Direct factor Xa inhibitors

And the ACT is a whole blood test of the intrinsic and common pathways that we use when the heparin levels are too high for the PTT to read accurately, such as during cardiopulmonary bypass.

Now, the two most important targets in this entire episode are factor Xa and thrombin, which is also activated factor two a.

Almost every anticoagulant that we're gonna talk about today hits one or both of these targets, so keep these two targets in your mind.

We're gonna start with unfractionated heparin.

Now, heparin doesn't work by itself.

It's going to bind to antithrombin, which is a naturally circulating inhibitor and is going to accelerate antithrombin's activity.

Now, heparin plus antithrombin inhibits thrombin and factor Xa along with factors nine, eleven, and twelve.

Now, unfractionated heparin has roughly equal activity against thrombin and Xa, about a one-to-one ratio.

How should clinicians think differently about these medications, Factor XI, Factor XIa inhibitors, compared to what they already are familiar with?

The most commonly used agents now are the direct oral anticoagulants, or the DOACs, and they target factor Xa or thrombin, which sit lower down on the coagulation cascade in the common pathway.

Factor XI is positioned in the intrinsic pathway, and it turns out that when there is hemostasis for the formation of a hemostatic plug, it's triggered by high concentrations of tissue factor that cause explosive 10A and thrombin generation and factor XI isn't very important.

In contrast with intravascular thrombosis, there's a little bit of tissue factor and for that clot to grow, there has to be feedback activation of factor XI.

And so a lot of it is just based on the level.

And so we would recommend a level typically after a couple of doses, um, in anti-Xa, and our goals for treatment are between point five and one, and then we titrate to achieve that goal.

So a lot of children end up far higher.

And then obviously in our children who have renal impairment, then they also require renal dosing, so they may have a little less than one per kilo.

And I heard the anti-Xa levels have to be gotten at a specific time.

We don't wanna mess that up.

Yes.