Anticoagulant reversal for life-threatening bleeds: Difference between revisions
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{{Factor Xa Inhibitor Reversal}} | |||
===Direct Thrombin Inhibitor=== | ===Direct Thrombin Inhibitor=== | ||
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| [[Bivalirudin]] (Angiomax®)||25 min (up to 1 hr in severe renal impairment)||~ 25%||As above | | [[Bivalirudin]] (Angiomax®)||25 min (up to 1 hr in severe renal impairment)||~ 25%||As above | ||
|- | |- | ||
| [[Dabigatran]] (Pradaxa®)||14-17 hrs (up to 34 hrs in severe renal impairment)||~ 65%|| | | [[Dabigatran]]<ref>*Pradaxa prescribing information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; January 2012.</ref> (Pradaxa®)||14-17 hrs (up to 34 hrs in severe renal impairment)||~ 65%|| | ||
*If ingested within 2 hours, administer [[activated charcoal]] | *If ingested within 2 hours, administer [[activated charcoal]] | ||
*[[Idarucizumab]] (Praxbind®) 5g IV | *[[Idarucizumab]] (Praxbind®) 5g IV | ||
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*Use protamine for partial neutralization (~60%) | *Use protamine for partial neutralization (~60%) | ||
*[[Protamine]] IV: | *[[Protamine]] IV: | ||
**< 8 hours since last dose: [[Protamine]] | **< 8 hours since last dose: [[Protamine]] 50mg | ||
**8-12 hours since last dose: [[Protamine]] | **8-12 hours since last dose: [[Protamine]] 25mg | ||
**>12 hours since last dose: Unlikely useful unless CrCl < 30 mL/min (or 25mg fixed dose) | **>12 hours since last dose: Unlikely useful unless CrCl < 30 mL/min (or 25mg fixed dose) | ||
*Dose of protamine for each 100 units dalteparin or 1mg of enoxaparin administered | *Dose of protamine for each 100 units dalteparin or 1mg of enoxaparin administered | ||
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| [[Enoxaparin]] (Lovenox®)||3-5 hrs (longer in renal impairment)||~ 20%||As above | | [[Enoxaparin]] (Lovenox®)||3-5 hrs (longer in renal impairment)||~ 20%||As above | ||
|- | |- | ||
| [[ | | [[Unfractionated heparin]]||30-90 min (dose dependent)||Partial|| | ||
*Turn off infusion | *Turn off infusion | ||
*[[Protamine]] | *[[Protamine]] 50mg IV | ||
|} | |} | ||
===Warfarin (Coumadin®)=== | ===[[Warfarin]] (Coumadin®)=== | ||
{| {{table}} | |||
| align="center" style="background:#f0f0f0;"|'''INR''' | |||
| align="center" style="background:#f0f0f0;"|'''Clinical scenario''' | |||
| align="center" style="background:#f0f0f0;"|'''Management''' | |||
|- | |||
| Any||Serious or life-threatening bleed|| | |||
*Hold [[warfarin]] | |||
*Give [[vitamin K]] 10mg IV infusion over 30 minutes | |||
*Give [[FFP]]/plasma or | |||
*Consider 4-factor [[PCC]] (Kcentra™)—preferred for life-threatening bleeds | |||
|- | |||
| > 10||No bleeding|| | |||
*Hold warfarin until INR in therapeutic range | |||
*Consider [[vitamin K]] 2.5mg oral or 1-2mg IV infusion over 30 minutes (IV administration of vitamin K has faster onset of action) | |||
|- | |||
| ||Rapid reversal required|| | |||
*Hold warfarin | |||
*Consider [[vitamin K]] 2.5mg oral or 1-2mg IV infusion over 30 minutes (IV administration of vitamin K has faster onset of action) | |||
|- | |||
| 4.5-10||No bleeding|| | |||
*Hold warfarin until INR in therapeutic range | |||
*Consider [[vitamin K]] 2.5mg oral | |||
|- | |||
| ||Rapid reversal required|| | |||
*Hold warfarin | |||
*Consider [[vitamin K]] 2.5mg oral or 1mg IV infusion (IV administration of vitamin K has faster onset of action) | |||
|- | |||
| < 4.5||No bleeding|| | |||
*Hold warfarin until INR in therapeutic range | |||
|- | |||
| ||Rapid reversal required|| | |||
*Hold warfarin | |||
*Consider [[vitamin K]] 2.5mg oral | |||
|} | |||
==See Also== | ==See Also== | ||
*[[Coagulopathy (main)]] | *[[Coagulopathy (main)]] | ||
*[[Anti-platelet agent reversal]] | |||
==External Links== | ==External Links== | ||
*[https://journalfeed.org/article-a-day/2019/anticoagulant-reversal-strategies-and-coi 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<ref>[https://www.ncbi.nlm.nih.gov/pubmed/31732375?dopt=AbstractPlus 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]</ref> | |||
==References== | ==References== | ||
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*Harbor-UCLA Medical Center Guidelines Approved by Anticoagulation Subcommittee on 3/17/2016 Approved by Pharmacy and Therapeutic Committee on 3/17/2016 | *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. | *Hatfield L and Chen SL. University of North Carolina Healthcare Anticoagulation Reversal Guidelines. June 2014. | ||
[[Category:Heme/Onc]] | |||
Latest revision as of 23:15, 6 January 2020
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.