Download Anticoagulation Antidote Guide

Anticoagulation Antidote Guide for Harris/Swain
The purpose of this guide is to formalize the process for reversal of anticoagulation in major bleeding or if patient
requires emergent surgery. In addition to attempts to reverse anticoagulation, supportive care including fluid
resuscitation, source identification, and treatment at the site of bleeding are critical in the management of
anticoagulation related bleeds.
Definition of major bleeding: fatal or life threatening bleeding, symptomatic bleeding in a critical area or organ, or
bleeding causing a drop in hemoglobin of 2 g/dL or requiring blood transfusion
DRUG
CLASS
DRUG
NAME
apixaban
(Eliquis)
HALF-LIFE AND
ELIMINATION
ROUTES
LAB TESTS TO
MONITOR
~12 hours
PT, aPTT, and anti
factor Xa assay
may help guide
clinical decisions

PT, aPTT, and anti
factor Xa assay
may help guide
clinical decisions

Mainly hepatic with
27% renal
edoxaban
(Savaysa)
10-14 hours
50% renal-
Factor Xa
Inhibitors
rivaroxaban
(Xarelto)
Healthy: 5-9 hours
Elderly: 11-13 hrs
(longer in renal
impairment)
Anti-factor Xa
36% renal
dabigatran
(Pradaxa)
12-17 hours
(up to 28 hours in
severe renal
impairment)
Direct
thrombin
Inhibitor
aPTT or plasma
diluted thrombin
time (sent out to
lab corp)
STRATEGIES TO REVERSE DRUG


If ingested within 2 hours, administer
activated charcoal.
Not removed by HD
Consider off label use of 4-factor PCC
(KCentra) for life threatening bleeds
(max dose 5000 units)
If ingested within 2 hours, administer
activated charcoal
 Consider off label use of Kcentra for life
threatening bleeds (max dose 5000
units)
 Only 25% removed by HD (not clinically
significant)
NOTES: PCC may partially correct PT/aPTT
but will not affect anti-factor Xa activity or
increase drug clearance, correlation with
reduction in bleeding is unknown
 If ingested within 2 hours, administer
activated charcoal
 Consider off label use of KCentra for life
threatening bleeds (max dose 5000
units)
 Not removed by HD
NOTES: PCC may partially correct PT/aPTT
but will not affect anti-factor Xa activity or
increase drug clearance, correlation with
reduction in bleeding is unknown
 If ingested within 2 hours, administer
activated charcoal
 For life threatening bleed or emergency
surgery, consider idarucizumab
(Praxbind) 5 gm IV (non-formulary drug
at Harris/Swain)
 65% removed by HD
NOTES: Plasma dabigatran concentrations
can increase more than 12-24 hours after
administration due to re-distribution. The
aPTT and plasma-diluted thrombin time will
argatroban
40-50 minutes
Hepatic
aPTT
Low
molecular
weight
heparin
enoxaparin
(Lovenox)
3-7 hours
Anti factor Xa
UFH
Heparin
30-90 minutes
(dose dependant)
Vitamin K
Antagonist
warfarin
(Coumadin)
20-60 hours
(Anti factor Xa
exposure is increased
in renal impairment)
Hepatic
INR
<5
>5 but < 9
>9
Rapid reversal
needed for surgery
likely correct but correlation with improved
outcomes have not been established.
 Turn off infusion
 20% removed by HD (not clinically
significant)

Can use protamine for partial
neutralization (60-80%)
Time since
Dose of protamine for each
last dose
1 mg of enoxaparin
<8 hours
1 mg ( or fixed 50 mg dose)
8-12 hours
0.5 mg (or fixed 25 mg dose)
>12 hours
Not likely useful
PTT and anti
 Use protamine for heparin
factor Xa activity
neutralization (100%)
 Partially removed by HD
 Max single dose of protamine is 50mg
Time since last
Dose of protamine for
dose of Heparin
each 100 units of heparin
Immediate
1 mg
30 minutes- 2
0.5 mg
hours
>2 hours
0.25 mg
NOTE: For SC heparin reversal, Give 25mg
bolus, then infuse remaining dose over 8 hours.
PT/INR
 May take 3-7 days for INR to normalize
 Oral Vitamin K is preferred for patients
without serious bleeding
 Subcutaneous or intramuscular doses
are not recommended.
NO BLEEDING
BLEEDING OR HIGH
BLEEDING RISK
 Lower dose or omit next
 Omit next dose. Monitor
dose. Monitor INR more
INR more frequently
frequently
 Vitamin K 1-2mg IV over
30 minutes if clinically
relevant OR
 Vitamin K 2.5mg PO
once
 Omit next one to three
 Omit next one to three
warfarin doses. Monitor
doses. Monitor INR
INR more frequently
more frequently
 Consider giving Vitamin
 Give Vitamin K 2 – 5 mg
K 2.5 to 5mg PO once
IV over 30 minutes once
if clinically relevant.
 Hold warfarin until INR
 Hold warfarin until INR
at goal.
at goal
 Consider giving Vitamin
 Give Vitamin K 2.5-5mg
K 5mg PO once
IV once over 30 minutes
 Hold warfarin

Life threatening
bleed (any INR) or
surgery requiring
emergent warfarin
reversal
Vitamin K 2-5 mg by slow IV infusion over 30 minutes if
reversal needed in 12 hours
 Vitamin K 5-10 mg PO once if reversal needed in 24-48 hrs
 Hold Warfarin and give Vitamin K 10mg IV once over 30
minutes along with Kcentra (see protocol).
INR
KCENTRA DOSE
1.5-3.9
25 units/kg (max 2500 units)
4-6
35 units/kg (max 3500 units)
>6
50 units/kg (max 5000 units)

Consider FFP if not able to use Kcentra due to
contraindications (such as DIC or heparin allergy) or patient
specific circumstances.
ANTIPLATELET AGENTS
Drug Class
Agent
Salicylate
Aspirin
Time to Maximum
Antiplatelet Effect
30 min
Elimination
Half-Life
15-30 min
Notes
Antiplatelet effects begin within one
hour of dose and persist for at least 4
days after stopping therapy.
ADP Receptor
Clopidogrel
3-7 days
8 hours
More rapid inhibition of platelet
Antagonists
(Plavix)
function is achieved with loading doses;
antiplatelet effect lasts up to 10 days
after stopping therapy.
Prasugrel
30 min
7 hours
Antiplatelet effect lasts 5-7 days after
(Effient)
stopping therapy.
Ticagrelor
1.5 hours
7 hours
Antiplatelet effects are decreased to
(Brilinta)
30% activity after 2.5 days.
Ticlopidine
1-3 hours
24-36 hours
Antiplatelet effect lasts 5-7 days after
(Ticlid)
stopping therapy.
Table adapted from Ortel TL. Blood 2012 Dec 6; 120(24):4699-705.
 Antiplatelet agents that irreversibly inhibit platelet function: aspirin, clopidrogel, prasugrel
 Antiplatelet agents that reversibly inhibit platelet function: dipyridamole, NSAIDs, ticagrelor