EP11: Reversing Anticoagulants - Warfarin Vs. NOACs


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Warrick is a practicing cardiologist and author with a passion for improving care by helping patients understand their hot health through education. Warrick believes educated patients get the best health care. Discover and understand the latest approaches and technology in heart care and how this might apply to you or someone you love. 
Hi, my name's Dr Warrick Bishop and I'd like to welcome you to my consulting room. Today, I'd like to speak with you about a conversation I've had with a number of patients in recent time. That conversation is about having a medication for anti-coagulation and having available for that medication, an anti-dote. There are two groups of anticoagulant that we use at the moment. Historically, and currently we've use Warfarin. Warfarin is a drug that works through the vitamin K dependent factors of the coagulation cascade. The newer group of agents, which we're going to call the NOACs, Novel Oral AntiCoagulants, work at precise locations within the calculation cascade. When it comes to reversing anticoagulation, the simplest way to do it is to just withhold the medication. With time, the body produces the factors involved in the coagulation cascade, and the system returns to normal. This can be a matter of days for most of those agents. 
In an emergency setting, if you've broken a leg, or if you're bleeding internally, or need urgent surgery and there's a requirement to reverse that anticoagulation urgently, particularly in a situation of severe hemorrhage, then one thing we can do regardless of whether it's Warfarin or one of the NOACs is take fresh frozen blood products and put those products which include the factors for coagulation into the patient so that it provides what's needed to stop bleeding and return the coagulations system or the clotting system back to normal. 
Some of my patients say look, I'd rather stay on Warfarin because we can use vitamin K as an antidote. Well, that is partly true but not fully correct. The reality is that vitamin K dependent factors take time to produce. So if someone does have bleeding problems with Warfarin and you give them Vitamin K to overcome the blocking effect of Warfarin to try and restore the coagulation system, then the liver actually has to produce those factors to have the system working again. Vitamin K dependent co-factors can take six hours or more to start being produced. So in the acute, very urgent setting of severe hemorrhage, that's just not quick enough and in that setting, the blood products injected into the blood stream do the job. In the situation of the NOACs, one of the agents, called the Dabigatran, has had a particular agent made, which, when it's injected into the body, binds with the Dabigatran and makes it inactive. This particular agent called Praxbind works almost immediately, and is an ideal solution in the setting of uncontrollable bleeding. 
There are two other NOACs - one called Rivaroxaban and one called a apixiban, and both of these agents have an antidote on the horizon called Andexinate.  Andexinate is not yet available in Australia. It is undergoing trials at the moment, and it does look promising, and if Andexinate does prove to be effective, then it will have a similar role in being able to be injected, and provided a decoy protein for absorbing these particular agents and restoring the coagulation system very rapidly. 
So, as much as it would be nice to think that there's an antidote for Warfarin, there sort of is but it doesn't work quickly enough to be effective. 
With regard to our NOACs, Dabigatran has Praxbind available, and this is a fantastic agent that really works. It is available in the Australia, and particularly in major centres. The other NOACs may well have an agent available in the next couple of years. In the meantime, if Praxbind is not available, and you're on Dabigatran or if you're on Warfarin or one of the other two NOACs, then injection of blood products to restore and replace the coagulation cascade is really the only option. 
I'm afraid Vitamin K is just not an adequate antidote for Warfarin reversal in the the acute setting, it can be helpful however in some less urgent situations. 
Little bit of a complex subject, hope it makes some sense and I hope you enjoyed it. Thank you so much for listening and I wish you the very best. Thank you. 
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