Anticoagulant reversal for life-threatening bleeds
Factor Xa Inhibitor Reversal
Anticoagulant | Half-life | Removed by HD | Strategies to reverse or minimize anticoagulant effects |
Apixaban[1] (Eliquis®) | 8-15 hrs (longer in renal impairment) | No |
|
Edoxaban[2] (Savaysa®) | 10-14 hrs (longer in renal impairment) | ~ 25% | As above |
Rivaroxaban[3] (Xarelto®) | 9-13 hrs (longer in renal impairment) | No | As above |
Fondaparinux (Arixtra®) | 17-21 hrs (significantly longer in renal impairment) | No | 4-factor PCC (Kcentra™)^ 50 units/kg—max 5000 units |
^Off-label
Andexanet alfa
FDA approved in May 2018, limited availability June 2018
- Cost is $20,000 to $55,000 per dose
- Trial that led to FDA approval does not have the most sound evidence behind it [4]:
- Prospective single center single group study of 352 patients receiving a Factor Xa Inhibitor (apixaban, rivaroxaban, edoxaban, enoxaparin) with life threatening bleed (those with expected survival <1 month were excluded).
- Anti-Factor Xa activity was decreased in all groups. 82% were judged to have excellent hemostatic control. 14% mortality rate at 30 days.
- No comparison group available. It is unlikely that following anti-Factor Xa activity as a lab value is clinically important. High mortality rate even after excluding sick patients.
Low Dose
400 mg IV bolus at rate of ~30 mg/minute, followed 2 minutes later by 4 mg/minute for up to 120 minutes
High Dose
800 mg IV bolus at rate of ~30 mg/minute, followed 2 minutes later by 8 mg/minute for up to 120 minutes
Direct Thrombin Inhibitor
Anticoagulants | Half-life | Removed by HD | Strategies to reverse or minimize anticoagulant effects |
Argatroban | 40-50 min | ~ 20% | Turn off infusion |
Bivalirudin (Angiomax®) | 25 min (up to 1 hr in severe renal impairment) | ~ 25% | As above |
Dabigatran[5] (Pradaxa®) | 14-17 hrs (up to 34 hrs in severe renal impairment) | ~ 65% |
|
Heparins
Anticoagulants | Half-life | Removed by HD | Strategies to reverse or minimize anticoagulant effects |
Dalteparin (Fragmin®) | 3-5 hrs (longer in renal impairment) | ~ 20% |
|
Enoxaparin (Lovenox®) | 3-5 hrs (longer in renal impairment) | ~ 20% | As above |
Unfractionated heparin | 30-90 min (dose dependent) | Partial |
|
Warfarin (Coumadin®)
INR | Clinical scenario | Management |
Any | Serious or life-threatening bleed | |
> 10 | No bleeding |
|
Rapid reversal required |
| |
4.5-10 | No bleeding |
|
Rapid reversal required |
| |
< 4.5 | No bleeding |
|
Rapid reversal required |
|
See Also
External Links
- JournalFeed Summary with Flowsheet of ”Anticoagulant Reversal Strategies in the Emergency Department Setting: Recommendations of a Multidisciplinary Expert Panel.” by Baugh et. al. from Annals 2019[6]
References
- ↑ Eliquis prescribing information. Princeton, NJ: Bristol Myers Squibb; December 2012.
- ↑ Savaysa prescribing information. Parsippany, NJ: Daiichi Sankyo, Inc.; November 2015.
- ↑ Xarelto prescribing information. Titusville, NJ: Janssen Pharmaceuticals, Inc.; December 2014.
- ↑ Connolly SJ, Crowther M, Eikelboom JW, et al. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2019
- ↑ *Pradaxa prescribing information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; January 2012.
- ↑ Baugh et al. Anticoagulant Reversal Strategies in the Emergency Department Setting: Recommendations of a Multidisciplinary Expert Panel. Ann Emerg Med. 2019 Nov 13. pii: S0196-0644(19)31181-3
- Harbor-UCLA Medical Center Guidelines Approved by Anticoagulation Subcommittee on 3/17/2016 Approved by Pharmacy and Therapeutic Committee on 3/17/2016
- Hatfield L and Chen SL. University of North Carolina Healthcare Anticoagulation Reversal Guidelines. June 2014.