500-56, Attachment C
Anticoagulant & Antiplatelet Reversal/Rescue Guidelines, revised 11/2015
The recommendations below are guidelines and require a licensed independent practitioner order.
Section I:
Section III:
Coumadin (warfarin) Reversal Guidelines
IV/SQ Anticoagulant Reversal Guidelines
Section I:
Coumadin (warfarin) Reversal Guidelines
Section II: Oral Anticoagulant Reversal Guidelines
Section IV: Antiplatelet & Fibrinolytic Reversal Guidelines
Clinical Pharmacist may change Vitamin K IV, IM or SQ to oral if the patient can tolerate oral medications using these
guidelines below. Orders will be signed “Per Policy” (See Route Change Policy 7300-VII-50)
INR
Symptoms
2-3.5
Surgery/Procedure:
 Scheduled
Recommendations:

Stop warfarin 4-5 days prior to surgery and begin heparin or
LMWH as indicated by disease state.

Urgent (24-48hrs)

Stop warfarin, and give Vitamin K 2.5- 5 mg po. May repeat
Vitamin K 1-2mg orally if INR is still elevated.

Emergency (< 24 hrs)

Reverse warfarin with Vitamin K 2.5-5 mg IV or orally. For
more immediate reversal, give FFP plus Vitamin K 2.5-5 mg IV
or orally.

MAX Vit K 10 mg IV x 1 dose. If INR still elevated after 12
hrs, may repeat Vit K 10 mg IV dose.
3.5 to <5

No bleeding

Omit next dose and/or resume at a lower dose when the INR is
at therapeutic level
>5-9

No significant bleeding


Omit next 1-2 doses and resume at lower doses when INR in
therapeutic range OR
Omit dose and give Vitamin K 1 – 2.5mg orally if patient is at
increased risk of bleeding.
>9

No significant bleeding


Hold warfarin, give Vitamin K 2.5 – 5 mg orally.
Resume at lower doses when INR in therapeutic range.
At any
elevation of
INR

Serious bleeding or
major warfarin
overdose

Hold warfarin therapy and give Vitamin K 10mg slow IV
infusion (may repeat in 12 hours for persistent INR elevation) and
FFP (or prothrombin complex concentrate depending on the
urgency of the situation. Factor VIIa may be considered as an
alternative to prothrombin complex concentrate)
At any
elevation of
INR

Life-threatening
bleeding



Hold warfarin therapy
Vitamin K 10 mg IV in 50 ml NS over 30 minutes PLUS
Prothrombin Complex Concentrate (Kcentra, 4-Factor, seq #
35127)
May repeat vitamin K 5-10mg
IVPB q12hrs until INR < 1.4
(PO time to effect = 24 hrs)
(IV time to effect = 12 hrs)
INR < 2 – 4: 25 units/kg (max dose 2,500 units) IVPB at < 8ml/min.
INR 4 – 6: 35 units/kg (max dose 3,500 units) IVPB at < 8ml/min.
INR > 6: 50 units/kg (max dose 5,000 units) IVPB at < 8ml/min.
***Recheck INR 30 Min after infusion completed. If bleeding continues,
consider cryoprecipitate for fibrinogen < 100mg/ml, FFP, or platelet
transfusion. ***
OR
Vitamin K 10 mg IV in 50 ml NS over 30 minutes.
+
NovoSeven (FVIIa) 15-30 mcg/kg x 1 (half-life ~ 2 hours) + FFP
Page 1 of 6
500-56, Attachment C
Section II:
Oral Anticoagulant Reversal Guidelines
The recommendations below are guidelines and require a licensed independent practitioner order.
Drug
Reversal Agent
Eliquis
(apixaban)
None
Interventions for Severe or
Life-threatening Bleeding
Charcoal < 6 hours ingestion
The following may be of value but
NO/limited human evidence
Prothrombin Complex Concentrate
(Kcentra, 4-Factor, seq # 35127)
50 units/kg IVPB (max dose 5,000 units) at
0.12 ml/kg/min (max 8 ml/min).
Effect should be seen in < 30 minutes
OR
NovoSeven (Factor VIIa) 2 mg < 100 kg, 4 mg >
100 kg IV bolus over 3-5 minutes. Effect should be
seen in < 30 minutes. May repeat in 2 hours if
bleeding continues.
Pradaxa
(dabigatran)
Class:
Direct Thrombin
Inhibitor
Praxbind (idarucizumab)
5 gm
(2 vials, each contains
2.5 gm/50 ml)
IVP over 5 minutes
May repeat dose after 12-24 hrs only
if the following 2 criteria are met:
PTT is elevated
AND
patient is still experiencing lifethreatening bleeding
Charcoal if < 2 hr of ingestion
The following may be of value but
NO/limited human evidence:
Factor VIIa 2 mg if < 100 kg, 4 mg if > 100 kg IV
push over 3-5 minutes x 1, may repeat in 2 hrs if
bleeding continues.
OR
Prothrombin Complex Concentrate
(Kcentra, 4-Factor, seq # 35127)
50 unit/kg IVPB (max dose 5,000 units) at
0.12 ml/kg/min (max 8 ml/min)
Anticoagulant effect is through direct clotting factor
inhibition and not clotting factor depletion, therefore
FFP/PCC/Factor VII is not anticipated to be wholly
effective in reversing.
Protamine and Vit K have no effect.
Give platelets if thrombocytopenia present or if long
acting antiplatelets drug have also been used.
Xarelto
(Rivaroxaban)
Class:
Xa Inhibitor
None
Charcoal < 2 hours ingestion
The following may be of value but
NO/limited human evidence
Prothrombin Complex Concentrate
(Kcentra, 4-Factor, seq # 35127)
50 units/kg IVPB (max dose 5,000 units) at
0.12 ml/kg/min (max 8 ml/min).
Effect should be seen in < 30 minutes
OR
Factor VIIa 2 mg < 100 kg, 4 mg > 100 kg IV bolus
over 3-5 minutes. Effect should be seen in < 30
minutes. May repeat in 2 hours if bleeding continues.
Lab
PT lab value is not
of clinical utility in
measuring adequate
anti-coagulation but
has qualitative value
for situations such
as in severe
overdose or
evaluation of
compliance.
aPTT
(normal value
suggests little or
no anticoagulant
activity) (max of
2X control)
or
TT (too sensitive
but of qualitative
value, normal
value suggests
little or no
anticoagulant
activity)
ECT is a sensitive
measure with direct
linear correlation but
not commercially
available.
PT lab value is not
of clinical utility in
measuring adequate
anti-coagulation but
has qualitative value
for situations such
as in severe
overdose or
evaluation of
compliance.
Page 2 of 6
500-56, Attachment C
Section III: IV/SQ Anticoagulant Reversal Guidelines
The recommendations below are guidelines and require a licensed independent practitioner order.
Drug
Reversal Agent
Angiomax
(bivalirudin)
None
Class:
Direct Thrombin
Inhibitor
Interventions for Severe or
Life-threatening Bleeding
Discontinue infusion.
Anticoagulation parameters generally return to
baseline quickly at 1 hr
Fibrinogen in the form of FFP or cryoprecipitate can
be given to work as a competitor to displace
bivalirudin from thrombin.
Lab/Comments
Monitor ACT
Short half-life and
discontinuation are
primary means of
attenuating bleed –
support with
crystalloid and blood
products to facilitate
rapid renal clearance.
Amicar (aminocaproic acid) 5 gm in 250 ml NS IV
over 1 hour then 5 gm/250ml NS at 50 ml/hr infusion
can be used until bleeding ceases
Argatroban
None
Class:
Direct Thrombin
Inhibitor
Arixtra
(fondaparinux)
Class:
Xa Inhibitor
Discontinue infusion
Anticoagulation parameters generally return to
baseline quickly at 2-4 hrs.
Factor VIIa 2 mg < 100 kg, 4 mg > 100 kg IV bolus
over 3-5 minutes. Effect should be seen in < 30
minutes. May repeat in 2 hours if bleeding continues.
Limited human evidence.
May be of value but use as last resort.
None
Monitor PTT.
Short half-life and
discontinuation are
primary means of
attenuating bleed –
support with
crystalloid and blood
products to facilitate
rapid renal clearance.
Administration of rVIIa and PCCs has been shown to
reverse the anticoagulation effects of fondaparinux in
small studies and may be considered as an option.
Factor VIIa 2 mg < 100 kg, 4 mg > 100 kg IV bolus
over 3-5 minutes. Effect should be seen in < 30
minutes. May repeat in 2 hours if bleeding continues.
OR
Prothrombin Complex Concentrate
(Kcentra, 4-Factor, seq # 35127)
50 units/kg IVPB infused at 0.12ml/kg/min (max
8 ml/min).
Effects should be seen in < 30 minutes.
Page 3 of 6
500-56, Attachment C
Drug
Reversal Agent
Heparin
Protamine
(max dose 50 mg)
Heparin IV bolus:
 < 30 min: Protamine 1-1.5
mg per 100 units heparin
administered
 30-60 min: Protamine 0.50.75 mg per 100 units
heparin administered
 1-2 hrs: Protamine 0.3750.5 mg per 100 units heparin
administered
 2 hrs: Protamine 0.25-0.375
mg per 100 units heparin
administered
Heparin Infusion:
 Protamine 1 mg per 100
units heparin administered
over last 4 hours
Heparin SQ:
 Protamine 1-1.5 mg per 100
units heparin administered
Protamine (partial reversal)
max dose 50 mg
Within 8 hrs of last dose:
Protamine 1 mg per 1mg
LMWH. May repeat 2-4 hrs
prn with Protamine 0.5 mg
per 1mg LMWH
8-12 hrs of last dose:
Protamine 0.5 mg per 1 mg
LMWH
> 12 hrs of last dose: None
LMWH
Low Molecular
Weight Heparin:
Lovenox
(enoxaparin)
Fragmin
(dalteparin)
Interventions for Severe or
Life-threatening Bleeding
Lab/Comments
Protamine IV administration:
Slow IV push at 5mg/min with
max of 50 mg per dose.
Recheck
anti-Xa Heparin
level 15 minutes
post dose to
assess response.
Anti-Xa level
Protamine IV administration:
Slow IV push at 5mg/min with
max of 50 mg per dose.
Page 4 of 6
500-56, Attachment C
Section IV: Antiplatelet & Fibrinolytic Reversal Guidelines
The recommendations below are guidelines and require a licensed independent practitioner order.
Drug
Reversal Agent
Activase/TNK
(alteplase/
tenecteplase)
None
None
Class:
Cox 1 and 2
inhibitor
Brilinta
(ticagrelor)
Platelet transfusion
May consider DDAVP (desmopressin) 0.3 mcg/kg
administered over 15 min to augment platelet function
in addition to platelet transfusion.
(serial doses associated with tachyphylaxis,
hyponatremia, and seizures)
None
Class:
Reversible ADPreceptor
antagonist
Effient
(prasugrel)
Lab/Comments
Fibrinogen
If bleeding continues consider:
Platelet infusion
Amicar (aminocaproic acid) 5 gm in 250 ml NS IV
over 1 hour then 5 gm/250ml NS at 50 ml/hr infusion
until bleeding ceases
Class:
Fibrinolytic
Aspirin
Interventions for Severe or
Life-threatening Bleeding
Cryoprecipitate 8-12 units +
FFP (fresh frozen plasma) 2 units +
Protamine (if heparin administration)
No data exist with BRILINTA regarding a
hemostatic benefit of platelet transfusions.
Brilinta is a reversible inhibitor and platelet
function normalizes after drug clearance. Circulating
Brilinta may inhibit transfused platelets.
Salicylate level
or
Platelet inhibition
test
Plavix Inhibition
test
(goal platelet
function
inhibition < 20%)
Amicar (aminocaproic acid) 100 mg/kg IV
(max 5 gm dose) over 30-60 min, then maintenance
oral or IV: 1-4 gm q 4-8 hrs or 1 gm/hr until
hemostasis achieved with max daily dose 24 gm
or
FVIIa 15-30 mcg/kg IV push over 3-5 minutes
x 1, may repeat in 2 hours if bleeding continues
or
May consider DDAVP (desmopressin) 0.3 mcg/kg
administered over 15 min to augment platelet function
May be ineffective if Plavix inhibition test
(Verify Now) is < 20%
(serial doses associated with tachyphylaxis,
hyponatremia, and seizures)
None
Platelet transfusion
(may require 2-3 plateletpheresis to reverse Effient
induced platelet disaggregation)
May consider DDAVP (desmopressin) 0.3 mcg/kg
administered over 15 min to augment platelet function
in addition to platelet transfuion.
May be ineffective if Plavix inhibition test
(Verify Now) is < 20%
(serial doses associated with tachyphylaxis,
hyponatremia, and seizures)
Plavix Inhibition
Test
(goal platelet
function
inhibition < 20%)
Page 5 of 6
500-56, Attachment C
Drug
Reversal Agent
Aggrastat
(tirofiban)
None
Class:
GP-IIaIIIb
Inhibitor
Plavix
(clopidogrel)
Class:
ADP-receptor
antagonist
Interventions for Severe or
Life-threatening Bleeding
Discontinue infusion
(Normal platelet function resumes 4-6 hrs
after holding Aggrestat)
Platelet transfusion only with thrombocytopenia
May consider DDAVP (desmopressin) 0.3 mcg/kg
administered over 15 min to augment platelet function
(serial doses associated with tachyphylaxis,
hyponatremia, and seizures)
None
Platelet transfusion
(may require 2-3 plateletpheresis to reverse Plavix
induced platelet disaggregation)
May consider DDAVP (desmopressin) 0.3 mcg/kg
administered over 15 min to augment platelet function
in addition to platelet transfusion.
May be ineffective if Plavix inhibition test
(Verify Now) is < 20%
(serial doses associated with tachyphylaxis,
hyponatremia, and seizures)
Lab/Comments
None
Short half-life and
discontinuation are
primary means of
attenuating bleed –
support with
crystalloid and blood
products to facilitate
rapid renal clearance
Plavix Inhibition
test
(goal platelet
function
inhibition < 20%)
OR
FVIIa 10-20 mcg/kg IV push over 3-5 min x 1,
may repeat in 2 hours if bleeding continues
Ticlid
(ticlopidine)
Class:
ADP-receptor
antagonist
None
Platelet transfusion
May consider DDAVP (desmopressin) 0.3 mcg/kg
administered over 15 min to augment platelet function
in addition to platelet transfusion.
May be ineffective if Plavix inhibition test
(Verify Now) is < 20%
(serial doses associated with tachyphylaxis,
hyponatremia, and seizures)
Plavix Inhibition
test
(goal platelet
function
inhibition < 20%)
Page 6 of 6