TABLE 15.

Reversal Agents for Oral Anticoagulants

	Idarucizumab	Andexanet alfa	4-Factor PCC	Activated PCC
Class	Humanized monoclonal antibody fragment binding to dabigatran and neutralizing anticoagulation effects	A recombinant modified human factor Xa protein binding and sequestering the factor Xa inhibitors	PCC: coagulation factors II, VII, IX, and X Anticoagulation proteins C and S	Nonactivated factors II, IX, and X Activated VII
FDA indications	Reversal of dabigatran effects For emergency surgery/urgent procedures Life-threatening or uncontrolled bleeding	Reversal of apixaban or rivaroxaban For life-threatening or uncontrolled bleeding	The urgent reversal for acute major bleeding or need for an urgent surgery/invasive procedure in patients receiving VKAs	Control and prevention of bleeding episodes, perioperative management, prophylaxis to prevent or reduce bleeding frequency in patients with hemophilia A and B
Off-label indications	N/A	Edoxaban-associated life-threatening bleeding	Reversal of factor Xa inhibitors in patients requiring urgent procedure or with life-threatening bleeding	Dabigatran-associated life-threatening bleeding
Dosing	5-g (2 separate vials of 2.5 g/vial) intravenous infusion over 5 min. Additional 5 g may be given if reappearance of bleeding with elevated coagulation parameters have been observed or patients require second emergency surgery/procedure and elevated coagulation parameters	Low-dose regimen: 400-mg bolus at a target rate of 30 mg/min followed by 4 mg/min for up to 120 min High-dose regimen: 800-mg bolus at a target rate of 30 mg/min followed by 8 mg/min for up to 120 min The recommended dosing is based on apixaban or rivaroxaban, dose, and time since the patient's last dose of apixaban or rivaroxaban	Warfarin reversal based on pretreatment INR (units of factor IX): 1. INR 2-<4: 25 units/kg (up to 2500 units) 2. INR 4-6: 35 units/kg (up to 3500 units) 3. INR >6: 50 units/kg (up to 5000 units) Oral factor Xa inhibitors: 2000 units once or 25 to 50 units/kg	Dabigatran-associated life-threatening bleeding: 50 units/kg once
Onset	Within 5 min	Within 2 min	Within 10 min	Within 30 min
Duration	12-24 h	2 h	8 h	12 h
Monitoring	Coagulation parameters (aPTT, diluted thrombin time, or ecarin clotting time) between 12 and 24 h to assess redistribution of dabigatran from peripheral to plasma	Current commercial anti-Xa activity assays are unsuitable for measuring factor Xa activities after andexanet alfa use	Warfarin reversal: Repeat INR within 30 min after the administration	N/A
Others	Risk of serious reactions (hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, acute liver failure) in patients with hereditary fructose intolerance (due to sorbitol excipient 4 g in each 5 g of idarucizumab) No procoagulant effect based on endogenous thrombin potential	No FDA indication for other factor Xa inhibitors other than apixaban or rivaroxaban Andexanet alfa may interfere with the anticoagulation effect of heparin US black box warning: Serious and life-threatening adverse events (arterial and venous thromboembolism, myocardial infarction, ischemic stroke, cardiac arrest, sudden deaths)	May not be indicated for patients with thromboembolic events in the previous 3 mo It includes heparin Administer intravenous vitamin K 10 mg over 10-20 min in addition to 4-factor PCC	It does not include heparin Coagulation parameters do not correlate with the drug's efficacy Not effective to reverse factor Xa inhibitors

Information in table was obtained from manufacturer package inserts.

aPTT indicates activated partial thromboplastin time; FDA, US Food and Drug Administration; PCC, prothrombin complex concentrate; and VKA, vitamin K antagonists.