 Let's start by discussing our direct thrombin inhibitors. As we mentioned, this directly inhibits the activity of free and clot associated thrombin, which is also known as 2A. When we inhibit thrombin, we're going to inhibit the ability of fibrinogen to be cleaved into fibrin to further go down to our clotting cascade. We use this for situations including venous thromboembolism as well as atrial fibrillation. This helps keep us from forming clots in these situations to reduce the possibility of problems down the road. The adverse effects that we can see with direct thrombin inhibitors include bleeding. Obviously, that is what it is intended to do is to keep clotting from happening so we can have bleeding occurring. One great thing about the direct thrombin inhibitors is that they do not require any lab monitoring. Some of the other medications that we will discuss later do require us to monitor lab values to make sure that we are within a therapeutic range. It is noteworthy that direct thrombin inhibitors can be used when we have HIT, which is known as heparin-induced thrombocytopenia. So if we cannot use heparin, then we can use the direct thrombin inhibitors. And this specific instance is what helps us remember what the direct thrombin inhibitors are. Because when heparin is bad for the patient, we can use these direct thrombin inhibitors, which are bivalorudin, argotrobin, and dabigatrin, which use B, A, and D. Of note on these, dabigatrin is the only one that is an oral agent in these class. The other two must be given intravenous. Let's continue on and discuss heparin. Heparin is used to activate antithrombin. This will then decrease the action of our 2A or our thrombin and our factor 10A. So heparin comes in here and it has a positive effect on antithrombin, which will then decrease the conversion of 10 to 10A, which decreases the ability of thrombin or 2A to form. What do we use this for? Well, when we have a pulmonary embolism, we can use heparin. We can use heparin also when we have an acute coronary syndrome, a myocardium farsion, deep vein thrombosis. And one thing that heparin is very useful for is pregnancy. It has a very short half-life, so if we have to stop the anticoagulation, we can stop it and manage any issues that can be going with pregnancy. It also does not cross the placenta, which is very good for use in pregnancy. With heparin, we do want to check our PTT values to make sure that we are within a therapeutic range and not over or under anticoagulating. Side effects, once again, because this is an anticoagulant, we can see bleeding occurring. We can also see thrombocytopenia, which is what we mentioned previously, also known as heparin-induced thrombocytopenia, or HIT. We can see osteoporosis or drug-drug interactions with heparins. So what is heparin-induced thrombocytopenia? What's happening here is we're getting antibodies, specifically IgG antibodies, that are going against that heparin-bound platelet factor 4. Antibodies are coming in, binding to that heparin-platelet factor, and then they activate the platelets, leading to the consumption of platelets, which gives us a thrombosis, and then because the platelets are being consumed to make this clot, we then have a thrombocytopenia that follows. If we need to rapidly reverse heparin because of a major bleeding event, we can use an antidote for heparin, which is protamine sulfate. Protamine sulfate is a positively charged molecule that positively charged molecule binds strongly with that negatively charged heparin. One of the most commonly used heparins is going to be a low molecular weight heparin known as inoxaparin. This is also known by its brand name of lovinox. This specifically likes to work on factor 10a. One of the great things about the low molecular weight heparins is that they undergo renal clearance versus hepatic clearance for our unfractionated heparins, therefore they don't have any effect to the liver. But that does mean we need to pay attention to them in patients that do have a renal problem, so they are contraindicated in renal insufficiency. One further problem that we do have with low molecular weight heparins is that they're not easily reversible. So if we have an upcoming surgery or if there's trauma associated with a patient, then low molecular weight heparins like inoxaparin are contraindicated.