Oral and parenteral anti-coagulation for inpatients at COCH 2014

ORAL AND PARENTERAL ANTI-COAGULATION FOR INPATIENTS

Introduction

Purpose

Duties and responsibilities

Qualifications

Benefits vs the risks of anticoagulant therapy for individual patients

How to use Intravenous Heparin (for Full Therapeutic Anticoagulation)

Prophyaxis with low molecular weight heparin

Treatment with low molecular weight heparin

Renal Function

Tinzaparin Dosage Schedule

Risks and warnings for treatment with tinzaparin

Monitoring

Protamine

New Oral Anticoagulants (NOACs)

Prescribing warfarin.

Starting warfarin

Suggested guidance on dose adjustment for maintenance treatment for inpatients

Stopping warfarin therapy.

Discharge of Patients on Anticoagulation

Transfer of care

Pharmacists’ responsibilities for discharge prescriptions.

Acknowledgments

Glossary of terms

Sources / References

Introduction

This guideline has been developed in a response to the NPSA Alert “Patient safety alert 18. Actions that can make anticoagulant therapy safer”.

Purpose

The purpose of this guideline is to promote the safe use of anticoagulation in in-patients at the Countess of Chester NHS Foundation Trust, and to provide nursing, medical and pharmacy staff with supporting information. In the event that these guidelines are not followed, patients are at risk from potentially serious adverse events.

Duties and responsibilities

It is the responsibility of all staff involved in the anticoagulation of patients at COCH, to take note of the content of these guidelines, and to seek support where they are unsure of the appropriate course of action.

Healthcare professionals must check that doses are appropriate before prescribing, administering or dispensing warfarin, heparin and low molecular weight heparin.

Qualifications

These guidelines are intended for use by medical staff of grade F1 and above, registered nurses and registered pharmacists working within their own level of competence and training.

Competency and training

All new prescribers working at COCH must attend the core induction medicines management section which includes a brief session on anti-coagulant prescribing.

New F1 doctors, must attend the induction training which includes a session on anti-coagulation and prior to this, they must have completed the BMJ e-learning modules listed below. They should bring their certificates of completion with them to induction, and have this recorded on the Electronic Staff Record. All clinical pharmacists should also complete these modules on induction and periodically thereafter:

Starting patients on anticoagulants: how to do it:

Maintaining patients on anticoagulants: how to do it:

NB: There is an additional module “How to reverse the effects of warfarin in hospital practice: an update” which should be completed at an appropriate point during junior doctor training.

All F1 doctors must attend an anti coagulant update during their 2nd 6 months

It is good practice for senior staff to ensure that anticoagulation prescription charts are reviewed during ward rounds to monitor prescribing by junior staff.

Junior staff must alert senior member of their team if a patients INR is significantly out of range for more than 2 days or, if the INR is significantly raised. Advice may be obtained from the ward pharmacist or from the anticoagulation team.

Benefits vs the risks of anticoagulant therapy for individual patients

Prior to prescribing anticoagulation a risk benefits analysis should be made for each patient by the responsible clinician. Consideration should be given to contraindications to anticoagulation, including haemophilia, bleeding disorders, severe thrombocytopenia, peptic ulcer, recent cerebral haemorrhage, severe hypertension or liver disease, and after major trauma. Warfarin should not be prescribed to women in the first trimester in pregnancy. Renal failure should also be a consideration for patients on heparin and NOACs. The ability of the patient to comply with warfarin therapy and an assessment of their risk of falls should also be assessed.

How to use Intravenous Heparin (for Full Therapeutic Anticoagulation)

Local consensus agreement:Low molecular weight heparin (LMWH: tinzaparin or enoxaparin) is the preferred heparin product in most clinical situations. If unfractionated heparin is required, consider a switch to LMWH at the earliest opportunity.

NB: Where infusions of Heparin Sodium (unfractionated) are used, a standard, ready-to-use presentation of 1000 units in 1ml is used. Changes in daily dose should be made by adjusting the rate of administration.

  1. Decide whether a loading dose for immediate anticoagulation is required, or whether more gradual anticoagulation is acceptable, in which case, a loading dose is not required.
  2. A baseline INR, APTT ratio, platelet count should be done prior to starting the heparin infusion.

3. Choose a loading dose appropriate for the patients condition. As a general rule, a standard or usual dose would be 5000 units of heparin by intravenous bolus.This may alter dependent upon individual patient & clinical factors. See the Pulmonary Embolism thrombosis guidelines for the dose post Tenectaplase administration. Use 5000units in 5ml heparin to deliver the required loading dose.

4. Establish an infusion of heparin; the amount depends on the clinical situation.

5. Approx. 40000 units/24 hrs is needed for full anticoagulation in a 70 kg adult, so proceed as follows:

i. Draw up 40 000units in 40ml heparin into a 50ml luer-lock syringe

ii. Start at 1.3ml/hr using an appropriately sized syringe pump. If the patient has additional bleeding risks or renal impairment consider reducing this initial rate to 1ml/hr

6. Check APTT 6 – 8 hours after starting infusion (use discretion out of hours)

7. Change the infusion rate to achieve the APTT range of 2.0 – 3.0 as set out below:

  1. Less Heparin is required peri and post operatively, or after fibrinolytic therapy, or depending on the case, and adjustments to this guidance must be made.
  2. In these cases, a useful guide is to start at 1000 units/hr (i.e. 1 ml per hour – 24000 units per day) and adjust upwards if necessary.
  3. Note that IV heparin by infusion may need to be stopped peri-operatively.
  4. See separate guidance on management of peri-operative patients.

APTT Monitoring and dose alterations.

The APTT ratio is the key indicator in determining the response to heparin therapy. The advice given against each APTT range should be interpreted in tandem with an assessment of the patient’s clinical condition and their ‘bleeding’ status in particular.

APTT Ratio / Approx. seconds / Change
4.9 or above / 141 or above / Over anti-coagulated patient. Stop the infusion for at least one hour and reassess the APTT ratio. Reduce rate by 0.5ml/hour when restarting after checking there is no bleeding.
4.0 – 4.8 / 111 - 140 / Reduce rate by 0.3ml/hour.
3.1 – 3.9 / 89 - 110 / Reduce rate by 0.1ml/hour.
2.0 – 3.0 / 58 - 88 / No change.
1.3 – 1.9 / 38 - 57 / Increase rate by 0.2ml/hour.
< 1.3 / <38 / Increase rate by 0.4ml/hour.
  • Repeat APTT approximately every 6-8 hours after any change in rate or sooner if clinically required by the patient.
  • Check APTT every 24hrs if no change made to the infusion rate

Prophyaxis with low molecular weight heparin

Prevention of venous thromboembolism is a quality initiative of great importance. As well as forming a key patient safety initiative, the assessment treatmtent of patients for VTE risk is a national target. Guidance on prophylaxis regimes for medical, surgical, and obstetric and gynaecology patients can be found in Sharepoint.

Treatment with low molecular weight heparin

Low molecular weight heparin, TINZAPARIN, is licensed for the treatment of DVT and PE

Confirm diagnosis objectively in all cases but do not delay anticoagulant treatment.

Treat according to following guidance:

i.Tinzaparin subcutaneously once daily (see table below) or IV unfractionated heparin (see subsection on intravenous heparin)

ii.Warfarin should be commenced on the first day unless there is some doubt concerning the diagnosis (see warfarin subsection).

NB: Some patient groups for example, those imminently undergoing surgery or with a diagnosis of cancer will remain on LMWH rather than be treated with warfarin.

iii.In some cases, for example life threating pulmonary embolus, an Initial loading dose of standard heparin 5000 unitsmay be administered intravenously over 5 minutes.

Renal Function

Renal function must be considered when prescribing treatment doses of LMWH for patients. The renal function test should not delay initiation of the first dose but every effort must be made to base subsequent dosing on these results. Renal function tests should be carried out in accordance with the standard processes in place at COCH.

If creatinine clearance drops below 30 ml/min while the patient is on therapeutic tinzaparin, consider monitoring with anti-Xa or, switching to enoxaparin which has a renal adjusted dose. Anti-Xa levels should also be monitored with the aim of achieving levels of anti-Xa 0.4 – 0.8iu/ml as a therapeutic target.

Tinzaparin Dosage Schedule

The recommended dose of Tinzaparin is 175 units/Kg administered subcutaneously in a single daily dose, (but see risks and warnings below).

Patients must be weighed, and their weight recorded before a dose of tinzaparin is prescribed. If patients weight changes or is likely to change to the extent that a change in dose of tinzaparin is required during their admission, their weight should be re-measured and doses adjusted accordingly.

The treatment table should be used to dose band the patient’s dose accoding to their weight.

Treatment with Tinzaparin should continue in parallel with oral warfarin for at least 6 days OR until the patient’s INR is > 2.0 for two consecutive days, whichever is longer.

Tinzaparin should be prescribed in units

Some patients require a twice daily dosing regime: a consultant haematologist will advise, e.g. some patients in pregnancy, some patients with malignant disease

The abdominal lateral flank is the preferred injection site, not into the arms or thigh.

In most circumstances, monitoring of APTT is inappropriate whilst the patient is on LMWH. Some patients require anti-Xa levels to assess the level of anticoagulation (e.g. renal impairment, pregnant patients and some patients with malignancy): Please contact the anticoagulation team if monitoring is required.

Therapeutic dose of Tinzaparin

Patient’s Weight
Kg / Tinzaparin dose
175 IU/kg / Number of mls injected subcutaneously / Syringe to use
32 - 37 / 6,000 units / 0.30ml / RED 0.5ML
SYRINGE
38 - 42 / 7,000 units / 0.35ml
43 - 48 / 8,000 units / 0.40ml
49 - 54 / 9,000 units / 0.45ml
55- 59 / 10,000 units / 0.50ml
60 - 65 / 11,000 units / 0.55ml / YELLOW
0.7ML
SYRINGE
66 - 71 / 12,000 units / 0.60ml
72 - 77 / 13,000 units / 0.65ml
78 - 82 / 14,000 units / 0.70ml
83 - 88 / 15,000 units / 0.75ml / BLUE
0.9ML
SYRINGE
89 - 94 / 16,000 units / 0.80ml
95 – 99 / 17,000 units / 0.85ml
100 - 105 / 18,000 units / 0.90ml
105+ / Continuing dosing at
175 IU/kg / Use the GREEN vial
(40,000 i.u/2ml) some patients merit B.D. dosage: take advice from anticoagulant clinic
(NB: contains benzyl alcohol as a preservative so MUST NOT be used in pregnant women. Use prefilled syringes to administer the equivalent dose) / GREEN 2ML VIAL

Risks and warnings for treatment with tinzaparin

Known hypersensitivity to Tinzaparin / Uncontrolled severe hypertension
Bacterial endocarditis / If regional anaesthesia is planned
History of heparin induced thrombocytopenia
/ Recent G.I. bleed or surgery: reconsider need for anticoagulation
Concurrent NSAIDS or aspirin / Renal impairment: dose reduction required

Monitoring

Bleeding is a complication of heparin (both unfractionated low molecular weight) treatment which can be reversed using a protamine infusion. See the Joint Medicines Formulary for recommended doses or the consultant haematologist on call if necessary.

Heparin induced thrombocytopenia (HIT)is also a complication of heparin treatment and is an indication for immediate cessation of treatment. It is an immune response and is not dose related When starting heparin treatment, a baseline platelet count should be established and then monitored thereafter while being treated with heparin.

Details of the treatement of HIT can be found in the Sharepoint Document “Heparin Induced Thrombocytopenia (HIT) – Administration of Danaparoid and Fondaparinux”.

The greatest risk of HIT is in the first two weeks after starting heparin. Patients platelet levels should be checked between 4 and 14 days after therapy has started unless they have previous exposure to heparin in which case platelets should be checked after 24 hours.

Protamine

Protamine sulphate is used to treat over dosage of heparin, and low molecular weight heparins. The long half life of low molecular weight heparin should be taken into consideration when determining the dose of protamine sulphate; the effects of low molecular weight heparins can last up to up to 24 hours after administration. Excessive doses of protamine can have an anticoagulant effect. The BNF gives advice on doses of protamine in different clinical circumstances and can be found in section 2.8.3. More detailed advice can be found on the product SPC located at

New Oral Anticoagulants (NOACs)

Dabigatran, rivaroxaban and apixaban are NOACs which are licensed to be used in non-valvular atrial fibrillation (AF) with one or more risk factors as per individual NICE TA’s. They are an alternative anticoagulant agent when warfarin is poorly tolerated due to adverse reactions or labile INRs. Warfarin remains the first line anticoagulant of choice – see Trust AF Thromboprophylaxis Guidelines.

Rivaroxaban is also used in the Treatment of DVT & PE and is approved by NICE for this purpose. See NICE TA 261, NICE TA 287and the COCH DVT pathway.

Renal function should be assessed prior to initiation to assess suitability of each agent - see prescribing guidance. While on treatment with NOACs, renal function should be assessed in clinical situations where it is suspected that function could decline or deteriorate. Consider temporarily substituting a NOAC with prophylactic LMWH in patients who are admitted to hospital with sepsis, acute kidney injury, hypovolaemia, dehydration or who are started on high dose diuretics.

There is no routine monitoring required for NOACs. There is no reliable method to quantify the anticoagulant effect, INRs are not clinically relevant. Bleeding may occur at any site during therapy with NOACs. An unexplained fall in haemaglobin and/or haematocrit, blood pressure or other clinical features suggestive of bleeding should lead to further investigation. Close clinical supervision is recommended throughout the treatment period, especially if risk factors are combined. There is no reversal agent currently available, patients must be informed by the clinician before initiation of a NOAC – see Trust Guidelines for Management of Bleeding with NOACs. Patient information leaflets are available to aid in this discussion.

Dabigatran, rivaroxaban and apixaban have different licensing and are appropriate for different patient groups. Prescribing information is available for each agent on the Trust AF Thromboprophylaxis Guidelines. All prescribing must follow Trust guidance and the prescribing checklist must be completed and signed for each agent.

For orthopaedic surgery, the Trust’s drug of choice is Apixiban etc.

Prescribing warfarin.

Warfarin must be prescribed in whole milligrams and not using 0.5mg or other incremental doses. Dosage recommendations should:

use the least number of tablets each day

use constant daily dosing and not alternate day dosing unless unavoidable

not require the use of half tablets

Local policy, is to use the 5mg tablets for loading doses of 5mg or 10mg and 3mg &1mg tabletsfor ongoing treatment. Please note that 5mg (except for loading) and 0.5mg tablets are not routinely issued at COCH. Should clinical situations dictate that 5mg & 0.5mg tablets are appropriate for individual patients, they may be used following discussionwith the ward / clinical pharmacist an assessment of whether this may cause patients to be confused about dosing.

Starting warfarin

1.Establish target INR using the table below:NB: See BMJ e-learning module

Clinical indication / Target INR& range / Recommended Duration
Calf DVT post-op, no risk factors / 2.5 (2 to 3) / 6 weeks
Calf DVT non-surgical patient, no risk factors / 2.5 (2 to 3) / 13 weeks
DVT, persistent risk factors / 2.5 (2 to 3) / Indefinite whilst risk factors persist
PE or Proximal DVT / 2.5 (2 to 3) / 26 weeks. In the case of an unprovoked event, the patient needs to be reviewed regarding need for indefinite anticoagulation.
Uncomplicated
post-op PE / 2.5 (2 to 3) / 13 weeks
Recurrent DVT/PE, with an in-range INR of 2 to 3 whilst on warfarin / 3.5 ( 3 to 4) / Indefinite
Antiphospholipid Syn - adjust to target on individual basis. / Indefinite
AF(& other arrhythmia) / 2.5 (2 to 3) / Indefinite
AF for Cardioversion / 3.0 (2.5 to 3.5) / Until advised by Cardiologist
AF with TIA / 2.5 (2 to 3) / Indefinite
Mechanical prosthetic valves (choice of two ranges - please specify) / As guided by the surgical centre responsible for the valves / Indefinite
Bioprosthetic valves-mitral / 2.5 (2 to 3) / 13 weeks: discontinue Warfarin after 3 months if no AF or embolism : convert to aspirin.
Cardiomyopathy, mural thrombosis / 2.5 (2 to 3) / Indefinite
NB: Antiplatelets are first line therapy, usually indefinitely, for the following conditions. If you wish to anti-coagulate, get advice from the anticoagulation team: /
  • Ischaemic stroke (not AF),
  • Peripheral arterial thrombosis and grafts
  • Coronary artery thrombosis/ graft thrombosis

2. Establish a baseline INR to ascertain whether the patient is suitable for warfarin.

3. Choose one of the regimes listed below depending on the indication and using an assessment of whether the chosen regime appears to match the patient’s clinical condition.

Regime 1 - Rapid anticoagulation:(e.g. VTE) Use the modified Fennerty regime below. Do not use in patients over 65 years of age, with atrial fibrillation.
Day / INR / Dose (mg)
1 / Baseline INR required
<1.4
1.4 to 2.0 / 10
5
2 / No INR required / Dose as per day 1.
3 / <1.6
1.6 -1.9
2.0 -2.1
2.1 to 2.5
2.6 to 2.9
3.0 to 3.3
3.4 to 3.5
>3.5 / 10
7
5
4
3
2
1
nil
4 / <1.4
1.4 to 1.7
1.8 to 2.0
2.1 to 2.3
2.4 to 3.0
3.1 to 4.0
4.1 to 4.5
>4.5 / Ask advice
8
6
5
4
3
Miss 1 dose then give 2mg
Miss 1 or more doses
5. Monitor until stable. NB: if in doubt take your consultant’s advice or ask a haematologist.

Regime 2 - Slow loading: E.g. for atrial fibrillation or other non-urgent indications

NB: A baseline INR must be obtained and reviewed before prescribing 3mg warfarin for seven days.
Day 1: Baseline INR required
Day 1-7: Prescribe warfarin 3mg daily, for seven days
Day 8: Check INR

4. Complete an anticoagulant chart.

Before prescribing warfarin, enter the:

reason for warfarin therapy

target INR

duration of treatment:

patient’s usual dose of warfarin (if known)

5a. If the patient is to start warfarin therapy as a new treatment

Document on the chart if:

The patient has been informed about & agreed to therapy?

The patient has been given a yellow anticoagulation book?

A baseline INR has been measured & recorded?

5b. If the patient is already taking warfarin therapy

Document on the chart if:

The patient’s yellow book has been checked for information about usual dosing

The INR has been checked on admission, before prescribing?