Anticoagulation Reversal Agents

Reversal Agent

Protamine

Anticoagul
ant that is
reversed
Heparin

Protamine

Enoxaparin
(Lovenox)

Phytonadione/
Vitamin K (VK)
(Mephyton)

Warfarin
(Coumadin)

Mechanism
of action of
Reversal
Agent
Combines with
heparin to
form stable
complex
neutralizing
anticoagulatio
n1

Combines with
LMWH to
neutralize
anticoagulatio
n. Anti Xa
activity is
never
completely
neutralized
(max 60%)3
Stimulates
hepatic
production of
clotting
factors IIa, IVa,
IXa, Xa

Administration of
Reversal Agent

Time Dependent dosing

(Max dose 50mg)
Time Elapsed
Immediate

Dose/100
u
1-1.5mg

30-60min

0.50.75mg

>2hr

0.250.375mg

Dabigatran
(Pradaxa)

It is a
humanized
monoclonal
antibody
fragment that
specifically

Protamines half-life
of elimination is 7
minutes.1
Anticoagulation reinitiation may be
considered as
clinically indicated.
Protamine may
cause platelet
inhibition, and
heparin rebound.2

Time Dependent Dosing

Time Elapsed
Dose/1m
g
<8h
1mg
>8h
0.5mg

See above.

INR >10 (no bleeding):

2.5-5mg PO VK4

Warfarin may be
resumed once
bleeding has
stopped and its
cause corrected.
Phytonadione is
widely distributed in
tissues and has a
long but variable
half-life. This may
increase the amount
of time necessary
for achievement of
therapeutic INR.5
Dabigatran
treatment can be
initiated 24 hours
after administration
of PRAXBIND or as
soon as medically

Minor bleed , any INR: 2.55mg PO VK4

Major bleed, any INR:
Kcentra + 5-10mg VK4

Idarucizumab
(Praxbind)

After Reversal
Agent
Administration

Two consecutive 2.5g IV

infusions (<15 min apart)
(Total dose 5g) 7

binds free and

thrombinbound
dabigatran
with higher
affinity than
the binding
affinity of
dabigatran to
thrombin,
neutralizing
anticoagulatio
n within
minutes.6

appropriate to
reduce risk of clot.7

Side Effects

Protamine: low BP, decreased HR, flushing, nausea, vomiting, bleeding, pulmonary
hypertension
Phytonadione: cyanosis, flushing, dizziness, itchiness, abnormal taste, shortness of
breath
Praxbind: delirium, headache, low K+, pneumonia, fever, constipation

As of 08/12/16, there is no reversal agent on the market for the following agents:

Apixaban (Eliquis)
Rivaroxaban (Xarelto)
Edoxaban (Savaysa)
Fondaparinux (Arixtra)

Note: Kcentra may be administered if bleed occurs on apixaban, rivaroxaban, or edoxaban

(50units/kg, max 5000 units). Kcentra will partially affect PT/aPTT, but will not correct anti-Xa
activity.8
Note: If bleed occurs on fondaparinux (Arixtra), administration of rFVIIa (Novoseven) at
90mcg/kg may be considered, but will not correct anti-Xa activity. 8
Pipeline

Andexanet alfa: Recombinant protein specifically designed to reverse the

anticoagulant activity of both direct and indirect Factor Xa inhibitors.

Works Cited
1. Lexicomp [Internet]. Lexicomponline.com. [cited 2016 Aug 10]. Available from:
http://www.lexicomponline.com
2. Mochizuki T, Olson P, Szlam F, Ramsay J, Levy J. Protamine Reversal of Heparin
Affects Platelet Aggregation and Activated Clotting Time After Cardiopulmonary
Bypass. Anesthesia & Analgesia. 1998;87(4):781-785.

3. Lovenox (enoxaparin sodium injection) for subcutaneous and intravenous use

Prescribing Information [Internet]. Products.sanofi.us. 2013 [cited 2016 Aug 10].
Available from: http://products.sanofi.us/lovenox/lovenox.html
4. Volume 141 Issue 2_suppl | CHEST Journal | CHEST Publications [Internet].
Journal.publications.chestnet.org. 2012 [cited 2016 Aug 10]. Available from:
http://journal.publications.chestnet.org/issue.aspx?issueid=23443
5. Hirsh J. American Heart Association/American College of Cardiology Foundation Guide
to Warfarin Therapy. Circulation. 2003;107(12):1692-1711.
6. Nichols EPollack C. RE-VERSE AD: Idarucizumab Safe, Effective for Dabigatran
Reversal. MD Conference Express. 2015;15(21):4-5.
7. Praxbind Package Insert [Internet]. Accessdata.fda.gov. [cited 2016 Aug 10]. Available
from: http://www.accessdata.fda.gov
8. Guidelines for Reversal of Anticoagulants | Anticoagulation Services [Internet].
Depts.washington.edu. 2016 [cited 2016 Aug 10]. Available from:
https://depts.washington.edu/anticoag/home/content/guidelines-reversalanticoagulants