Difference between revisions of "Anticoagulant reversal for life-threatening bleeds"

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===Factor Xa Inhibitors===
+
{{Factor Xa Inhibitor Reversal}}
 +
 
 +
===Direct Thrombin Inhibitor===
 
{| {{table}}
 
{| {{table}}
 
| align="center" style="background:#f0f0f0;"|'''Anticoagulants'''
 
| align="center" style="background:#f0f0f0;"|'''Anticoagulants'''
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| align="center" style="background:#f0f0f0;"|'''Strategies to reverse or minimize anticoagulant effects'''
 
| align="center" style="background:#f0f0f0;"|'''Strategies to reverse or minimize anticoagulant effects'''
 
|-
 
|-
| Apixaban (Eliquis®)||8-15 hrs (longer in renal impairment)||No||*If ingested within 2 hours, administer activated charcoal *4-factor PCC (Kcentra™)^ **25units/kg—max 2500 units for treatment of documented intracranial hemorrhage **50 units/kg—max 5000 units for all other life-threatening bleeds
+
| [[Argatroban]]||40-50 min ||~ 20%||Turn off infusion
|-
 
| Edoxaban (Savaysa®)||10-14 hrs (longer in renal impairment)||~ 25%||As above
 
 
|-
 
|-
| Rivaroxaban (Xarelto®)||9-13 hrs (longer in renal impairment)||No||As above
+
| [[Bivalirudin]] (Angiomax®)||25 min (up to 1 hr in severe renal impairment)||~ 25%||As above
 
|-
 
|-
| Fondaparinux (Arixtra®)||17-21 hrs (significantly longer in renal impairment)||No||4-factor PCC (Kcentra™)* 50 units/kg—max 5000 units
+
| [[Dabigatran]] (Pradaxa®)||14-17 hrs (up to 34 hrs in severe renal impairment)||~ 65%||
 +
*If ingested within 2 hours, administer [[activated charcoal]]
 +
*[[Idarucizumab]] (Praxbind®) 5g IV
 +
*For end stage renal disease patient with pre-existing vascular access, consult nephrology to consider dialysis.
 
|}
 
|}
  
===Direct Thrombin Inhibitor===
+
===Heparins===
 
{| {{table}}
 
{| {{table}}
 
| align="center" style="background:#f0f0f0;"|'''Anticoagulants'''
 
| align="center" style="background:#f0f0f0;"|'''Anticoagulants'''
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| align="center" style="background:#f0f0f0;"|'''Strategies to reverse or minimize anticoagulant effects'''
 
| align="center" style="background:#f0f0f0;"|'''Strategies to reverse or minimize anticoagulant effects'''
 
|-
 
|-
| Argatroban||40-50 min ||~ 20%||Turn off infusion
+
| [[Dalteparin]] (Fragmin®)||3-5 hrs (longer in renal impairment)||~ 20%||
 +
*Use protamine for partial neutralization (~60%)
 +
*[[Protamine]] IV:
 +
**< 8 hours since last dose: [[Protamine]] 50mg
 +
**8-12 hours since last dose: [[Protamine]] 25mg
 +
**>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
 +
*Obtain baseline anti-Xa activity level
 +
*Monitor anti-Xa activity level to confirm reversal
 
|-
 
|-
| Bivalirudin (Angiomax®)||25 min (up to 1 hr in severe renal impairment)||~ 25%||As above
+
| [[Enoxaparin]] (Lovenox®)||3-5 hrs (longer in renal impairment)||~ 20%||As above
 
|-
 
|-
| Dabigatran (Pradaxa®)||14-17 hrs (up to 34 hrs in severe renal impairment)||~ 65%||If ingested within 2 hours, administer activated charcoal *Idarucizumab (Praxbind®) 5g IV *For end stage renal disease patient with pre-existing vascular access, consult nephrology to consider dialysis.
+
| [[Unfractionated heparin]]||30-90 min (dose dependent)||Partial||
 +
*Turn off infusion
 +
*[[Protamine]] 50mg IV
 
|}
 
|}
  
===Heparins===
+
===[[Warfarin]](Coumadin®)===
 
{| {{table}}
 
{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Anticoagulants'''
+
| align="center" style="background:#f0f0f0;"|'''INR'''
| align="center" style="background:#f0f0f0;"|'''Half-life'''
+
| align="center" style="background:#f0f0f0;"|'''Clinical scenario'''
| align="center" style="background:#f0f0f0;"|'''Removed by HD'''
+
| align="center" style="background:#f0f0f0;"|'''Management'''
| align="center" style="background:#f0f0f0;"|'''Strategies to reverse or minimize anticoagulant effects'''
+
|-
 +
| 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
 
|-
 
|-
| Dalteparin (Fragmin®)||3-5 hrs (longer in renal impairment)||~ 20%||*Use protamine for partial neutralization (~60%) *Protamine IV: **< 8 hours since last LMWH dose: Protamine 50 mg **8-12 hours since last LMWH dose: Protamine 25 mg **>12 hours since last LMWH 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 *Obtain baseline anti-Xa activity level *Monitor anti-Xa activity level to confirm reversal
+
| ||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)
 
|-
 
|-
| Enoxaparin (Lovenox®)||||||As above
+
| < 4.5||No bleeding||
 +
*Hold warfarin until INR in therapeutic range
 
|-
 
|-
| Heparin||30-90 min (dose dependent)||Partial||*Turn off infusion *Protamine 50 mg IV
+
| ||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==
 
<references/>
 
<references/>
 +
*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.
 +
*Xarelto prescribing information. Titusville, NJ: Janssen Pharmaceuticals, Inc.; December 2014.
 +
*Pradaxa prescribing information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; January 2012.
 +
*Eliquis prescribing information. Princeton, NJ: Bristol Myers Squibb; December 2012.
 +
*Savaysa prescribing information. Parsippany, NJ: Daiichi Sankyo, Inc.; November 2015.
 +
 +
[[Category:Heme/Onc]]

Revision as of 11:27, 9 December 2019

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
  • If ingested within 2 hours, administer activated charcoal
  • 4-factor PCC (Kcentra™)^
    • 25units/kg—max 2500 units for treatment of documented intracranial hemorrhage
    • 50 units/kg—max 5000 units for all other life-threatening bleeds
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 (Pradaxa®) 14-17 hrs (up to 34 hrs in severe renal impairment) ~ 65%
  • If ingested within 2 hours, administer activated charcoal
  • Idarucizumab (Praxbind®) 5g IV
  • For end stage renal disease patient with pre-existing vascular access, consult nephrology to consider dialysis.

Heparins

Anticoagulants Half-life Removed by HD Strategies to reverse or minimize anticoagulant effects
Dalteparin (Fragmin®) 3-5 hrs (longer in renal impairment) ~ 20%
  • Use protamine for partial neutralization (~60%)
  • Protamine IV:
    • < 8 hours since last dose: Protamine 50mg
    • 8-12 hours since last dose: Protamine 25mg
    • >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
  • Obtain baseline anti-Xa activity level
  • Monitor anti-Xa activity level to confirm reversal
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
  • 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

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[5]

References

  1. Eliquis prescribing information. Princeton, NJ: Bristol Myers Squibb; December 2012.
  2. Savaysa prescribing information. Parsippany, NJ: Daiichi Sankyo, Inc.; November 2015.
  3. Xarelto prescribing information. Titusville, NJ: Janssen Pharmaceuticals, Inc.; December 2014.
  4. 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
  5. 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.
  • Xarelto prescribing information. Titusville, NJ: Janssen Pharmaceuticals, Inc.; December 2014.
  • Pradaxa prescribing information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; January 2012.
  • Eliquis prescribing information. Princeton, NJ: Bristol Myers Squibb; December 2012.
  • Savaysa prescribing information. Parsippany, NJ: Daiichi Sankyo, Inc.; November 2015.