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An Update on Bleeding Problems with Dabigatran (Pradaxa)

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Updated December 27, 2012

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

Dabigatran (Pradaxa) is the first of a new family of anticoagulant drugs (blood thinners) being developed as an alternative to Coumadin (warfarin). Dabigatran, which has been on the market since 2010, is now being widely used instead of Coumadin to reduce the risk of stroke in people with atrial fibrillation. However, shortly after dabigatran was approved, concern developed because it began to appear as if bleeding problems with this new drug might be more severe than similar bleeding problems with Coumadin. Because anticoagulant drugs work by reducing the clotting of blood, any bleeding that occurs in patients taking these drugs tends to be difficult to control, and therefore tends to be relatively dangerous and may even be life-threatening. Bleeding problems with dabigatran can be especially difficult, because (unlike with Coumadin) there is no lab test that reliably helps the doctor assess the "thinness" of the blood in patients taking dabigatran, and (also unlike with Coumadin) there is no drug that can be given to rapidly reverse the effect of dabigatran. Recent evidence, however, now suggests that bleeding problems with dabigatran might not be as severe as previously feared.

Advantages of Dabigatran Over Coumadin

Even with the questions regarding its relative safety, dabigatran has proven to be a compelling choice for many patients with atrial fibrillation. This is because the safe use of Coumadin is inconvenient, logistically difficult, and often frustrating for both doctors and patients. Using Coumadin safely always requires frequent blood tests and dosage adjustments, often for weeks or months - and periodic testing and adjusting thereafter. All too often, a dosage of Coumadin that had previously seemed optimal will turn out a few months later to be too high (increasing the bleeding risk) or too low (increasing the stroke risk).

In contrast, a standard daily dose of dabigatran appears to provide just the right amount of anticoagulation in virtually everyone, without any blood testing or dosage adustments.

So, despite the concern that has developed over the potential difficulty in controlling bleeding episodes in patients taking dabigatran, it has become the treatment of choice for many patients who need anticoagulation due to atrial fibrillation.

What Is the Status of Treating Bleeding Problems With Dabigatran?

Here is what UpToDate, an electronic reference for doctors and patients, has to say about treating bleeding events that occur on dabigatran:

"There is no antidote for dabigatran. Although clinical data are generally lacking, suggestions for reversing its anticoagulant effect have included the following:
  • Drug discontinuation is usually sufficient to control bleeding in most clinical settings, since its half-life is relatively short (12 to 14 hours) in subjects with normal renal function.
  • Dabigatran is about one-third protein bound. It can be dialyzed in patients with renal impairment, with about 60 percent being removed after two to three hours of dialysis.
  • Other drugs that may potentiate bleeding should be discontinued, if possible.
  • Use of activated charcoal may remove unabsorbed drug from the gastrointestinal tract if given within two hours of ingestion."
To summarize, the treatment of bleeding problems in patients on dabigatran is limited to managing the bleeding as best as one can until the drug leaves the system (usually within 24 - 48 hours), and using activated charcoal to inhibit absorption of the drug from the gastrointestinal system. People with kidney failure can be treated with dialysis. (Dabigatran is excreted through the kidneys.) Of note, the experts at UpToDate have concluded that the use of PCC (a combination of blood clotting factors that is given intravenously), a treatment for which they previously held out hope, now appears to be unhelpful in reversing the effects of dabigatran.

What Is the Latest On Bleeding Problems With Dabigatran?

In December, 2012, at the American Society of Hematology 2012 Annual Meeting, investigators from McMaster University presented the results of a major new study on bleeding problems with dabigatran. They assessed the outcomes in patients enrolled in five major clinical trials who had bleeding problems while taking either dabigatran or Coumadin - a total of 1034 major bleeding episodes among 26,000 enrolled patients.

They concluded that the mortality rate at 30 days was lower among patients with major bleeds on dabigatran, as compared to patients with major bleeds on Coumadin. There were also fewer days spent in intensive care among patients on dabigatran, and fewer of them required surgery to attempt to control the bleeding.

So, despite the lack of a method of rapidly reversing the anticoagulant effect of dabigatran, major bleeding episodes on this drug appear to have outcomes that are no worse than similar episodes on Coumadin.

Summary

There are significant risks to taking any anticoagulant drug. The reason anticoagulants are important in patients with atrial fibrillation is that the risk of stroke far outweighs the risks caused by blood thinners.

Dabigatran certainly has proved to be an attractive alternative to Coumandin for many patients with atrial fibrillation. However, the inability to rapidly reverse the effects of dabigatran during a major bleeding episode has dampened the enthusiasm for this drug. The latest data from McMaster University should mitigate some of this concern - but the fact remains that if serious bleeding should occur on dabigatran (or for that matter on any anticoagulant), at best the doctor and patient are faced with a very difficult problem.

In the future, this issue is likely to be mitigated by a drug that will rapidly reverse the effect of dabigatran. Boehringer Ingelheim (the company that makes dabigatran) has developed such a drug, and at this date it is in early clinical trials.

Want to learn more? See UpToDate's topic, "Atrial Fibrillation" for additional in-depth medical information on the importance of anticoagulation in atrial fibrillation.

Sources:

Leung LLK, Mannucci PM. Anticoagulants other than heparin and warfarin. UpToDate. Accessed: December, 2012.

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