zoom up a monoclonal antibody is given as an antidote for Davy Katrin while an excellent alpha was recently approved as an antidote for the direct practice 10 inhibitors you [Music]