New Developments in Reversing Anticoagulation

Hans-Christoph Diener, MD, PhD


September 10, 2015

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I am Christoph Diener, a stroke neurologist from the University Hospital of Essen in Germany. Today's topic is reversal of anticoagulation—in particular, warfarin and dabigatran in patients who either have major bleeding or have to undergo surgical procedures. There are three recent publications that cover this topic.

The first study, by Parry-Jones and colleagues,[1] is an analysis evaluating treatment of 1547 patients from nine countries who had warfarin-induced intracerebral hemorrhage.Overall, 24% of these patients received fresh frozen plasma (FFP) alone, 38% received prothrombin complex concentrate (PCC) alone, 9% received both FFP and PCC, and 29% did not receive FFP or PCC. They looked at crude case fatality in each of these groups, which was 62% among patients not receiving FFP or PCC, 46% among patients receiving FFP alone, 37% among patients receiving PCC alone, and 28% among patients receiving both FFP and PCC. These results indicate that the most effective therapy for warfarin-induced cerebral bleeding might be the combination of PCC and FFP. However, the problem with FFP is its volume effect, and it cannot be given to patients who have kidney problems.

The next study looked at the reversal of the activity of warfarin in patients who had to undergo urgent surgery or an invasive procedure. In this randomized controlled trial from Goldstein and colleagues,[2] 181 patients were randomized to receive 4-factor PCC or FFP.Normalization of hemostasis was achieved in 90% of patients receiving 4-factor PCC and in 75% of patients receiving FFP. On the basis of these results, I think there is a clear indication that 4-factor PCC is superior to FFP for these patients.

I think this last study is the most important one. Pollack and colleagues[3] reported preliminary results for a specific antidote for dabigatran called idarucizumab.In this prospective cohort study, there were 90 patients in two groups: major bleeding or undergoing urgent surgery. All of these patients received two infusions of 2.5 g idarucizumab. Among most patients, coagulation parameters were normalized within 10 minutes. I think the most important result is from the patients who had to undergo surgery, because with the exception of one patient, none had major bleeding. These findings are highly relevant because it would really change the whole game plan if we had a specific antidote for dabigatran available in our emergency rooms.

We now have good evidence that PCC is more effective than FFP, both in the treatment of intracerebral hemorrhage and in antagonizing the effect of warfarin. In addition, we have evidence for a highly specific antidote for dabigatran, and I hope that this will be approved in the near future.

Thank you very much for listening. I am Christoph Diener, a stroke neurologist from the University of Essen in Germany.


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