LAKE BUENA VISTA, FLA. – Patients on one of the powerful new oral anticoagulants are left without a good antidote for bleeding if they experience a traumatic injury.
The use of these agents is climbing as baby boomers age and the number of patients with atrial fibrillation continues its steady rise from 2.0 million in 1995 to a projected 4.34 million by 2030.
Dr. Mark Cipolle
"If you think it’s an epidemic now, it will become even more so in the coming years," Dr. Mark Cipolle, medical director of trauma and neurocritical care at Christiana Care Health System in Wilmington, Del., said at the annual meeting of the Eastern Association for the Surgery of Trauma.
Currently, no specific antidote is available for dabigatran (Pradaxa) or the factor Xa inhibitor rivaroxaban (Xarelto), both of which are approved for stroke prevention in nonvalvular atrial fibrillation and for deep vein thrombosis following hip or knee replacement surgery.
The oral Xa inhibitor apixaban (Eliquis) is under priority review for stroke and DVT prevention in atrial fibrillation and will likely move, sans antidote, into the marketplace later this year based on robust results from the recent ARISTOTLE trial.
Vitamin K and protamine sulfate are not expected to affect the anticoagulant activity of the new oral anticoagulants. Some centers have had anectodal success in reversing dabigatran with activated prothrombin complex concentrates (aPCCs), but this has not been widely adopted, according to Dr. Cipolle.
"Some of my colleagues in pharmacy think this may be the drug to help us reverse dabigatran ... but our blood bank hematologists aren’t thrilled about going to this because of the development of antibodies for the new agents," he said.
The two aPCCs available in the United States are factor eight inhibitor binding activity (FEIBA) and anti-inhibitor coagulant complex, heat treated (Autoplex T); both are indicated for bypass therapy in patients with acquired inhibitors and contain the coagulation factors II, VII, IX, and X.
Dr. John Gallagher
One of the first randomized trials to look at a specific PCC (Cofact) showed that a single bolus immediately and completely reversed the anticoagulation effect of rivaroxaban in 12 healthy volunteers who were taking 20 mg twice daily, but the PCC had no influence on the effect of dabigatran 150 mg twice daily (Circulation 2011;124:1573-9), said copanelist John Gallagher, clinical nurse specialist for the surgical/trauma ICU at the Hospital of the University of Pennsylvania in Philadelphia.
Recombinant activated factor VIIa has been widely studied in trauma, but not for this specific indication. Early research on antibody monoclonal development is showing promise, Dr. Cipolle said. A recent study described a monoclonal mouse antibody with a high and specific affinity to inhibit dabigatran in both human plasma and whole blood and in a rat in vivo model (J. Am. Coll. Cardiol. 2011;57:E1130).