Reversal

Agents Indication Mechanism Dosing Monitoring Pearls JHHS RESTRICTIONS

Individualize dosing based on current pre-dose INR. Dosage is
expressed in units of factor IX activity. Administer with vitamin K
For ICH, 10 mg IV phytonadione For patients with intracranial
concurrently. Repeat dosing is not recommended.
(vitamin K) must be ordered and hemorrhage in association with an
4 Factor unactivated PCC administered to ALL PATIENTS INR > 1.4 in the setting of warfarin
Pretreatment INR 2 to <4: Administer 25 units/kg; maximum dose:
INR (baseline and at 30 receiving the Kcentra®. This can therapy
2,500 units
First line Vitamin K Prothrombin complex minutes post dose) also be considered for patients with
antagonist (VKA) concentrate provides an cardiac wall perforation, but is not For patients with cardiac wall
Pretreatment INR 4 to 6: Administer 35 units/kg; maximum dose:
reversal in patients with increase in the levels of the Clinical response during required. The administration of perforation and/or cardiac
3,500 units
KCENTRA® acute major bleeding or vitamin K-dependent and after treatment phytonadione must not delay the tamponade in association with an
need for an urgent coagulation factors (II, VII, administration of Kcentra®.*** INR > 1.4 in the setting of warfarin
Pretreatment INR >6: Administer 50 units/kg; maximum dose: 5,000
surgery/invasive IX, and X) with the addition Signs of therapy
units
procedure of protein C and protein S thromboembolism and Reconstituted preparations should
hypersensitivity reactions be used within 4 hours Life threatening hemorrhage in a
**Patients can be given a conservative dose of 1500 units x 1 dose
patient on warfarin resulting in
with a repeat INR taken 30-60 minutes post dose administration. It is
Onset of action: Rapid; significant initiation of the massive
recommended to give KCentra® 1500 units x 1 dose, wait 30-60
INR decline within 10 minutes transfusion protocol
minutes post dose and then recheck the INR. If the INR ≥ 2, a
supplemental dose based upon the INR reading should be given.

Signs/symptoms of
disseminated intravascular
coagulation (DIC), acute
coronary ischemia, and
FEIBA can only be ordered by ED,
thromboembolic events, Reconstituted preparations should
Second line reversal 50 unit/kg/dose (max dose is 100 units/kg; TDD is 200 units/kg) ICU for NOAC (Non-Vitamin K Oral
especially if >100 units/kg be used within 3 hours
FEIBA® agent for several 4 Factor Activated PCC Anticoagulant) reversal, or
is administered;
anticoagulants Maximum infusion rate is 2 units/kg/min Hematology for hematologic
hemoglobin and Onset of action: ~15-30 minutes
indications
hematocrit

Signs/symptoms of
hypersensitivity reactions

Monitor for re-elevation

of coagulation parameters
(i.e. aPTT)

In patients overdosed with

dabigatran, consider:
Baseline aPTT, repeat at 2
hours postexposure (if
known) or post- Restricted to use for reversal of
Onset of action: Effects observed
Idarucizumab Humanized Monoclonal 2.5 g IV x 2 doses within 15 minutes of each other (doses should be presentation (if exposure dabigatran for emergency
Dabigatran reversal within minutes and hemostasis is
[PRAXBIND®] Antibody administered within an hour of removal from vials) time is unknown) and surgery/procedure or in life-
restored at a median of 11.4 hours
every 12 hours thereafter threatening bleeding
until aPTT returns to
normal

Signs/symptoms of
clinically relevant
bleeding,
thromboembolic events,
and hypersensitivity
 Low dose: 400 mg IV bolus administered at a rate of ~30 mg/minute,
followed 2 minutes later by 4 mg/minute IV infusion for up to 120
Andexanet alfa binds and minutes Restricted to approval by
sequesters the FXa - use for any ingestion ≥8 hours Intensivists/ER Physicians for use
Signs/symptoms of
inhibitors rivaroxaban and - use for apixaban ≤ 5mg in patients with intrcranial
First line reversal of arterial and venous Reconstituted ANDEXXA in IV bags
apixaban. In addition, - use for rivaroxaban ≤ 10mg hemorrhage meeting all of the
anticoagulation from thromboembolic events, is stable at room temperature for
Andexanet Alfa andexanet alfa inhibits the - use for edoxaban ≤ 30mg following criteria:
apixaban, rivaroxaban, ischemic events, or up to 8 hours
[Andexxa®] activity of Tissue Factor -last dose of apixaban,
or edoxaban with life- cardiac arrest, hemostasis,
Pathway Inhibitor (TFPI), High dose: 800 mg IV bolus administered at a rate of ~30 mg/minute, rivaroxaban, or edoxaban within
threatening bleeding and hypersensitivity Onset of Action: Rapid
increasing tissue factor- followed 2 minutes later by 8 mg/minute IV infusion for up to 120 18 hours
reactions
initiated thrombin minutes -Glasgow Coma Scale Score ≥ 5
generation - use for apixaban > 5mg/unknown -No administration of Kcentra,
- use for rivaroxaban > 10mg/unknown FEIBA or NovoSeven within 48
- use for edoxaban > 30mg/unknown hours

Heparin reversal (<2.5 hrs):1 mg of protamine to 100 units of heparin

Enoxaparin reversal (<8 hrs): 1 mg of protamine to 1 mg of enoxaparin

First line Combines with heparin to Signs/symptoms of Onset of action: IV: Heparin
PROTAMINE
Heparin/LMWH reversal form a neutralized salt Enoxaparin reversal (>8 hrs): 0.5 mg of protamine to 1 mg of hypersensitivity reactions neutralization: ~5 minutes
enoxaparin

Max dose is 50 mg over 10 mins

INR will decrease over ~24-

INR supratherapeutic but < 4.5: Hold warfarin dose, no vitamin K
48 hours (oral) and ~12-14
hours (IV); more frequent Subcutaneous and IM routes are
INR 4.5-10: Hold warfarin dose; no vitamin K
Vitamin K / INR monitoring and not recommended
Replaces coagulation factors
Phytonadione Warfarin reversal additional vitamin K doses
II, VII, IX, and X INR ≥ 10: Hold warfarin, administer vitamin K 2.5-5 mg PO
[MEPHYTON®] may be necessary. Onset of action: 6-10 hours (oral);
1-2 hours (IV)
Major bleeding despite INR: Administer vitamin K 5-10 mg IV with
Signs/symptoms of
Kcentra
hypersensitivity reactions
APIXABAN:
Conversion from warfarin to apixaban: Discontinue warfarin and initiate apixaban when INR is <2
Conversion from apixaban to warfarin: Note: Apixaban affects the INR; measuring the INR during warfarin therapy may not be useful for determining an appropriate dose of
warfarin. If continuous anticoagulation is necessary, discontinue apixaban and begin both a parenteral anticoagulant with warfarin when the next dose of apixaban is
due; discontinue parenteral anticoagulant when INR reaches an acceptable range
Conversion between apixaban and other non-warfarin anticoagulants: Discontinue anticoagulant being taken and begin the other at the next scheduled dose

DABIGATRAN:
Conversion from a parenteral anticoagulant: Initiate dabigatran ≤2 hours prior to the time of the next scheduled dose of the parenteral anticoagulant (eg, enoxaparin) or at the
time of discontinuation for a continuously administered parenteral drug (eg, IV heparin); discontinue parenteral anticoagulant at the time of dabigatran initiation.
Conversion to a parenteral anticoagulant: Wait 12 hours (CrCl ≥30 mL/minute) or 24 hours (CrCl <30 mL/minute) after the last dose of
dabigatran before initiating a parenteral anticoagulant.
Conversion from warfarin: Discontinue warfarin and initiate dabigatran when INR <2.0
Conversion to warfarin: Since dabigatran contributes to INR elevation, warfarin’s effect on the INR will be better reflected only after
dabigatran has been stopped for ≥2 days. Start time must be adjusted based on CrCl:
CrCl >50 mL/minute: Initiate warfarin 3 days before discontinuation of dabigatran
CrCl 31 to 50 mL/minute: Initiate warfarin 2 days before discontinuation of dabigatran
CrCl 15 to 30 mL/minute: Initiate warfarin 1 day before discontinuation of dabigatran (dabigatran use is contraindicated in
Canadian labeling when CrCl <30 mL/minute).
CrCl <15 mL/minute: There are no recommendations provided in the U.S. manufacturer’s labeling.

RIVAROXABAN:
Conversion from warfarin: Discontinue warfarin and initiate rivaroxaban as soon as INR falls to <3.0 (U.S. labeling) or ≤2.5 (Canadian labeling)
Conversion to warfarin: Note: Rivaroxaban affects INR; therefore, initial INR measurements after initiating warfarin may be unreliable.
Discontinue rivaroxaban and initiate both warfarin and a parenteral anticoagulant at the time the next dose of rivaroxaban would have been taken
Conversion from continuous infusion unfractionated heparin: Initiate rivaroxaban at the time of heparin discontinuation
Conversion to continuous infusion unfractionated heparin: Discontinue rivaroxaban and initiate continuous infusion heparin at the time the next dose of rivaroxaban would have
been taken.
Conversion from anticoagulants (other than warfarin and continuous infusion unfractionated heparin):
Discontinue current anticoagulant and initiate rivaroxaban ≤2 hours prior to the next regularly scheduled evening dose of the discontinued anticoagulant.

Conversion to other anticoagulants (other than warfarin): Discontinue rivaroxaban and initiate the anticoagulant at the time the next dose of rivaroxaban would have been taken