Reversal agents of direct oral anticoagulants
| . | Idarucizumab17,26-28 . | Andexanet alfa17,25,27,29 . | 4-Factor PCC17,27,30 . |
|---|---|---|---|
| References | 17,30-33 | 17,25,31,34,35 | 17,31,36 |
| Type of structure | Humanized monoclonal antibody fragment | Recombinant modified factor Xa protein | Coagulation factors II, VII, IX, and X |
| Cost per dose | $350037 | $24 200–$48 40038 | $4050–$810030 |
| FDA approved | 2015 | 2018 | Off-label use |
| Approval based on | RE-VERSE AD study | ANNEXA-4 trial | Multiple observational studies |
| Drug reversed | Dabigatran | Apixaban, rivaroxaban, edoxaban∗ | Dabigatran, apixaban, rivaroxaban, edoxaban, warfarin |
| Mechanism of action | Binds dabigatran and its metabolites with an affinity for dabigatran that is ∼350× greater that of thrombin | Binds and sequesters the factor Xa inhibitors | Contain vitamin K dependent coagulation factors that promote hemostasis (factors II, IX, X, and VII) Some 4-factor PCC contain heparin† Some countries only have access to 3-factor PCC (missing Factor VII) |
| Onset | Within minutes | Rapid | Rapid |
| Dose | 5 g IV (given as 2 separate 2.5 g doses ≤15 minutes apart) | IV bolus (400 or 800 mg), then a continuous infusion for up to 120 min (4 or 8 mg/min) based on the last dose of rivaroxaban (≤10 or >10 mg/unknown) or apixaban (≤5 or >5 mg/unknown), and time of the last dose of rivaroxaban or apixaban (<8 h/unknown or ≥8 h) | PCC for FXa inhibitor reversal, IV 25-50 U/kg or fixed dose of 2000; for dabigatran reversal, IV 50 U/kg |
| Adverse effects | Thromboembolism | Thromboembolism, cardiac arrest, stroke | Thrombosis, stroke, hypotension |
| Thromboembolic events after 30 days | 3.8%-5% | 10%-14% | 4%-8% |
| . | Idarucizumab17,26-28 . | Andexanet alfa17,25,27,29 . | 4-Factor PCC17,27,30 . |
|---|---|---|---|
| References | 17,30-33 | 17,25,31,34,35 | 17,31,36 |
| Type of structure | Humanized monoclonal antibody fragment | Recombinant modified factor Xa protein | Coagulation factors II, VII, IX, and X |
| Cost per dose | $350037 | $24 200–$48 40038 | $4050–$810030 |
| FDA approved | 2015 | 2018 | Off-label use |
| Approval based on | RE-VERSE AD study | ANNEXA-4 trial | Multiple observational studies |
| Drug reversed | Dabigatran | Apixaban, rivaroxaban, edoxaban∗ | Dabigatran, apixaban, rivaroxaban, edoxaban, warfarin |
| Mechanism of action | Binds dabigatran and its metabolites with an affinity for dabigatran that is ∼350× greater that of thrombin | Binds and sequesters the factor Xa inhibitors | Contain vitamin K dependent coagulation factors that promote hemostasis (factors II, IX, X, and VII) Some 4-factor PCC contain heparin† Some countries only have access to 3-factor PCC (missing Factor VII) |
| Onset | Within minutes | Rapid | Rapid |
| Dose | 5 g IV (given as 2 separate 2.5 g doses ≤15 minutes apart) | IV bolus (400 or 800 mg), then a continuous infusion for up to 120 min (4 or 8 mg/min) based on the last dose of rivaroxaban (≤10 or >10 mg/unknown) or apixaban (≤5 or >5 mg/unknown), and time of the last dose of rivaroxaban or apixaban (<8 h/unknown or ≥8 h) | PCC for FXa inhibitor reversal, IV 25-50 U/kg or fixed dose of 2000; for dabigatran reversal, IV 50 U/kg |
| Adverse effects | Thromboembolism | Thromboembolism, cardiac arrest, stroke | Thrombosis, stroke, hypotension |
| Thromboembolic events after 30 days | 3.8%-5% | 10%-14% | 4%-8% |
DOAC, direct oral anticoagulant; PCC, prothrombin complex concentrates.
Activated charcoal can be used for reversal for known ingestion of DOAC within 2 to 4 hours.
Not FDA approved for edoxaban, off-label use recommended by 2020 American College of Cardiology Expert Consensus.
Some PCC contains heparin, so avoid use of heparin-containing PCC in patients with a history of heparin induced thrombocytopenia.