Anticoagulant reversal for life-threatening bleeds

Factor Xa Inhibitors

Anticoagulant	Half-life	Removed by HD	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
Edoxaban (Savaysa®)	10-14 hrs (longer in renal impairment)	~ 25%	As above
Rivaroxaban (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

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 50 mg 8-12 hours since last dose: Protamine 25 mg >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
Heparin	30-90 min (dose dependent)	Partial	Turn off infusion Protamine 50 mg IV

Warfarin (Coumadin®)

INR	Clinical scenario	Management
Any INR	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 2.5 mg oral or 1-2 mg IV infusion over 30 minutes (IV administration of vitamin K has faster onset of action)
	Rapid reversal required	*Hold warfarin *Consider vitamin K 2.5 mg oral or 1-2 mg 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 2.5 mg oral or 1 mg 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 2.5 mg oral

See Also

• Coagulopathy (main)

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.