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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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May 9, 2013

An Anticoagulant Antidote

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Posted by Derek

Here's a drug-discovery problem that you don't often have to think about. The anticoagulant field is a huge one, with Plavix, warfarin, and plenty of others jostling for a share of a huge market (both for patients to take themselves, and for hospital use). The Factor Xa inhibitors are a recent entry into this area, with Bayer's Xarelto (rivaroxaban) as the key example so far.

But there's a problem with any Xa inhibitor: there's no antidote for them. Blood clotting therapies have a narrow window to work in - anything effective enough to be beneficial will be effective enough to be trouble under other circumstances. Anticoagulants need a corresponding way to cancel out their effects, in case of overdose or other trouble. (Vitamin K is the answer for warfarin). We don't often have to consider this issue, but it's a big one in this case.

Portola Therapeutics has developed a Factor Xa mimic that binds the inhibitors, and thus titrates their effects. They have their own Xa inhibitor coming along (bextrixaban), but if this protein makes it through, they'll have done the whole field a favor as well as themselves.

Comments (8) + TrackBacks (0) | Category: Cardiovascular Disease


1. Christophe Verlinde on May 9, 2013 12:50 PM writes...

In what stage of trials is Perosphere's PER977, aslo a fXa antidote?

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2. milkshake on May 9, 2013 1:23 PM writes...

one typical urgent anticoagulant antidote scenario is an older male injured in car/motocycle crash. Head traumas are particularly bad news for a patient on anticoagulants

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3. NoDrugsNoJobs on May 9, 2013 1:32 PM writes...

Really clever, wish I had thought of it!

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4. Nate on May 9, 2013 2:08 PM writes...

Small point, Plavix (well, it's active metabolite) is a P2Y12 inactivating antiplatelet drug

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5. oldnuke on May 9, 2013 2:18 PM writes...

I told my Doctor that I was taking myself off Plavix for exactly that concern -- when I cut myself shaving, it took over 15 minutes to stop bleeding. I starting taking one adult aspirin with breakfast in the morning -- haven't had any more strokes and I don't need a transfusion after fighting with my razor!

I don't want to think what would have happened if I had some major trauma then...

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6. luysii on May 9, 2013 6:32 PM writes...

Well, for people on comadin or heparin, fresh frozen plasma (no cells) usually does the trick when trauma occurs (if the doc knows people are on the drugs -- why you should have a bracelet on your wrist saying so). Fresh frozen plasma has tons of coagulation factors.

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7. a. nonymaus on May 10, 2013 10:40 AM writes...

Have Factor Xa inhibitors been tested for rodenticidal activity against warfarin-resistant rats?
On the flip side of this, are these anticoagulants hazardous to tigers or polar bears that happen to devour a tourist that has been taking them? Could be an interesting study for J. Irrep. Res.

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8. drrpm on May 10, 2013 11:04 AM writes...

The ability to reverse anticoagulants can be crucial during emergency surgery. Plavix is particularly despised due to its profound effect on platelet activity. Its far worse than aspirin. Coumadin and Heparin are relatively easy to handle. FFP and platelet transfusions are not exactly risk free either. These medication not only increase surgical risk but limit anesthetic techniques since neuraxial blocks are contraindicated and even more peripheral blocks are riskier.

This problem is much more common today since more people are taking anticoagulants for a variety of reasons. Lots of people are on them now after having coronary artery stents placed. A patient needs to take Plavix for a year after placement of a drug eluting stent. This causes problems if they need a surgical procedure in the following year.

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