Title of Guideline

Contact Name and Job Title (author)

Guideline for patients receiving Apixaban

(Eliquis) requiring Emergency Surgery or
treatment for Haemorrhage
Julian Holmes (Haemostasis and
Thrombosis Pharmacist)

Directorate & Speciality

Diagnostics and Clinical Support

Date of submission

November 2013

Date on which guideline must be reviewed (this should be

one to three years)
Explicit definition of patient group to which it applies (e.g.
inclusion and exclusion criteria, diagnosis)

November 2015

Abstract

Contains information on the following:

Measuring anticoagulant effect of apixaban
Withholding apixaban for invasive
procedures
Reversal and overdose
Emergency surgery and haemorrhage

Key Words

Apixaban, emergency, surgery, atrial

fibrillation, warfarin, haemorrhage, bleeding,
octaplex, tranexamic acid

Statement of the evidence base of the guideline has the

guideline been peer reviewed by colleagues?

1b, 4

Evidence base: (1-5)

1a

meta analysis of randomised controlled trials

1b

at least one randomised controlled trial

2a

at least one well-designed controlled study without

randomisation
at least one other type of well-designed quasiexperimental study
well designed non-experimental descriptive studies
(ie comparative / correlation and case studies)
expert committee reports or opinions and / or clinical
experiences of respected authorities
recommended best practise based on the clinical
experience of the guideline developer

2b
3
4
5

Adult patients receiving apixaban requiring

emergency surgery or treatment of
haemorrhage

Based on the Aristotle trial of warfarin vs

apixaban for SPAF
NICE TA 275
SPC for apixaban
BCSH guideline Effect on routine
coagulation screens and assessment of
anticoagulation intensity in patient taking
oral dabigatran or rivaroxaban

Consultation Process

Haemostasis and Thrombosis Service

Drugs and Therapeutics Committee
Anaesthetics

Target audience

All wards and clinical areas

This guideline has been registered with the trust.

However, clinical guidelines are guidelines only. The
interpretation and application of clinical guidelines will
remain the responsibility of the individual clinician. If
in doubt contact a senior colleague or expert. Caution
is advised when using guidelines after the review date.
1

Protocol for patients receiving Apixaban (Eliquis) requiring an invasive

procedure, emergency surgery or treatment for haemorrhage
Contents
Criteria, Background, Measurement of effect of dabigatran, Invasive
procedures and Elective surgery

Page 2

Emergency surgery, reversal and overdose

Page 3

Emergency surgery protocol

Appendix 1

Haemorrhage Protocol

Appendix 2

Effect of the new oral anticoagulants on coagulation screens

Appendix 3

Equality impact assessment

Page 7

Criteria
Apixaban, dabigatran and rivaroxaban are new oral anticoagulants that are alternatives to
coumarins (e.g. warfarin) in selected groups of patients for certain indications. This guideline is
for patients receiving apixaban (Eliquis) requiring an invasive procedure, emergency surgery or
treatment for haemorrhage. For patients on rivaroxaban (Xarelto) or dabigatran (Pradaxa)
see alternative guidelines on the intranet .
Background
Apixaban (Eliquis) is a direct factor Xa inhibitor licensed to prevent stroke and systemic
embolism in adult patients with nonvalvular atrial fibrillation. It is used in some patients unable to
take warfarin.
Further information can be found on the APC website www.nottsapc.nhs.uk and the
Nottinghamshire Joint Formulary.
This guideline outlines the steps to be taken in patients who are taking apixaban and require an
invasive procedure or who have bleeding complications.
Measurement of anti-coagulation effect of apixaban
Apixaban does not routinely require monitoring of therapeutic response (unlike warfarin).
However, if a patient has an episode of bleeding or requires an invasive procedure, measurement
of an anticoagulant effect may be advantageous.

A specific anti Xa assay can be used to measure the anticoagulant effect of apixaban,
only after discussion with a haematologist.
N.B. Standard coagulation screening tests cannot assess the degree of anticoagulation for
patients taking apixaban. If a patient is known to be taking apixaban, it should NOT be
assumed that haemostasis is normal even if the coagulation screening tests return normal
results. Bleeding patients, or patients requiring interventional procedures must always be
discussed with a haematologist.
Appendix 3 shows the effect of all the new oral anticoagulants on clotting screens
Invasive procedures and elective surgical interventions
Stop apixaban at least 24 hours before intervention (48 hours if moderate-high risk of bleeding).
The bleeding risk for the procedure needs to be assessed by the clinician performing the
procedure. The relevant bleeding risk vs thrombotic risk (with cessation of anticoagulation) needs
to be assessed and discussed with the patient by the clinician performing the procedure. If
procedure cannot be delayed until at least 24 hours post dose, the increased risk of bleeding
should be assessed against the urgency of the intervention.
2
Apixaban should be re-started post procedure when risk of bleeding is judged to be low.

Emergency surgery see Appendix 1 flowchart below

Reversal or overdose
There is no specific reversal agent and as yet there is no real evidence or experience on the
reversal of apixaban. If the patient has bleeding complications (related to overdose or otherwise) please see Appendix 2 flowchart.
For overdoses contact the UK National Poisons Information Service on 0844 892 0111 and
oncall haematologist via switchboard.

Appendix 1 Patient Receiving Apixaban (Eliquis) Therapy

Emergency Surgery Protocol
STOP Apixaban

Contact Surgeon / Haematologist / Anaesthetist

(If the patient presents within 1 hour of ingestion then consider using activated
charcoal)

Xa assay and additional tests as discussed with haematologists

(Important to make a note of the timing of the last dose of apixaban)

FBC
U&Es

If Xa
RAISED

If Xa
NORMAL

Apixaban effects may be

present

Minimal apixaban effects

present

Maintain BP and Urine output

(Apixaban is around 25% renally
cleared)
Consult with the surgeons to consider
delaying surgery if possible

If surgery can be delayed for

greater than 24 hours:
omit dose of apixaban and
proceed with surgery
following discussion with
surgeon and haematologist

If immediate surgery is required:

consider using IV Octaplex 25 units/Kg
(up to a maximum of 3000 units) or an
alternative prothrombin complex
concentrate. Order via haematology
registrar and obtain from blood bank.
Octaplex administration guidance
available in this guideline

Discuss with surgeons and/or

haematologist post procedure regarding
restarting apixaban

Recheck Xa post administration

and liaise with haematology if
activity still detected

Appendix 2 Patient Receiving Apixaban (Eliquis) Therapy

Haemorrhage Protocol
STOP Apixaban
(If the patient presents within 1 hour of ingestion then consider using activated
charcoal)

Contact Haematologist

Xa assay and additional tests as discussed with haematologists

(Important to make a note of the timing of the last dose of apixaban)

FBC
U&Es

If
Xa RAISED

If Xa NORMAL

Apixaban effects may be

present

Minimal apixaban effects

present. Employ standard
measures

Minor Bleed

Mechanical

compression
Delay next dose of
apixaban or
discontinue

Major Bleed

Life threatening haemorrhage

Maintain BP and Urine

output
(Apixaban is around 25%
renally cleared)
Continues
to bleed

Continues
to bleed

Haemorrhage control measures

Consider tranexamic acid 1g IV

Recheck Xa post Octaplex and

liaise with haematology if activity

still detected.
Discuss with surgeons and/or
haematologist regarding
restarting apixaban

Consider using IV Octaplex 25 units/

Kg (up to a maximum of 3000 units)

on advice of a haematologist (obtain
from blood bank)
Octaplex administration guidance
available in this guideline
5

Appendix 3
Effect of the new oral anticoagulants on coagulation screens
Apixaban, dabigatran and rivaroxaban are new oral anticoagulants that
are alternatives to coumarins (e.g. warfarin) in selected groups of patients for certain indications. All these drugs accumulate in renal impairment. A standard clotting screen has not been validated for assessing
the degree of anticoagulation in a patient taking these agents and
should not be used for this purpose. Consult haematology for advice.

The table below gives information on the drugs effects on coagulation

screens:

Parameter Apixaban
(Eliquis)

Dabigatran
(Pradaxa)

Rivaroxaban
(Xarelto)
Prolonged (in
linear fashion if
neoplastin used as
reagent)
Prolonged
(1.5-1.8 times
control)

PT

Prolonged

No effect

APTT

Prolonged

TT

No effect

Prolonged
(1.4-1.8 times
control) greatly
prolonged if
supratherapeutic
levels
Prolonged

Drug
Activity

Use anti Xa
assay

Platelet
count

No effect

Use Haemoclot
Use anti Xa assay
thrombin inhibitor
assay or ECT
No effect
No effect

D-dimer

Suppressed
levels

Suppressed
levels

Suppressed
levels

Fibrinogen

No effect

Can give falsely

low results

No effect

No effect

Equality Impact Assessment Report

1.

Name of Policy or Service

Response to external best practice policy

2.

Responsible Manager
Owen Bennett (Clinical Quality, Risk and Safety Manager)

3.

Name of person Completing EIA

Julian Holmes

4.

Date EIA Completed

31.5.2013

5.

Description and Aims of Policy/Service

Guideline for patients receiving Apixaban (Eliquis) requiring Emergency Surgery or
treatment for Haemorrhage

6.

Brief Summary of Research and Relevant Data

NICE guideline, BCSH guideline, SPC for apixaban

7.

Methods and Outcome of Consultation

N/A

8.

Results of Initial Screening or Full Equality Impact Assessment:

9.

Equality Group

Assessment of Impact

Age

No Impact Identified

Gender

No Impact Identified

Race

No Impact Identified

Sexual Orientation

No Impact Identified

Religion or belief

Some Jehovah witnesses may not

accept Octaplex

Disability

No Impact Identified

Dignity and Human Rights

No Impact Identified

Working Patterns

No Impact Identified

Social Deprivation

No Impact Identified

Decisions and/or Recommendations (including supporting rationale)

From the information contained in the procedure, and following the initial screening, it is my
decision that a full assessment is not required at the present time.

10. Equality Action Plan (if required)

N/A
11. Monitoring and Review Arrangements
Review November 2015
7