EXPERT OPINION FROM THE ACS CLINICAL CONGRESS
SAN DIEGO (FRONTLINE MEDICAL NEWS) – A new class of anticoagulants competing with or replacing warfarin and heparin is now commonly seen in patients and can require new strategies for management in the surgical setting. New drugs to reverse anticoagulation agents now need to be routinely considered in advance of surgery.
“They’re all over the place. It feels like everyone I see is on an anticoagulant, especially the new anticoagulants,” said Carlos V.R. Brown, MD, FACS, associate professor of surgery and chief of the division of acute care surgery at the University of Texas at Austin. “There’s a lot more learning that has to take place into how these medications work and how to take care of patients who use them.”
Dr. Brown spoke about management of anticoagulants at the annual clinical congress of the American College of Surgeons and in a follow-up interview. He offered some details during his San Diego presentation about the significant limitations of the traditional blood thinners.
“Warfarin is slow, unpredictable, and requires monitoring and dose adjustment,” he said. In addition, interactions with food and other medications can be problematic, he said. The injectable drug heparin, meanwhile, requires monitoring and frequent dose adjustments, he said. “We’re in search of the ideal anticoagulant – one that’s oral, has a wide therapeutic window, is very predictable with rapid onset, and has minimal interaction with other food or drugs.”
Here’s the hitch, he said: “It probably doesn’t exist.”
There are now several alternatives to the old standbys on the market. One class, the direct thrombin inhibitor, is led by dabigatran etexilate (Pradaxa). Another class, the factor Xa inhibitors, includes rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). From an elective surgery standpoint, Dr. Brown said in an interview, it has become important to understand how to reverse the effects of anticoagulants before a procedure.
To determine levels of the drugs, a TT (thrombin time) screening test is recommended for dabigatran and an anti-Xa test for rivaroxaban, apixaban, and edoxaban said Dr. Brown, referring to a 2017 study published in Critical Care Clinics. The paper summarized the available evidence and provided the optimal reversal strategy for bleeding patients with trauma on novel oral anticoagulants. The report also noted that newer blood thinners have a half-life of 7 or 12 hours and reach peak plasma level at 1-4 hours, depending on the medication ( Crit Care Clin. 2017;33135-52 ).
There may be no time to determine blood thinner levels in emergency situations. In those cases, patient or caregiver history about recent doses can be crucial, Dr. Brown said. “Knowing the patient’s history is going to be a key component,” he said.
Surgeons can turn to a variety of options to reverse the newer anticoagulants in an emergent setting, but only dabigatran has a Food and Drug Administration–approved reversal agent. Activated charcoal, PCC (Kcentra) and aPCC (FEIBA) can reverse dabigatran and oral factor Xa inhibitors, Dr. Brown said. Dialysis is also an option for dabigatran.
Another option to reverse dabigatran may be idarucizumab (Praxbind), a reversal agent. A 2017 industry-funded, open-label study reported successful results. It has been shown to work rapidly, Dr. Brown said, and the drug is now FDA approved ( N Engl J Med. 2017 Aug 3;377:431-41 ).
For oral factor Xa inhibitors, Dr. Brown said, andexanet alfa is now in a trial and doesn’t yet have FDA approval. “Presumably, it will provide a benefit over PCC because it’s directed at that specific medication,” he said.
Dr. Brown cautioned about the risks of reversing anticoagulants. “Any time you’re reversing an anticoagulant, the side effect is going to be clotting,” boosting the likelihood of events such as heart attack or stroke, he said. “You’re always weighing the risk versus the benefit of reversing.”
Dr. Brown has no relevant disclosures.