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8 The Nurse Practitioner -  Vol. 42, No. 11
NTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS
ERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL
ERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSA
NTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS R
Paras Soni / 123RF
VERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSA
RSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL AGENTS REVERSAL
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The Nurse Practitioner -  November 2017  9
Copyright (c) 2017 Wolters Kluwer Health, Inc. All rights reserved.
1.5
1.5
CONTACT HOURS
CONTACT HOURS
Reversal agents for
oral anticoagulants
Abstract: For more than half a century, warfarin, a vitamin K antagonist, has been
the anticoagulant of choice. However, direct oral anticoagulants are rapidly gaining
in popularity, which poses the need for efficacious reversal agents. This review article
summarizes the strategies and agents used to reverse oral anticoagulants.
By Carrie L. Griffiths, PharmD, BCCCP; Mark L. Vestal; Spencer J. Livengood;
and Samantha Hicks, MSN, ACNP, CCRN
A
nticoagulation therapy is indicated in patients who
have had a venous thromboembolism, atrial fi bril
lation (AF), mechanical valve replacement, and
other coagulation disorders (antiphospholipid antibody
syndrome, Factor V Leiden). Since 2010, when the fi rst direct
oral anticoagulant was approved by the FDA, antithrom
botic therapy has shifted away from the mainstay of therapy,
the vitamin K antagonist, due to recent guideline recom
mendations in antithrombotic therapy.1
In AF, a CHADS2 score or CHA2DS2-VASc score (an
updated version), is used to determine the patient's stroke
risk and need for anticoagulation therapy.2 Several studies
have shown a lower bleeding risk with direct oral antico
agulants (DOACs) over warfarin.3-6 Therefore, clinicians
are considering these agents more often for their patients.
In addition to their improved safety and effi cacy profi le,
DOACs do not require monitoring and have fewer drug
interactions than warfarin.
DOACs do not require monitoring, so it is diffi cult to
determine if the drugs are subtherapeutic, therapeutic, or
supratherapeutic. This has led to a need for effectual antidotes
in the case of an emergency.1 Currently, only one reversal agent
(idarucizumab for dabigatran) has been approved by the FDA,
leaving other DOACs such as rivaroxaban, apixaban, and
edoxaban without reversal agents.
However, warfarin has many reversal options, such as
phytonadione (vitamin K), fresh frozen plasma (FFP), and
prothrombin complex concentrate (PCC). These reversal
agents allow warfarin to be an alternative option for patients
at an increased risk of bleeding, and recent guidelines still
recommend it for certain patients.1 This article reviews key
points regarding available oral anticoagulants (warfarin,
dabigatran, rivaroxaban, apixaban, edoxaban), available
reversal agents (vitamin K, FFP, PCC, idarucizumab), and a
new reversal agent (andexanet alfa), which is currently in
phase III clinical trials.
 Oral anticoagulants
Warfarin
Approved by the FDA in 1954, warfarin is indicated for
prophylaxis and treatment of venous thrombosis, pulmo
nary embolism, thromboembolic complications associated
with AF and/or cardiac valve replacement, and reduction
in the risk of death due to recurrent myocardial infarction
and stroke. It works by inhibiting the synthesis of vitamin
K-dependent clotting factors II, VII, IX, and X and the
anticoagulant proteins C and S, ultimately leading to an
anticoagulant effect.7
Although warfarin is an effective anticoagulant, manag
ing therapy with warfarin is challenging due to the  individual
Keywords: andexanet alfa, apixaban, dabigatran, direct oral anticoagulants, edoxaban, fresh frozen plasma, idarucizumab, phytonadione,
prothrombin complex concentrate, reversal agents, rivaroxaban, vitamin K, warfarin
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Since the first DOAC was approved,
antithrombotic therapy has shifted away from the
mainstay of therapy, the vitamin K antagonist.

Copyright (c) 2017 Wolters Kluwer Health, Inc. All rights reserved.
Reversal agents for oral anticoagulants
variations in dosage requirements that can result in over/
under-anticoagulation. In addition, warfarin has a narrow
therapeutic range, which must be monitored closely to
prevent adverse reactions (such as bleeding). Warfarin's
concentrations can also be affected by vitamin K-containing
foods and other medications, such as amiodarone, fl ucon
azole, and others.8 However, even though warfarin interacts
with many foods and medications, it is still commonly used
for anticoagulation.9
Dabigatran
A direct thrombin inhibitor, dabigatran was approved by
the FDA in 2010 for nonvalvular AF and was the first
DOAC used as an alternative to the vitamin K antagonist.10
This oral prodrug converted by serum esterase works by
binding to both fibrin-bound and unbound thrombin,
which ultimately negates the conversion of fibrinogen
(factor I) to fibrin (factor Ia), preventing the formation of
a thrombus.3,10
Currently, dabigatran is indicated for stroke and sys
temic embolism prophylaxis in nonvalvular AF, treatment
of deep vein thrombosis (DVT) and pulmonary embolism
(PE) in patients who were previously treated with a paren
teral anticoagulant for 5 to 10 days, risk reduction to prevent
recurrence of DVT and PE in patients who were previously
treated, and prophylaxis of DVT and PE in patients under
going hip replacement surgery, which was approved by the
FDA in 2014.11
Rivaroxaban
A factor Xa inhibitor, rivaroxaban was approved by the
FDA in 2011 for nonvalvular AF and venous thromboem
bolism and was the first factor Xa inhibitor to be ap
proved.10 It exerts its pharmacologic effect by binding
directly to free and clot-bound factor Xa, without requir
ing cofactors (antithrombin), thus preventing thrombus
formation and platelet activation. Currently, rivaroxaban
is indicated for risk reduction of stroke and systemic em
bolism in nonvalvular AF, treatment of DVT and PE, risk
reduction to prevent recurrence of DVT and PE in patients
who were initially treated for DVT or PE, and prophy
laxis of DVT and PE in patients undergoing knee or hip
replacement surgery.12
Apixaban
Approved by the FDA in 2012 for the treatment of nonval
vular AF needing anticoagulation, apixaban exerts its phar
macologic effect by binding to free and bound factor Xa in
the body, thus preventing clot formation and platelet activa
tion. Renal excretion accounts for 27%
of apixaban elimination. This makes
apixaban a viable option in patients
with kidney impairment, although
clinical judgment should be employed.
Apixaban is currently approved for risk
reduction of stroke and systemic embo
lism in nonvalvular AF and treatment
of DVT and PE, risk reduction to prevent recurrence of DVT
and PE after initial treatment, and prophylaxis of DVT after
hip or knee replacement surgery.13
Edoxaban
A factor Xa inhibitor, edoxaban was approved by the FDA
in 2015 for nonvalvular AF and is the newest factor Xa
inhibitor to be approved. Like rivaroxaban and apixaban,
it exerts its pharmacologic effect by binding directly to free
and clot-bound factor Xa without requiring cofactors (an
tithrombin), thus preventing thrombus formation and
platelet activation. Currently, edoxaban is indicated for
reduction of stroke and systemic embolism in patients with
nonvalvular AF and treatment of DVT and PE after 5 to 10
days of treatment with a parenteral anticoagulant.14
Consult the manufacturer's prescribing label for com
plete prescribing information including dose recommenda
tions and dose adjustments for each drug.7,11-14
 Reversal agents
Phytonadione (vitamin K)
Vitamin K reverses the anticoagulant effect of warfarin
by promoting hepatic production of the vitamin K-
dependent clotting factors II, VII, IX, and X. By promot
ing hepatic production of the vitamin K-dependent
clotting factors, administering exogenous vitamin K I.V.
or orally expedites the reduction of the international
normalized ratio (INR). Between the two routes of ad
ministration, I.V. vitamin K causes a faster reduction in
the INR within 6 to 8 hours after administration com
pared with oral vitamin K, which causes a reduction
within 24 to 48 hours.15
The reduction in INR achieved after 24 to 48 hours is
similar between the I.V. and oral routes. Therefore, there is
no advantage to using the I.V. route when the need for war
farin reversal is not urgent. The I.M. and subcutaneous
routes of administration are not recommended in patients
requiring warfarin reversal due to erratic absorption; the
10 The Nurse Practitioner -  Vol. 42, No. 11
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Administering vitamin K can result in the
patient being refractory to warfarin when
warfarin is reinitiated.

Copyright (c) 2017 Wolters Kluwer Health, Inc. All rights reserved.
risk of anaphylaxis is a concern when vitamin K is admin
istered via the I.V. route.15,16
The American College of Chest Physicians (ACCP) has
specifi c recommendations that describe when vitamin K
administration is appropriate.16 First, the ACCP recommends
against the routine use of vitamin K for warfarin reversal in
patients with an INR between 4.5 and 10 and no bleeding;
there is no advantage to administering vitamin K in this
situation. Instead, warfarin should be withheld in these
patients until the INR declines. Second, administering oral
vitamin K and withholding warfarin are recommended for
patients with an INR greater than 10 and no bleeding. Fi
nally, in the presence of bleeding regardless of INR, a slow
I.V. dose of vitamin K as well as withholding warfarin are
recommended.15,16
Overall, vitamin K is effective in the complete rever
sal of warfarin within 24 to 48 hours. Per the ACCP, in
tervention with vitamin K is not indicated when the INR
is 10 or less unless the patient has significant bleeding or
requires urgent surgery.16 Administering vitamin K can
result in the patient being refractory to warfarin when
warfarin is reinitiated. Therefore, the
lowest possible dose of vitamin K
should be used to reverse warfarin to
avoid further complications.15
FFP
Prepared from single units of whole
blood or plasma, FFP is a widely used
agent that reverses warfarin in the event of serious bleeding
and elevated INR. Within FFP, all of the clotting factors,
plasma proteins, electrolytes, physiologic anticoagulants
(protein C, protein S, antithrombin, tissue factor pathway
inhibitor), and added anticoagulants exist, allowing FFP to
reverse coagulopathies caused by warfarin.17 Dosing is
based on the patient's weight (10 mL/kg to 20 mL/kg),
which produces a 20% to 30% increase in plasma levels of
clotting factors.15
FFP carries risks, including disease transmission, fl uid
overload, and transfusion reactions, such as hypersensitiv
ity reactions. It must be blood group-specific because it
contains isohemagglutinins. FFP has to be thawed before
use, which could delay treatment in the event of an emer
gency.15 FFP is not effective to reverse the effects of DOACs
and should not be used with reversal of DOACs.10
PCC
PCCs are typically composed of varying amounts of factors
II, VII, IX, and X. Frequently used formulations of PCC
include 3-factor PCC (3-PCC) and 4-factor PCC (4-PCC).
Both products require activation by the clotting cascade to
Reversal agents for oral anticoagulants
exert their effects within the body. PCCs are indicated for
reversal of vitamin K antagonists, such as warfarin.18
The 3-PCC contains the factors II, IX, and X; 4-PCC
contains a combination of coagulation factors II, VII, IX, X,
and proteins C and S. Both of these products are indicated
for patients requiring reversal of vitamin K antagonist due
to acute major bleeding. The administration of PCC causes
thrombotic or thromboembolic events in some patients
treated with PCC. Vitamin K must be administered to pa
tients receiving 4-PCC in order to maintain adequate factor
levels in the body following administration when reversing
warfarin.19
The risk of a thromboembolic event must be weighed
against the risk of acute bleeding in patients receiving
4-PCC. Dosing of 4-PCC is given as a single dose based on
the patient's weight and INR.19
PCCs are currently being studied as potential options
for reversal of DOACs; however, the use of PCCs is cur
rently off-label.18 A meta-analysis by da Luz and colleagues
concluded that PCCs partially reverse DOACs and should
be considered as treatment options in case of severe  bleeding
for DOACs without a reversal agent. Studies for reversal of
DOACs are limited and it is strongly encouraged to look at
risks versus benefit (such as thrombosis) with PCC before
considering using it as a reversal for these agents.20
Idarucizumab
To date, dabigatran is the only DOAC with an FDA-approved
reversal agent. Idarucizumab, a humanized monoclonal
antibody fragment, was approved by the FDA in 2015 as the
reversal agent for dabigatran.21 Due to promising results in
clinical trials, idarucizumab received accelerated approval
from the FDA, which allowed it to come to market sooner
(see Reversal agents for oral anticoagulants).22
Idarucizumab, a humanized monoclonal antibody frag
ment, binds to dabigatran and its metabolites (affi nity ap
proximately 350 times higher than dabigatran for thrombin),
thus neutralizing and reversing dabigatran's anticoagulant
effect.23 Because the mechanism of dabigatran differs from
other DOACs, idarucizumab will only reverse the effects of
dabigatran and should not be used to reverse other DOACs.
Currently, FDA indications of idarucizumab include patients
treated with dabigatran when the reversal of anticoagulant
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Copyright (c) 2017 Wolters Kluwer Health, Inc. All rights reserved.
Reversal agents for oral anticoagulants
effects is warranted for emergency surgery/urgent proce
dures, and/or life-threatening/uncontrolled bleeding.21
Two methods of administration may be used. The fi rst
is a continuous infusion by hanging the vials, and the second
method is providing bolus injections by injecting both vials
consecutively via syringe.21 Once the solution has been
drawn up via syringe for bolus injections, idarucizumab
must be administered within 1 hour. A preexisting I.V. line
may be used for administration, but the line must be fl ushed
with sterile 0.9% sodium chloride injection prior to infu
sion, and no other infusion should be administered via the
same I.V. line.21
Idarucizumab has four warnings that should be con
sidered before administration. First, reversing dabigatran
exposes patients to risk of developing a thrombus due to
the underlying disease (AF). To reduce this risk, restarting
anticoagulation should be considered as soon as medi
cally appropriate, and dabigatran may be reinitiated in a
patient as early as 24 hours after administration of idaru
cizumab.
Second, in a small number of patients in clinical trials,
elevation of coagulation parameters (activated partial
thromboplastin time and/or ecarin clotting time [ECT])
has been observed after the administration of idaruci
zumab (between 12 and 24 hours post administration). If
there is reappearance of clinically relevant bleeding with
elevated coagulation parameters, it may be warranted to
administer another dose of idarucizumab, but the safety
and efficacy of readministration have not been established.21
Third, few reports in clinical trials have noted a hy
persensitivity reaction, and the risk of reaction should
always be considered. However, it is important to always
determine the risk versus benefit when deciding if a
patient should receive idarucizumab. Finally, if patients
with the condition of hereditary fructose intolerance
have had a previous reaction to sorbitol, it is important
to note that idarucizumab contains 4 g of sorbitol as an
excipient and should be considered when administering
idarucizumab.21,22
During the phase III clinical trial, the Reversal Effects
of Idarucizumab on Active Dabigatran (RE-VERSE AD)
study, efficacy and safety of idarucizumab were established.
In the RE-VERSE AD study, patients age 18 or older who
had uncontrollable and/or life-threatening bleeding (group
A) or who required a surgery or other invasive procedures
that could not be delayed for 8 hours (group B) received
idarucizumab. The primary endpoint was the percentage
reversal of the anticoagulant effect of dabigatran, which was
determined within 4 hours after the infusion of idaruci
zumab on the basis of the measurement of dilute thrombin
time (dTT) or ECT by a central lab (dTT and ECT were
chosen as markers of idarucizumab's percentage reversal
Reversal agents for oral anticoagulants1,15,18,19,23,27
Anticoagulant
Reversal agent
Mechanism of action
Warfarin
Vitamin K
Cofactor for hepatic synthesis
of factors II, VII, IX, and X
FFP
Repletes all plasma proteins
and clotting factors
3-PCC
Repletes vitamin K-dependent
clotting factors II, IX, and X
4-PCC
Repletes vitamin K-dependent
clotting factors II, VII, IX, X as
well as proteins C and S
Dabigatran
Idarucizumab
Binds to and reverses dabiga
tran and its metabolites
Rivaroxaban
Andexanet alfa
Binds to and reverses effects
of factor Xa inhibitors
Apixaban
Edoxaban
Important facts
Recommended when a patient is bleeding or
has an INR >10
May transmit diseases; must be blood type-
specifc because FFP contains isohemaggluti
nins; may cause fuid overload, which could be
problematic in patients with heart failure
Must coadminister vitamin K with dose; some
products contain heparin and are contraindi
cated in patients with heparin-induced throm
bocytopenia (HIT); refer to package insert for
dosing, as this depends on the product
Dose is determined by the patient's predose
INR and body weight; must coadminister vita
min K with dose; preferred over FFP in cases
of major bleeding; contains heparin and is
contraindicated in patients with HIT
Must administer both vials in package for com
plete reversal of dabigatran
Currently in phase III clinical trials and pending
FDA approval
12 The Nurse Practitioner -  Vol. 42, No. 11
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Copyright (c) 2017 Wolters Kluwer Health, Inc. All rights reserved.
effect because these markers are highly correlated with the
concentrations of unbound dabigatran). Of note, dTT and
ECT may not be readily available. Many different secondary
endpoints were evaluated, but the major secondary endpoint
was hemostasis restoration.23
To provide idarucizumab to patients as soon as possible,
an interim analysis from the RE-VERSE AD study was pub
lished in June 2015. Overall, idarucizumab completely re
versed the anticoagulant effect of dabigatran in 90 patients
within minutes of administration. Among the 68 patients
who had elevated dTT and 81 who had elevated ECT, the
medium maximum percentage reversal was 100% (95%
confidence interval [CI], 100 to 100), which was evident on
the first sample taken after the first infusion of idaruci
zumab. Therefore, since the interim results indicated that
idarucizumab was an effective reversal agent for dabigatran,
idarucizumab received accelerated approval from the FDA
in October 2015, which was contingent upon the results of
the full cohort analysis.23
In August 2017, the full cohort analysis of the RE
VERSE AD study was published, which continued to show
that idarucizumab was an effective and safe reversal agent
for dabigatran. Among the 503 patients in the trial, 461
patients (91.7%, 276 in group A and 185 in group B) had
an elevated ECT or a prolonged dTT at study entry. With
in 4 hours after administering idarucizumab, 100% (95%
CI 100 to 100) of dabigatran's anticoagulant effect was
reversed based on the ECT and dTT measurement. Fur
thermore, unbound (active) dabigatran concentrations
remained less than 20 ng/mL (a level that produces little or
no anticoagulant effect) for the majority of patients for 24
hours. Of note, reemergence of levels greater than 20 ng/
mL occurred in 114 of 497 patients (23%), but only 10
patients experienced recurrent or continuous bleeding.
Regarding restoration of hemostasis, in group A, 134 pa
tients (98 patients had intracranial bleeding and could not
be assessed) had confi rmed bleeding cessation within 24
hours, and the median investigator-reported time to ces
sation of bleeding was 2.5 hours.
In group B, 197 patients underwent urgent procedures,
and normal intraoperative hemostasis was reported in 184
patients (93.4%). Regarding safety, 117 patients (23.3%;
66 in group A and 51 in group B) had serious adverse
events within 5 days of idarucizumab administration.
However, no consistent pattern developed, and the major
ity of events were due to worsening of their underlying
conditions.24
 Andexanet alfa
Patients taking factor Xa inhibitor anticoagulants are at an
increased risk of bleeding in emergency situations, such as
Reversal agents for oral anticoagulants
trauma or surgery. Currently, there are no approved agents
for the reversal of factor Xa inhibitors. Andexanet alfa is a
new agent seeking FDA approval that completely reverses
direct and indirect factor Xa inhibitors, such as rivaroxaban,
apixaban, edoxaban, and enoxaparin.25
Andexanet alfa is a recombinant modified human factor
Xa decoy protein, which exerts its effects by binding to factor
Xa inhibitors and preventing their anticoagulant effects
within the body. Administration in clinical trials has in
cluded a bolus dose followed by a 2-hour infusion of andex
anet alfa. Because andexanet alfa has not yet been approved
for use, the dosing and administration information have not
been established.25
Andexanet alfa is currently undergoing a third phase
III clinical trial to test its effectiveness in the reversal of
these agents in direct and indirect factor Xa inhibitors.
Two additional phase III trials showing the efficacy of
andexanet alfa have already been completed. The AN
NEXA-A trial only tested the reversal agent's effectiveness
in apixaban, whereas the ANNEXA-R trial showed its
effectiveness when reversing rivaroxaban.26 The apixaban
and rivaroxaban trials did not report any thromboem
bolic events caused by the  administration of the reversal
agent.26
One patient was reported to have an anaphylactic reac
tion upon administration.26 While the last phase III trial
has not yet been completed, a preliminary analysis has been
recently published. This analysis reported andexanet alfa
to be effective in the rapid reversal of factor Xa agents in
67 patients. However, 12 of the 67 patients (18%) reported
having thrombotic events after being treated with andex
anet alfa.25
 Conclusion
Prescribing of DOACs is on the rise due to their effi cacy and
safety that has been seen in many clinical studies, and the
need for effective antidotes is warranted. Currently, the only
FDA-approved reversal agent for a DOAC is idarucizumab
for dabigatran, which leaves the factor Xa inhibitors rivar
oxaban, apixaban, and edoxaban without effective reversal
agents. However, andexanet alfa has shown efficacy in the
reversal of factor Xa inhibitors and is currently in phase III
clinical trials.27
REFERENCES
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2. Odum LE, Cochran KA, Aistrope DS, Snella KA. The CHADS2 versus the
new CHAD2DS2-VASc scoring systems for guiding antithrombotic treatment
of patients with atrial fibrillation: review of the literature and recommenda
tions for use. Pharmacotherapy. 2012;32(3):285-296.
3. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in
patients with atrial fi brillation. N Engl J Med. 2009;361(12):1139-1151.
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The Nurse Practitioner -  November 2017  13

Page 7
Copyright (c) 2017 Wolters Kluwer Health, Inc. All rights reserved.
Reversal agents for oral anticoagulants
4. The Einstein Investigators. Oral rivaroxaban for systemic venous thrombo-
embolism. N Engl J Med. 2010;363:2499-2510.
5. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in
patients with atrial fi brillation. N Engl J Med. 2011;365(11):981-992.
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patients with atrial fi brillation. N Engl J Med. 2013;369(22):2093-2104.
 7. Coumadin(R) (warfarin sodium) oral tablets [package insert]. Princeton, NJ:
Bristol-Myers Squibb Company; 2017.
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complex concentrates in reversing warfarin anticoagulation: a review of the
literature. Am J Hematol. 2008;83(2):137-143.
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ambulatory oral anticoagulant use. Am J Med. 2015;128(12):1300-1305.e2.
10. Tummala R, Kavtaradze A, Gupta A, Ghosh RK. Specific antidotes against
direct oral anticoagulants: a comprehensive review of clinical trials data.
Int J Cardiol. 2016;214:292-298.
11. Pradaxa(R) (dabigatran etexilate mesylate) oral capsules [package insert].
Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2017.
12. Xarelto(R) (rivaroxaban) oral tablets [package insert]. Titusville, NJ: Janssen
Pharmaceuticals, Inc.; 2017.
13. Eliquis(R) (apixaban) oral tablets [package insert]. Princeton, NJ: Bristol-
Myers Squibb; 2017.
14. Savaysa(R) (edoxaban) oral tablets [package insert]. Parsippany, NJ: Daiichi
Sankyo, Inc.; 2016.
15. Kalus JS. Pharmacologic interventions for reversing the effects of oral
 anticoagulants. Am J Health Syst Pharm. 2013;70(10 suppl 1):S12-S21.
16. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of
anticoagulant therapy: antithrombotic therapy and prevention of throm-
bosis, 9th ed: American College of Chest Physicians evidence-based clinical
practice guidelines. Chest. 2012;141(suppl 2):e152S-e184S.
17. Nascimento B, Callum J, Rubenfeld G, et al. Clinical review: fresh frozen
plasma in massive bleedings-more questions than answers. Crit Care.
2010;14(1):202.
18. Babilonia K, Trujillo T. The role of prothrombin complex concentrates
in reversal of target specifi c anticoagulants. Thromb J. 2014;12:8.
INSTRUCTIONS
Reversal agents for oral anticoagulants
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19. Kcentra(R) (prothrombin complex concentrate [human]) injection for intra
venous use [package insert]. Marburg, Germany: CLS Behring GmbH; 2013.
20. da Luz LT, Marchand M, Nascimento B, Tien H, Nathens A, Shah P. Effi cacy
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Carrie L. Griffiths is an  of pharmacy at Wingate University
School of Pharmacy, Wingate, N.C.
Mark L. Vestal is a fourth-year doctor of pharmacy candidate at Wingate
University School of Pharmacy, Wingate, N.C.
Spencer J. Livengood is a fourth-year doctor of pharmacy candidate at
Wingate University School of Pharmacy, Wingate, N.C.
Samantha Hicks is the chief acute care NP, Pulmonary Critical Care Medicine at
Carolinas Medical Center-Main, Charlotte, N.C.
The authors and planners have disclosed no potential conflicts of interest,
financial or otherwise.
DOI-10.1097/01.NPR.0000525714.86663.bd
14 The Nurse Practitioner -  Vol. 42, No. 11
www.tnpj.com