Wednesday, November 9, 2011

Pradaxa (dabigatran), a new oral anticoagulant drug: Good news and bad news


Pradaxa (dabigatran) is a new oral anticoagulant that has many advantages over Coumadin (warfarin). Unlike Coumadin, Pradaxa is a direct thrombin inhibitor. Pradaxa is much easier to use. It does not require checking of clotting studies, nor are dietary restrictions necessary. That’s the good news.

Here’s the bad news. Unlike Coumadin, which can be reversed in an emergency with fresh frozen plasma (FFP) within a few hours and vitamin K within about 24 hours, there is no known way to reverse Pradaxa. If a patient who is taking Pradaxa presents with say, severe trauma or a perforated duodenal ulcer, what is an emergency physician or surgeon to do?

My colleague, Michael McGonigal MD, who blogs at Trauma Pro, posted a guideline on the emergency care of bleeding in patients on Pradaxa issued by the Institute for Clinical Systems Improvement (ISCI). A nice algorithm appears on page 2. It suggests holding the drug as step #1. [That is obvious.] Lab tests such as PT, INR, PTT and thrombin time are recommended with the caveat that they do not accurately reflect the bleeding risk or level of Pradaxa in the blood. Activated charcoal may be given if the drug was taken within two hours of arrival. FFP and vitamin K will not help as there is not a deficiency of clotting factors. Renal dialysis may be considered, but realistically, is it practical?

As a last resort, recombinant activated Factor VII (rFVIIa) or prothrombin complex concentrate (PCC) might be tried but get this: “The ICSI work group has included rFVIIa or PCC as options to help with clot formation at the site of bleeding. They do not reverse the drug, the correct dose is unknown, and there is no FDA approval for this use. Thrombosis is a known side effect of rFVIIa and PCC.”

The half-life of Pradaxa is 12-17 hours. Although the guideline does not address semi-emergency surgery, it might be wise in certain instances, such as in a patient with acute appendicitis, to wait at least 12 hours to perform the surgery. Keep in mind that laparoscopic surgery is usually done on patients with normal clotting. Unlike in open surgery, it is sometimes not possible to maintain a completely dry operative field when a laparoscopic procedure is done.

Unfortunately, the ICSI guideline is not very helpful. What it says to me is “Good luck if someone on Pradaxa comes in with head trauma or needs emergency surgery.” It’s not the ICSI’s fault. It seems like there is nothing one can do.

Since all I do is emergency surgery, I’m really looking forward to my first Pradaxa patient.

17 comments:

Gwynedd said...

Given that the time window for successful surgical intervention (meaning patient has reasonable chance of surviving and having meaningful neurological recovery) is one hour for acute epidural hematoma, and probably four, maybe six, depending, for acute subdural hematoma... Pradaxa is going to make a number of the family discussions re: risks and benefits of surgical intervention for acute SDH (which has vastly lower good outcome rates than epidural anyway) quite different.

Skeptical Scalpel said...

Agree. This drug is going to cause surgeons some problems.

Anonymous said...

I admitted a patient in September with intracerebral hemorrhage due to a head injury. He had been taking Pradax to decrease risk of stroke due to a fib. Instead he died of ICH. The company has to come up with an antidote soon. It is not going to help matters that people who have borderline renal function are getting started on it, meaning that the guidelines for how long to wait to operate will not be applicable.

Skeptical Scalpel said...

@Anonymous

Thanks for the comment. It seems your experience with Pradaxa was as I predicted. It could be rough going as more patients are transitioned from Coumadin.

Anonymous said...

I believe Pradaxa can cause shortness of breath. It can also cause a slight oder coming from ones body.

Skeptical Scalpel said...

Thanks for the comment. Do you have a reference for those two side effects? If so, please let me know.

Anonymous said...

I am 46 and was excited to switch over due to the "positive benefits". I'm nownc considering switching back

Skeptical Scalpel said...

I hope you didn't decide that strictly based on my blog.

Anonymous said...

checking INR is a way to monitor compliance. when you are using pradaxa, you lost this control.

Anonymous said...

Hello Skeptical Scalpel,
I'm a medical scientist working in a Haematology Dept in Brisbane, Australia. I am giving a presentation on "new oral anticoagulants (NOACs)- what monitoring if any?". As a result I have been trawling the internet & came across you website. I have since read a number of your blogs and find them very informative!
I wondered whether you have had your first "pradaxa" patient yet? or whether you know of many adverse events?

Skeptical Scalpel said...

Luckily, I haven't had a Pradaxa patient yet.

Here are two items from the New England Journal of Medicine about bleeding.
Http://www.nejm.org/doi/full/10.1056/NEJMc1112874
http://www.nejm.org/doi/full/10.1056/NEJMc1111095

Here's one from Arch Int Med about MI.
http://archinte.ama-assn.org/cgi/content/abstract/172/5/397

There are many more.

pradaxa lawyers said...

Symptoms of bleeding, one of the many adverse Pradaxa® side effects preceded many of the deaths linked to this anticoagulant drug. The FDA said it will be conducting the investigation to determine if the incidence of bleeding and deaths among patients prescribed Pradaxa® is higher than what would be expected based on observations in the clinical trial that was held before the FDA approved Pradaxa® (dabigatran).

Skeptical Scalpel said...

Thanks for the comment. You guys might see a lot more business.

Anonymous said...

I find it hard to believe that someone thought it was a good idea to create an anticoagulant that cannot be reversed...but I'm a neurosurgeon confronting my first trauma patient on Pradaxa, and I guess my perspective is skewed.

Skeptical Scalpel said...

Anonymous, I agree. On 11/2/2012, The FDA reaffirmed its approval of Pradaxa and said bleeding was no worse than that seen with warfarin. Here's the link: http://www.fda.gov/Drugs/DrugSafety/ucm326580.htm.

Anonymous said...

I am suppose to have a cataract operation on March 20/2013. I have been taking 150 mg of Pradaxa twice daily since August. I understand there is some risk of bleeding with cataract operations (although rare) and I am now wondering if I should go off this drug prior to the operation. I asked the eye surgeon and she said "Not necessary -- should not be a problem! I am not quite satisfied with that answer only because it is such a new drug that we don't know what the track record will reveal. It is disconcerting knowing that if you are on it and there is a bleed ... there is no reversal (as I understand it) ...

Does anyone out there have any suggestions.

Skeptical Scalpel said...

Disclaimer: I am not an eye surgeon, you are not my patient and this should not be construed as medical advice.

If you google Pradaxa and cataract surgery, you will find that unless you have some unusual circumstances like bleeding during previous cataract surgery, you should follow the advice of your eye surgeon. I suggest you share your concerns about this with her.

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