The Queen Elizabeth Hospital King’s Lynn NHS Foundation

The Queen Elizabeth Hospital King’s Lynn NHS Foundation Trust Clinical Guideline for the Management of Over Anticoagulation and Bleeding on Antithrombotic

Drugs in Adults

Clinical Guideline Author: Dr M D Lewis Authors title: Consultant Haematologist Approved by: Hospital Thrombosis Committee Date approved: April 2020 Review date: April 2023 Page 1 of 20

A Clinical Guideline For use in:

Organisation-wide

By: All medical and nursing staff

For: For all adult patients on antithrombotic drugs that have

been over anticoagulated or are bleeding.

Division responsible for document:

Core services including Outpatient services

Key words:

Antithrombotic drugs, warfarin, dabigatran,

rivaroxaban, apixaban, edoxaban, aspirin, clopidogrel, bleeding, overanticoagulation, Beriplex, FFP,

Idarucizumab.

Name of document author: Dr M D Lewis

Job title of document author: Consultant Haematologist

Name of document author’s Line Manager: Hugh Warren

Job title of author’s Line Manager: Divisional Director

Supported by: Sr E Macleod-Collins, Anticoagulation Advanced Nurse Practitioner

Pat Fysh, Coagulation Co-ordinator

Assessed and approved by the:

Hospital Thrombosis Committee / Clinical Governance Meeting Drugs and Therapeutics Committee If approved by committee or Governance Lead Chair’s Action; tick here

Date of approval: April 2020

Ratified by or reported as approved to: Clinical Guidelines Committee

Final Approval By and Date: Dr H Altemimi 29/06/2020

To be reviewed before:

This document remains current after

this date but will be under review April 2023

To be reviewed by: Dr M D Lewis, Consultant Haematologist

Reference: A0.8

Version No: v3

Description of changes: Put into new Trust format and updated with antidote

information of dabigatran etexilate (Pradaxa)

Compliance links: NICE

If Yes - does the guidance deviate from the recommendations of NICE? If so why?

No

This guideline has been approved by the Trust's Clinical Guidelines Group as an aid to the diagnosis and management of relevant patients and clinical circumstances. Not every patient or situation fits neatly into a standard guideline scenario and the guideline must be interpreted and applied in practice in the light of prevailing clinical circumstances, the diagnostic and treatment options available and the professional judgement, knowledge and expertise of relevant clinicians. It is advised that the rationale for any departure from relevant guidance should be documented in the patient's case notes. The Trust's guidelines are made publicly available as part of the collective endeavour to continuously improve the quality of healthcare through sharing medical experience and knowledge. The Trust accepts no responsibility for any misunderstanding or misapplication of this document.


Drugs in Adults


1. Contents page Page

2 Definitions of terms used 4

3 Quick reference 5

4 Objective 6

5 Rationale 6

6 Processes to be followed: 6

General measures to stop bleeding in all patients taking antithrombotic drugs 6

Non-pharmacological measures 6

General haemostatic agents 7

Management of over anticoagulation on warfarin 8

Management of major or life threatening bleeding on warfarin 9

Beriplex 10

Important dosing advice 11

Management of significant bleeding without haemodynamic compromise 11

Active non-life threatening bleeding requiring rapid reversal of warfarin 11

Minor bleeding 12

High INR (>4.0) with no bleeding 12

Reversal of low molecular weight heparin or unfractionated heparin 13

Direct oral anticoagulants (DOACs) 14

Dabigatran 14

Reversal of Dabigatran with Idarucizumab (praxbind) 15

Restarting antithrombotic therapy 15

Direct oral factor Xa inhibitor – rivaroxaban (Xarelto), apixaban (Eliquis) and

edoxaban (Lixiana)

16

Bleeding on aspirin or clopidogrel 17

Other drugs 17

7 Summary of development and consultation process undertaken 18

8 References 18

9 Equality impact assessment 19

10 Monitoring compliance 21


Drugs in Adults


2. Definitions of Terms Used

Antithrombotic/Anticoagulant drugs:

Vitamin K Antagonist (VKA) – Warfarin, Acenocoumarol (Sinthrome)

Direct thrombin inhibitor – Dabigatran (Pradaxa)

Direct Factor Xa inhibitor – Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Lixiana)

Low Molecular Weight Heparin (LMWH) – Enoxaparin, Dalteparin, Tinzaparin

Unfractionated Heparin (UFH)

Reversal agents:

Prothrombin Complex Concentrate (PCC) - Beriplex

FFP – fresh frozen plasma

Protamine Sulphate

Praxbind (Idarucizumab).


Drugs in Adults


3. Quick reference

▪ General Measures to Stop Bleeding – page 6

▪ Management of major or life threatening bleeding on warfarin - page 9

▪ Management of significant bleeding without haemodynamic compromise - page 11

▪ Reversal of LMWH or UFH - page 13

▪ Reversal of DOACs – page 14-16

▪ Bleeding on aspirin or clopidogrel - page 17

▪ Other drugs –page 17

For full information / further details: please see rest of document.


Drugs in Adults


4. Objective

To provide management advice for adult patients experiencing bleeding symptoms or over-

anticoagulation while taking antithrombotic drugs. 5. Rationale

To provide management advice for adult patients on antithrombotic drugs who have been over-

anticoagulated or have bleeding using evidence based recommendations. It includes general

measures to stop bleeding and information for rapid reversal of Warfarin, and Dabigatran where a

specific antidote exists, plus guidance for the other Direct Oral AntiCoagulants (DOACs) and LMWH.

Oral vitamin K will take approximately 24 hours to counteract the effect of warfarin.

IV Vitamin K will take approximately 6-8 hours to counteract the effect of warfarin.

Beriplex will begin to work immediately.

Idarucizumab (Praxbind) will begin to work immediately. 6. Processes to be followed

• Establish indication for anticoagulation (with dates of events)

• Establish when the last dose of antithrombotic drug was taken and how much.

• Check renal function, LFT, FBC, PT, APTT, INR (for warfarin ONLY), APTTR (for UFH ONLY)

• General measures. General Measures to Stop Bleeding in All Patients Taking Antithrombotic Drugs

For all patients, it is important to balance bleeding risk and thrombotic risk. To do this, you must

document the indication for anticoagulation (including dates of VTE, stroke), antithrombotic used

(including target INR if warfarin), drug dose and timing of last dose. If anticoagulation is to be

reversed, thrombotic risk factors should be acknowledged.

Non-pharmacological measures

In many cases, simple non-pharmacological measures and stabilisation of the patient whilst the

antithrombotic is eliminated are sufficient to treat or prevent bleeding (see table below).

The Queen Elizabeth Hospital King’s Lynn NHS Foundation Trust Clinical Guideline for the Management of Over Anticoagulation and Bleeding on

Antithrombotic Drugs in Adults


General non-pharmacological measures

1. Stop the antithrombotic drug

2. Document the timing and dose of the last drug dose and presence of pre-existing renal or

hepatic impairment

3. Estimate the half-life and length of functional defect induced by the drug

4. Assess the source of the bleeding

5. Request full blood count, prothrombin time, activated partial thromboplastin time,

thrombin time, fibrinogen concentration, serum creatinine levels

6. If available, request a specific laboratory test to measure the antithrombotic effect of the

drug (warfarin – INR, LMWH – Anti-Xa, UFH – APTTR or Anti-Xa)

7. Correct haemodynamic compromise with intravenous fluids and red cell transfusion

8. Apply mechanical pressure, if possible

9. Use endoscopic, radiological or surgical measures

General haemostatic agents

Specific antidotes are not always available to reverse antithrombotic drugs in emergencies.

However, general prohaemostatic agents, such as Tranexamic acid, may be useful in some

circumstances. Recombinant activated factor VII (rFVIIa, Novoseven®), prothrombin

complex concentrates (PCC) and activated PCC [APCC; e.g. factor VIII inhibitor bypass

activity (FEIBA)] are often considered as agents for reversal of the effect of antithrombotic

drugs. However, off-label use of rFVIIa for critical bleeding was associated with arterial

thrombosis in 5.5% vs. 3.2% in placebo in all patient groups and 10.8% vs. 4.1% in placebo

in patients >75 years. Reversal of the effect of an antithrombotic is an unlicensed

indication for rFVIIa but this agent is often considered as a last resort when all other

measures have failed and the risks and benefits are carefully documented.

If the patient is likely to have therapeutic levels of anticoagulation in circulation, reversal

should be considered for major/life threatening bleeding or when emergency surgery is

required.

Drug Half-life

Dabigatran 12-14 hours if CrCl ≥80

~15 hours if CrCl ≥50 - <80

~18 hours if CrCl ≥30 - <50

~27 hours if CrCl <30

Rivaroxaban 5-9 hours in young patients

11-13 hours in elderly patients

Apixaban 12 hours

Edoxaban 10-14 hours

Low molecular weight

heparin

4-7 hours

Warfarin 40 hours




NB: FFP (FRESH FROZEN PLASMA) SHOULD NEVER BE USED FOR THE REVERSAL OF

WARFARIN (WHEN PCC IS AVAILABLE IE BERIPLEX). MANAGEMENT OF OVER-ANTICOAGULATION ON WARFARIN

A precipitating factor must be identified as a cause of the over-anticoagulation.

eg infection, new medication, liver dysfunction) so that the warfarin be dosed accordingly

in the future.

INR Presence of bleeding Action required

INR 5.0 - 8.0 No bleeding 1) Stop warfarin

2) Restart a lower dose

when INR <5.0

INR 5.0-8.0 Minor bleeding or risk factors

for bleeding

1) Stop warfarin

2) Give vitamin K 1mg

orally

3) Restart at a reduced

dose when INR<5.0

INR >8.0

ALL patients with an INR

greater than 8.0 require

reversal

No bleeding or minor bleeding 1) Stop warfarin

2) Give phytomenadione

(vitamin K1)1-5mg orally

using the IV preparation

(Konakion® MM) or

Menadiol 10mg tablets

to be SUCKED and NOT

to be swallowed, for

partial reversal. Higher

doses are required for

full reversal.

3) Restart warfarin at a

lower dose when INR

<5.0 if no risk factors for

bleeding




NB: FFP should NOT be used for the reversal of warfarin.




Other risk factors for bleeding:

Age >70 years

Previous bleeding complications

Uncontrolled Hypertension

Diabetes

Renal/Liver failure

Concurrent use of anti-platelet agents

Unexpected bleeding at therapeutic levels – Always investigate the possibility of

underlying cause (e.g. unsuspected renal or GI tract pathology)

MANAGEMENT OF MAJOR OR LIFE-THREATENING BLEEDING ON WARFARIN

Definition of life-threatening bleeding – examples include:

Intracranial or rapid onset neurological signs

Significant head injury

Intra-ocular (not conjunctival) bleeds

Compartment syndrome

Pericardial bleed

Active bleeding with shock

Send blood for urgent clotting assessment

FBC, INR

Prothrombin time, APTT, Fibrinogen

Baseline renal and liver function

Group and Save with X match (remember may need a 2nd sample if first time

patient)

Contact the consultant haematologist on-call if required at this stage

Oral vitamin K will take approximately 24 hours to counteract the effect of

warfarin.



Stop warfarin and reverse anticoagulation

1) Give vitamin K1 5-10 mg IV slowly (over 10-15 minutes) – can cause

anaphylaxis if given too quickly

**In patients admitted with a fractured neck of femur (NOF) who will

require surgery, 10mg iv has been shown to be more effective than 5mg

(source: local audit).**

2) Give Prothrombin Complex Concentrate – BERIPLEX – dose according to INR

– See table below

a. Kept in pharmacy night store




b. Fast onset of action <10 mins

c. Reconstitute according to instructions in pack and give over 15 – 20

minutes (For patients <70kg maximum 0.12ml/kg/min, top maximum

rate is 8.0 ml/min)

d. Has half-life of ONLY 6 hours – essential to give vitamin K at the same

time

3) Recheck INR - 20 minutes and 6 hours post infusion of Beriplex

4) Seek further advice if no improvement in INR

5) The degree of reversal must be decided on an individual basis. All patients

with bleeding should be evaluated to identify if there is a local anatomical

reason for bleeding, which must also be addressed.

** TRANSFUSION TRANSMITTED INFECTION: Both FFP and Beriplex are plasma products THEY CARRY THE RISK OF TRANSFUSION TRANSMITTED INFECTION AND OTHER

TRANSFUSION RELATED COMPLICATIONS. IT IS IMPORTANT THAT THEY ARE USED

APPROPRIATELY AND THEIR PRESCRIPTION AND RATIONALE FOR USE ARE RECORDED IN

THE PATIENT’S NOTES

BERIPLEX

Indications ►Treatment and perioperative prophylaxis of bleeding in acquired deficiency of the prothrombic complex coagulation when rapid correction of the deficiency is required. ►Serious bleeding secondary to Vitamin K antagonists ►Reversal of warfarin when emergency surgery is required within 6 hours

Contraindications ►Known hypersensitivity ►Risk of thrombosis, angina, recent AMI (exception: life threatening haemorrhage secondary to warfarin over dosage & before induction of fibrinolytic therapy ►Caution severe liver failure ►DIC – Beriplex maybe used after termination of the consumptive state ►History of heparin-induced thrombocytopenia

Side-effects ►Allergy or anaphylactic type reactions – discontinue Beriplex immediately ►Fever ►Antibody development to one or more clotting factors ►Heparin induced thrombocytopenia ►Risk of thromboembolic episodes

Please note: ► The action of warfarin may last longer than the action of Beriplex ► Check INR at 20 minutes and 6 hours post infusion ► Use clinical judgement on a case-by-case basis to decide if the potential benefit of treatment with Beriplex outweighs the potential thrombotic complications in certain patients

Patient’s INR Recommended dose of Beriplex Maximum dose (cap at 100kg body weight (see next page)

2.0 – 3.9 25 units/ kg body weight 2,500 unit

4.0 – 6.0 35 units/ kg body weight 3,500 units

> 6.0 50 units/ kg body weight 5,000 units

** The single dose should not exceed 5,000 IU (200ml of Beriplex). Vial sizes = 250 IU, 500 IU) **




IMPORTANT DOSING ADVICE

1. For the purposes of dose calculation, patients should have their weight

capped at 100kg. For example, if a patient weighs 130kg, with an INR of 5.0,

they should still only receive 3500iu of Beriplex (NOT 4550iu).

2. The maximum single dose is 5,000iu Beriplex, which must not be exceeded.

Taken with point 1, if a patient had an INR of greater than 6, and weighed

100kg or above, they would still receive the same maximum dose of 5,000iu.

If there is any question about the interpretation of dosing guidance, the case should be

discussed with the Haematologist on-call.

MANAGEMENT OF SIGNIFICANT BLEEDING WITHOUT HAEMODYNAMIC COMPROMISE

Active non-life threatening bleeding – requiring rapid reversal of warfarin




Ascertain the following information: -

1) The indication for anticoagulation, noting dates of any previous thromboembolic

events.

2) The target INR range.

3) The usual dose of warfarin therapy.

4) From this ascertain the thrombotic risk of reversing anticoagulation - high or low. DISCUSS WITH A HAEMATOLOGIST IF IN ANY DOUBT.

Establish INR

Withhold warfarin

Give vitamin K 5-10 mg by slow intravenous injection

Consider using Beriplex

Recheck clotting screen at 4 hours or sooner if there is clinical deterioration

Repeat if necessary and seek haematological advice

Bleeding may occur with INR in the therapeutic range. In these circumstances it may be

still necessary to reverse anticoagulation to allow treatment of bleeding.




Minor bleeding (eg epistaxis or haematuria)

Establish INR

Withhold warfarin

If no other risk factors for haemorrhage, withhold warfarin until INR <5.0

If risk factors for haemorrhage or minor bleeding (e.g. age >70 years,

previous bleeding complications, epistaxis), consider giving Vitamin K1 2mg

oral or 1mg by slow IV injection (i.e. to bring the INR down faster)

Recheck clotting screen at 24 hours or sooner if clinical deterioration

Restart warfarin once bleeding risk has subsided

High INR (>4.0) with no bleeding

If INR > 4.0 withhold warfarin for 1 day then continue with lower dose.

If INR >5.0 withhold warfarin for 2 days. Re-check INR to ensure it has fallen,

If <3.5 restart warfarin at lower dose.

If INR >6.0 withhold warfarin for 3 days. Re-check INR to ensure it has fallen,

If <3.5 restart warfarin at lower dose.

If INR >8.0 give 1-5mg vitamin K1 orally (using the IV preparation) or

menadiol 10mg tablet SUCKED - DO NOT SWALLOW WHOLE for partial

reversal. Recheck INR 12-18 hours post dose. Restart warfarin at reduced

dose.

IMPORTANT - Ascertain any possible reason for INR elevation (e.g. antibiotic

therapy, illness, alcohol, medication change etc.)

• If cause established, which has now passed restart warfarin at usual

dose.

• If reason persists, restart warfarin at lower dose (reduce by

approximately 10%)

• If INR elevation is due to heart failure, major medical illness or increase

in liver enzymes, seek advice before restarting warfarin.




REVERSAL OF LMWH OR UNFRACTIONATED HEPARIN

ESTABLISH LAST DOSE AND HALF-LIFE OF ANTITHROMBOTIC DRUG

NB Half life of IV UFH is 60-90 minutes; Half life of enoxaparin is approx. 7 hours

(Other LMWH may vary)

The anticoagulant effects of enoxaparin can be largely neutralised by the slow intravenous injection of Protamine, but even with high doses of Protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralised (maximum about 60%). ** Decisions regarding the necessity and dose of subsequent Protamine injections should be based on clinical response rather than measurement of anti Xa results. The physician should also consider that the amount of enoxaparin in the body drops to 50% after 8 hours and 33% or less after 12 hours

FULL REVERSAL OF UNFRACTIONATED HEPARIN WITH PROTAMINE

1mg of Protamine will neutralise 100 units of unfractionated heparin

(NB: maximum single dose of Protamine 50mg)

PARTIAL REVERSAL OF LMWH (eg enoxaprin) WITH PROTAMINE

Time since last dose of enoxaparin -

< 8 hours: 1mg Protamine per 1mg of enoxaparin (Max dose 50mg)

8 – 12 hrs: 0.5mg Protamine per 1mg of enoxaparin (Max dose 50mg)

> 12 hrs: May not be required

ADMINISTRATION OF PROTAMINE

Administer as slow IV push over 10 minutes

Do not give more than 50mg of Protamine in a single dose

Rapid administration can cause hypotension and anaphylactoid

reactions

Onset of action, neutralisation of UFH ~ 5 minutes

Excessive doses (>100mg) can cause paradoxical anticoagulation

For full details see Product information




DIRECT ORAL ANTICOAGULANTS (DOACS)

IMPORTANT: the PT, APTT, INR and APTTR CANNOT BE USED to quantify the anticoagulant effect of DOACs. (limited interpretation may be possible in certain circumstances - and should be discussed with a Haematologist) Dabigatran (Pradaxa) a Direct oral thrombin inhibitor

Rationale

Following oral administration, plasma levels peak within 2–3 h. In individuals with normal

renal function, the half-life is 13 h. Dabigatran etexilate is 80% eliminated by the kidneys

and has a prolonged plasma half-life in patients with renal impairment (plasma half-life

22–35 h with creatinine clearance < 30 ml/min). In the RE-LY trial of dabigatran etexilate in

atrial fibrillation the annual risk of major bleeding was 2.71% and 3.11% with the 110 and

150 mg dabigatran etexilate doses, respectively, in comparison to 3.36% for patients

treated with warfarin. It must be appreciated, however, that both these figures are

conservative as this pivotal trial excluded many real-life situations of patients with

extreme body weights, significant renal impairment or multiple co-morbidities.

A normal thrombin time and a normal APTT suggest that a high level of dabigatran

etexilate is unlikely. A degree of anticoagulation cannot be excluded but the intensity

might be regarded as no more than that achieved with a prophylactic dose of low

molecular weight heparin.

Reversal

• Establish indication for anticoagulation.

• Establish when last dose was taken and how much.

• Check renal function.

• General measures.

Oral activated charcoal – in bleeding patients who have taken a dose of dabigatran

etexilate in the last 2 hours, this should be considered to prevent further absorption.

Minor bleeding – In view of the relatively short dabigatran half-life, this should be

managed by withholding further doses of the drug and using standard measure, such as

direct pressure, simple surgical intervention and fluid replacement.




Reversal of Dabigatran (Pradaxa) with IDARUCIZUMAB (Praxbind)

Praxbind (Idarucizumab) is a specific reversal agent for Pradaxa (dabigatran etexilate) and

is indicated in adults (there is not data for its use in the paediatric population) when rapid

reversal of its anticoagulant effects is required, i.e.:

For emergency surgery/urgent procedures

In life-threatening or uncontrolled bleeding.

1. The recommended dose of Praxbind (Idarucizumab) is 5 g (2x2.5 g/50 mL vials), given

intravenously as two consecutive infusions over 5 to 10 minutes each or as a bolus

injection.

No dose adjustments are required for renal/hepatic impairment.

In a subset of patients, recurrence of plasma concentrations of unbound dabigatran

etexilate and concomitant prolongation of clotting tests have occurred up to 24 hours

after administration of Praxbind (idarucizumab).

2. Administration of a second 5 g dose of Praxbind (idarucizumab) may be considered in

the following situations:

• recurrence of clinically relevant bleeding together with prolonged clotting times, or

• if potential re-bleeding would be life-threatening and prolonged clotting times are

observed, or

• patients require a second emergency surgery/urgent procedure and have prolonged

clotting times.

Haemodialysis, haemofiltration and charcoal haemoperfusion offer the possibility of

enhanced clearance of the active drug. However, while this may be of benefit in theory,

the difficulties of inserting a dialysis line in an unwell, anticoagulated patient, plus the

length of time required for the dialysis procedure, mean that this technique is expected to

be used very rarely. Restarting Antithrombotic Therapy

Dabigatran treatment can be re-initiated 24 hours after administration of Praxbind,

if the patient is clinically stable and the bleeding risk has passed. Other

antithrombotic therapy (e.g. low-molecular weight heparin) can be started at any

time, once safe to do so.




Direct oral Xa inhibitors - Rivaroxaban (Xarelto), Apixaban (Eliquis) and Edoxaban (Lixiana)

Rationale

Following an oral dose, rivaroxaban, apixaban and Edoxaban reach a peak at 3 h and have

half-lives of 7–9, 9–14 and 10-14h respectively, in patients with normal renal function. The

Xa inhibitors are mostly metabolized by the liver with small amounts excreted unchanged

by the kidneys. In the ROCKET AF trial, the annual risk of major bleeding was 3.6% for 20

mg once daily rivaroxaban and 3.4% for warfarin. In the ARISTOTLE trial, which compared

apixaban 5 mg twice daily with warfarin in AF, the annual risks of major bleeding were

2.13% and 3.09%, respectively. As these clinical trials restricted recruitment of some

patient groups, such as at the extreme of body weight, significant renal impairment and

multiple comorbidities, the real risk of bleeding experienced in clinical practice is likely to

be higher.

A normal PT suggests against a therapeutic intensity of anticoagulation being

present from rivaroxaban therapy. Although some degree of anticoagulation

cannot be excluded by a normal PT, the intensity could be regarded as no more

than that achieved with a prophylactic dose of low molecular weight heparin. The PT has no role at all in assessing the anticoagulant effects of Apixaban and Edoxaban

No antidote is currently available at QEHKL for use in patients with major or life-

threatening bleeding.

There are no published clinical trials or other high quality evidence addressing the

management of bleeding on rivaroxaban or apixaban.

Other specific antidotes such as a recombinant Xa-analogue are still being

investigated in clinical trials.

Reversal

• Establish indication for anticoagulation.

• Establish when last dose was taken and how much.

• Check renal function.

• General measures.

For minor bleeding - in view of the short half-life, supportive measures, such as

direct pressure, minor surgical intervention and fluid replacement, should be tried.

Life-threatening bleeding - PCC (i.e. Beriplex 50u/kg) and rFVIIa 90mcg/kg should be

considered following discussion with the on call Haematologist.




As these drugs show high plasma protein binding they would not be expected to be

dialysable. BLEEDING ON ASPIRIN OR CLOPIDOGREL.

Consider platelet transfusion (one unit) early in bleeding patient.

Discuss with Haematologist on call.

OTHER DRUGS

Danaparoid sodium

Danaparoid is a heparinoid used mainly in the treatment of Heparin Induced

Thrombocytopenia (HIT), consisting of a mixture of glycosaminoglycans with an anti-

Xa/anti-IIa ratio > 20. Danaparoid is excreted renally and has a plasma half-life of anti-Xa

activity of approximately 24 h. Danaparoid may be monitored by anti-Xa assay using a

danaparoid standard (must notify lab). Major bleeding occurred in 8.1% of patients

treated with danaparoid for HIT. An ex vivo study showed partial restoration of thrombin

generation when rFVIIa was added at supra-therapeutic doses to plasma spiked with

danaparoid, but not with addition of APCC and FFP.

There is no specific antidote for danaparoid. Management of bleeding should be

through cessation of treatment and general haemostatic measures

Plasmapheresis removes danaparoid effectively from the circulation and may be

considered for critical bleeding. Fondaparinux

Fondaparinux is a synthetic pentasaccharide with indirect anti-Xa activity that achieves

steady state antithrombotic activity after 3–4 d of use. The plasma half-life is significantly

longer than LMWH at 17–20 h (with normal renal function) and up to 72 h (when

creatinine clearance is <30 ml/min).

There is no specific antidote for fondaparinux. Management of bleeding should be

through cessation of treatment and general haemostatic measures.

Recombinant FVIIa 90mcg/kg may partially correct the haemostatic defect from

Fondaparinux, and should be considered for critical bleeding, but only after

discussion with a Consultant Haematologist, and only once other measures have

failed.




8. Summary of development and consultation process undertaken before registration and dissemination

The authors listed above drafted this document on behalf of the Hospital Thrombosis Committee who has agreed the final content. During its development it has been

circulated for comment to: Hospital Thrombosis Committee and Drugs and Therapeutics committee.

This version has been endorsed by the Hospital Thrombosis Committee. 9. References

BRITISH COMMITTEE FOR STANDARDS IN HAEMATOLOGY (BCSH) (2012). Guideline on the

management of bleeding in patients on antithrombotic agents. 4th Edition.

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE (nice) 2016. Reversal of the

anticoagulant effect of dabigatran: Idarucizumab

BOEHRINGER INGELHEIM (2015). Praxbind 2.5g/50ml solution for injection/infusion,

summary of product characteristics (online, January 2017)

http://www.acepnow.com/article/options-approaches-outpatient-treatment-deep-vein-

thrombosis-emergency-physicians/?singlepage=1&theme=print-friendly




EQUALITY IMPACT ASSESSMENT

STAGE 1 - SCREENING

Name & Job Title of Assessor:

Dr M D Lewis, Consultant Haematologist

Date of Initial Screening: April 2020

Date of Review: April 2023

Policy or Function to be assessed:

Yes/No

Comments

1. Does the policy, function, service or project affect one group more or less favourably than another on the basis of:

Race & Ethnic background No

Gender including transgender No

Disability:- This will include consideration

in terms of impact to persons with

learning disabilities, autism or on

individuals who may have a cognitive

impairment or lack capacity to make

decisions about their care

No

Religion or belief No

Sexual orientation No

Age Yes Applies to adult patients only.

Patients under the age of 18 are to

be seen by a Paediatrician

2. Does the public have a perception/concern regarding the potential for discrimination?

No

If the answer to any of the questions above is yes, please complete a full Stage 2 Equality Impact Assessment.

Signature of Assessor: Dr M D Lewis Date: April 2020

Signature of Line Manager: Hugh Warren Date: April 2020




STAGE 2 – EQUALITY IMPACT ASSESSMENT

If you have indicated that there is a negative impact on any group in part one please complete the following, is that impact:

Yes/No Comments

1. Legal/Lawful under current equality legislation?

N/A

2. Can the negative impact be avoided? No Not desirable.

Clinically appropriate.

3. Are there alternatives to achieving the policy/guidance without the impact?

N/A

4. Have you consulted with relevant stakeholders of potentially affected groups?

No

5. Is action required to address the issues? No

It is essential that this Assessment is discussed by your management team and remains

readily available for inspection. A copy including completed action plan, if appropriate,

should also be forwarded to the Equality & Diversity Lead, c/o Human Resources

Department.




MONITORING COMPLIANCE

Key elements Process for Monitoring

By Whom (Individual / group /committee)

Responsible Governance Committee /Dept

Frequency of monitoring

Documents

The Queen Elizabeth Hospital King’s Lynn NHS Foundation