Minor Trauma Led to Death in Pradaxa Patient

A friend of mine was on Pradaxa for a while and she was extremely concerned about bleeding and the lack of a reversal agent.
http://www.medpagetoday.com/Neurology/HeadTrauma/31524?utm_source=cardiodaily&utm_medium=email&utm_content=aha&utm_campaign=03-07-12&eun=gd3r&userid=424561&email=oc1dean@yahoo.com&mu_id=
A dabigatran (Pradaxa) patient's death from a brain hemorrhage following a fall has again highlighted concerns over lack of an effective reversal agent for the drug.
Despite treatment with recombinant factor VII, the 83-year-old man deteriorated rapidly as the bleeding spread across most of the left hemisphere of his brain in just six hours, according to Richard H. Schmidt, MD, PhD, of the University of Utah in Salt Lake City, and colleagues.
"Imbalance and falls are common in this population, and intracranial hemorrhage resulting even from minor trauma may occur with increasing frequency as use of this drug becomes more widespread," they warned in a case report published online in the Journal of Neurosurgery.
A high index of suspicion for catastrophic hemorrhage in dabigatran users is critical so that what limited management options there are can be started without delay, the group urged.
The direct thrombin inhibitor acts at the very end of the coagulation cascade, so factor VIIa and fresh-frozen plasma don't work. Prothrombin complex concentrate hasn't been tested outside of animal models yet.
Dialysis can remove 35% to 60% of circulating dabigatran in two to three hours, but wasn't considered until too late to be effective for the reported case.
The group recommended checking the thrombin time and starting dialysis early along with judicious IV fluids to maintain renal perfusion, which is the main route of dabigatran excretion.
"Caution is necessary, however, because patients with atrial fibrillation have tenuous intravascular volume status, and fluid overload can lead to worsening heart function," they warned in the paper.
Hematologists expressed similar concerns over lack of reversibility in a recent review of a cluster of bleeding episodes in New Zealand, largely involving older patients and those with impaired renal function.
The drug was widely hailed initially for its ability to be given at a fixed dose without the need for frequent adjustments and monitoring.
In the pivotal RE-LY trial, bleeding risks were similar to those with warfarin. But since FDA approval in 2010 for stroke prevention in atrial fibrillation, reports have surfaced of a possible excess of bleeding deaths with the drug, prompting an ongoing safety review by the FDA.
Drugmaker Boehringer Ingelheim has called these reports within what would be expected based on the clinical trial, noting that dabigatran's prescribing information cites a trend for higher major bleed rates with the 150-mg dose versus warfarin in the 75-and-older population.
In the case report, the 83-year-old man had been on 150-mg twice-daily dabigatran for new-onset atrial fibrillation for one month before the ground-level fall at home that sent him to the emergency department.
On arrival, the man was alert and responsive with a normal neurological exam and a Glasgow Coma Scale score of 15. The initial CT scan showed only small, superficial areas of hemorrhage in his right temporal lobe and left temporal and parietal lobes.
Within two hours, he developed slurred speech and his neurological state began to deteriorate rapidly. Repeat CT imaging showed significant progression of right parenchymal and left frontal hemorrhages.
The neurosurgical team members knew they had limited options to reverse the blood thinner, which had left the patient with an international normalized ratio of 1.4 and a thrombin time over 150 seconds compared with the normal 15 to 20 seconds.
Despite trying a weight-based dose of recombinant factor VII for its rapid onset of action, mental status continued to slide to the point where the man lapsed into a coma (Glasgow Coma Scale score 6) and required emergency endotracheal intubation.
His final CT scan six hours after admission showed hemorrhage encompassing most of the left hemisphere and effacing the left lateral ventricle.
The patient was transitioned to palliative care after extensive discussion with his family and died shortly thereafter.
Dabigatran is only the first in a class of direct thrombin inhibitors that may raise these problems, Schmidt's group noted.
Others are on the horizon, "and these agents will likely have similar risks for catastrophic progression of traumatic injuries," they warned.