The package insert for dabigatran recommends emergency dialysis as a reversal strategy, stating that about 60% of dabigatran is removed over 2-3 hours. "This [strategy] may work," said Dr. Cipolle, observing that about 80% of dabigatran is renally excreted, compared with 66% of rivaroxaban and only 25% of apixaban.
Although not trivial, the half-lives of dabigatran (14-17 hours), rivaroxaban (9 hours), and apixaban (9-14 hours) are shorter than that of warfarin (40 hours), which means that "if you can wait and just not give them the drug, you are probably going to be okay," he said.
Dr. Cipolle cautioned, however, that reversal of labs may not indicate loss of anticoagulant effects. Also, clotting factors and continued prolongation of anticoagulation assays do not indicate lack of effect.
"The drug industry has spent years developing a drug that we could take orally that you don’t have to measure, and all we want to do is measure it," he said. "We would like to know just how much anticoagulant effect is present, and if our reversal strategies are working.
"A normal PTT [partial thromboplastin time] is very helpful, but other than that, the classic anticoagulation studies aren’t terribly helpful."
This point was also referenced in a recent letter to the New England Journal of Medicine penned by two trauma surgeons and an emergency physician who treated several injured patients on dabigatran, all of whom had poor outcomes (N. Engl. J. Med. 2011;365:2039-40). Although their values for activated clotting time on rapid thromboelastography (rTEG) were grossly abnormal at the time of admission, all of the patients had normal results on conventional anticoagulation studies.
"Unfortunately, even with the aid of rTEG, supportive care is all that is available in the emergency setting," wrote the authors, who strongly urged that hemorrhagic complications and death resulting from trauma be included as part of routine surveillance of all newly approved oral anticoagulants. The authors also argued that "the ability to perform rapid dialysis in patients with bleeding whose condition is unstable or in those with large intracranial hemorrhages will present an incredible challenge, even at level 1 trauma centers."
Both Dr. Cipolle and Mr. Gallagher emphasized that institutions should have a protocol in place for anticoagulant reversal. The protocol should be based on evidence and practice guidelines, be transparent and modifiable, and identify specific anticoagulant agents, triggers for reversal such as intracranial hemorrhage or solid organ injury, and reversal strategies and methods for monitoring both the use of anticoagulants and reversal strategies, Mr. Gallagher said.