Stop the bleeding!

As emergency physicians, we know how to handle bleeding. But what about when the patient is on anticoagulants? Last week our ED pharmacist, Gary Peksa, PharmD, gave us some advice on how to stop the bleeding in a patient on anticoagulants. Here is a brief overview on what he taught us. Let’s start by discussing all the intricacies of the coagulation cascade and how each of the anticoagulants work:

Just kidding. But you should at least be familiar with how these medications work in order to know how to appropriately reverse them in cases of major bleeding (at Rush, defined as hypotension resistant to fluid resuscitation and requiring vasopressor therapy) or in cases of urgent invasive procedures.

By far the most commonly used anticoagulant is warfarin (Coumadin), a vitamin K antagonist. Here are our current recommendations for warfarin reversal:

In a non-bleeding patient:

  • INR < 4.5: Do nothing, simply hold the warfarin
  • INR 4.5-10: May consider vitamin K (phytonadione) 2.5mg po x1
  • INR > 10: vitamin K 2.5-5mg po x1

In a bleeding patient with INR >1.4:

  • Non-emergent:
    • FFP 10-15mL/kg
    • Vitamin K 5-10mg IVPB
  • Life threatening hemorrhage or unstable patient:
    • PCC based on INR and weight
    • Vitamin K 10mg IVPB

 

One of the downsides to using FFP is the large volume (be cautious in heart failure, ESRD patients, etc.). PCC, on the other hand, is less volume. There are actually several different types of PCC, which can be made up of different factors. At Rush we carry 4 factor PCC (Kcentra) which replaces clotting factors II, VII, IX and X.

One of the benefits of warfarin is that we can easily monitor the response to anticoagulant reversal by checking a patient’s INR. But what about patients on direct oral anticoagulants (DOACs)? These are a bit trickier as we don’t have readily available lab tests that we can use to monitor these and guide reversal.

Three of the most commonly used DOACs are dabigatran (Pradaxa), rivaroxaban (Xarelto) and apixaban (Eliquis). When a patient needs one of these DOACs reversed, the first thing you need to do is discontinue the drug. If the patient has taken the DOAC in the past 2 hours, you can additionally give activated charcoal to prevent further absorption of the medication.

To reverse the effect of the drug that has already been absorbed, you have a few options: using PCC (such as Kcentra) or one of the newer reversal agents. Hemodialysis is also an option, but hemodialysis will only work for dabigatran. Here is a brief overview of the reversal agents that are currently FDA approved:

Idaricizumab (Praxbind):

This is a reversal agent for dabigatran (Pradaxa). This is a humanized antibody fragment with a 350 fold higher affinity for dabigatran than dabigatran for thrombin, neutralizing the drug. Once the drug is neutralized, endogenous factors should then work to attain hemostasis.

Andexanet alfa

This is a decoy of factor Xa, used to reverse Xa inhibitors such as apixaban (Eliquis) and rivaroxaban (Xarelto). Again, given that it is a decoy of factor Xa, it is a direct reversal of the drug but we must still rely on endogenous factors to achieve hemostasis. Additionally, andexanet alfa, given as an infusion, is very short acting (half-life about 1 hour) and there is a risk of rebound anticoagulation after it is discontinued. There is some debate on this reversal agent as the original study on this drug did not include a comparator group (feel free to speak to your local ED pharmacist for their opinion on this!). Additionally it is quite expensive and we currently do not have this as a treatment option in our ED. Our preferred treatment at Rush is presently off-label use of PCC for reversal of factor Xa inhibitors. But you may see andexanet alfa used in the future.

 

For a quick reference, here is a guideline for reversal of major bleeding or urgent invasive procedure:

 

Thanks again to Gary Peska for this awesome lecture!

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