A 67-year-old woman with a recent history of deep vein thrombosis treated with apixaban 5 mg BID was admitted to the ICU for postoperative respiratory insufficiency following elective ventral hernia repair. She was extubated successfully on postoperative day 2. Her anticoagulation was bridged appropriately and home apixaban restarted on day 3 in anticipation of discharge. She suddenly became altered, hemodynamically unstable, and her bed was filled with melena. Vital signs were noted as follows:
What is the most effective form of anticoagulation reversal for this patient?
A. Fresh Frozen PlasmaCorrect Answer: B
When life-threatening hemorrhage or bleed in a critical area occurs in the setting of anticoagulation, rapid reversal is crucial. The efficacy of FFP for the reversal of Xa inhibitors is modest at best. FFP has an INR of ∼1.4, must be blood group specific, needs to be thawed before administration, and a volume of 10 to 15 mL/kg is needed. The delay in administration, potential for volume overload, transfusion related acute lung injury, and more effective options make this a less than ideal treatment.
PCC may be useful in anticoagulation reversal but not the best option. PCC comes in two types, 4 factor and 3 factor. The 4 factor PCC contains all of the vitamin K–dependent coagulation factors—II, VII, IX, and X. The 3 factor PCC does not contain factor VII and would not be good for vitamin K antagonists. Current consensus guidelines suggest 50 µg/kg of 4 factor PCC should be given to those on a factor Xa inhibitor with life-threatening bleeding or bleeding in a critical area.
Adnexanet Alfa is a decoy factor Xa with no active site. It has shown promise in phase III clinical trials. The ANNEXA-4 (Adnexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors) clinical trial is currently underway and shows effective reversal. If available, this is the best option. Recent FDA fast-track approval will likely bring this to the frontline for reversal of factor Xa inhibitors.
Because of its short half-life and the NOACs differing pharmacology, dosage varies by drug. Adnexanet alfa bolus is no longer effective 2 hours after it is administered and requires an infusion. Patients on apixaban 5 mg BID require a 400 mg bolus followed by a continuous infusion of 4 mg/min for 2 hours. Those on rivaroxaban 20 mg daily require an 800 mg bolus followed by a continuous infusion of 8 mg/min for 2 hours.
Idarucizumab is a monoclonal antibody specific to dabigatran. Axiomatically, it is not an appropriate reversal agent for apixaban.
References:
Barnes GD. Consensus for management of bleeding on oral anticoagulants. J Am Coll Cardiol. 2017;(2):4-6. Available at https://www.acc.org/latest-in-cardiology/ten-points-toremember/2017/11/29/17/23/2017-acc-expert-consensus-of-bleeding-onoacs.
Raval AN, Cigarroa JE, Chung MK, et al. Management of patients on non–vitamin k antagonist oral anticoagulants in the acute care and periprocedural setting: a scientific statement from the American Heart Association. Circulation. 2017;135(10). Available at https://www.ahajournals.org/doi/10.1161/CIR.0000000000000477.
Kaatz S, Bhansali H, Gibbs J, Lavender R, Mahan CE, Paje DG. Reversing factor Xa inhibitors – clinical utility of andexanet alfa. J Blood Med. 2017;8:141-149. Available at http://www.ncbi.nlm.nih.gov/pubmed/28979172.