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

Contact Name and Job Title (author) 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)

November 2015

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

Adult patients receiving apixaban requiring emergency surgery or treatment of haemorrhage

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?

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

2b at least one other type of well-designed quasi-experimental study

3 well designed non-experimental descriptive studies (ie comparative / correlation and case studies)

4 expert committee reports or opinions and / or clinical experiences of respected authorities

5 recommended best practise based on the clinical experience of the guideline developer

1b, 4

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.

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Protocol for patients receiving Apixaban (Eliquis) requiring an invasive procedure, emergency surgery or treatment for haemorrhage

Contents

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. Apixaban should be re-started post procedure when risk of bleeding is judged to be low.

Criteria, Background, Measurement of effect of dabigatran, Invasive procedures and Elective surgery

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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

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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 other-wise) please see Appendix 2 flowchart.

For overdoses contact the UK National Poisons Information Service on 0844 892 0111 and oncall haematologist via switchboard.

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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 NORMAL

If Xa RAISED

Minimal apixaban effects present

Apixaban effects may be 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

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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 NORMAL If Xa RAISED

Minimal apixaban effects present. Employ standard

measures

Apixaban effects may be present

Maintain BP and Urine output

(Apixaban is around 25% renally cleared)

Minor Bleed

Mechanical compression

Delay next dose of apixaban or discontinue

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

Haemorrhage control measures Consider tranexamic acid 1g IV

Major Bleed Life threatening haemorrhage

Continues to bleed

Continues to bleed

Recheck Xa post Octaplex and liaise with haematology if activity still detected.

Discuss with surgeons and/or haematologist regarding restarting apixaban

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Apixaban, dabigatran and rivaroxaban are new oral anticoagulants that are alternatives to coumarins (e.g. warfarin) in selected groups of pa-tients for certain indications. All these drugs accumulate in renal impair-ment. 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:

Appendix 3 Effect of the new oral anticoagulants on coagulation screens

Parameter Apixaban (Eliquis)

Dabigatran (Pradaxa)

Rivaroxaban (Xarelto)

PT Prolonged No effect Prolonged (in linear fashion if neoplastin used as reagent)

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

Prolonged (1.5-1.8 times control)

TT No effect Prolonged No effect

Drug Activity

Use anti Xa assay

Use Haemoclot thrombin inhibitor assay or ECT

Use anti Xa assay

Platelet count

No effect No effect No effect

D-dimer Suppressed levels

Suppressed levels

Suppressed levels

Fibrinogen No effect Can give falsely low results

No effect

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

6. Brief Summary of Research and Relevant DataNICE 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. 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 ArrangementsReview November 2015

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

ContentsCriteriaBackgroundMeasurement of anti-coagulation effect of apixabanInvasive procedures and elective surgical interventionsEmergency surgeryReversal or overdoseAppendix 1Appendix 2Appendix 3Equality Impact Assessment Report