Pulmonary embolism (Guidelines)

In cardiac arrest/ peri-arrest

Assess for any contra-indications to thrombolysis (if feasible) and proceed to thrombolysis if clinically indicated and approved by a senior clinician.

Give alteplase 50mg as a bolus over 1 to 2 minutes. In cardiac arrest, a further 50mg may be administered as an IV bolus, whilst in a peri-arrest which doesn’t progress to cardiac arrest, give a further 50mg as an IV infusion over 2 hours.

NB dosing in cardiac arrest / peri-arrest is unlicensed.

In haemodynamically unstable patients (not cardiac arrest/ peri arrest):

Assess for any contra-indications to thrombolysis and proceed to thrombolysis if clinically indicated and approved by a senior clinician.

Give alteplase as per table below:

Injectable Medicines Guide access:

• IV monograph accessed via NHS Injectable Medicines Guide – Alteplase (Medusa) (NHS Highland intranet access required).
• Direct link: NHS Injectable Medicines Guide (password protected, available via Medicines Information).
• Also available via the Clinical Applications page of the NHS Highland intranet. 

Absolute contra-indications to thrombolysis include:

• Intracranial neoplasm
• Recent (<2 months) intracranial or spinal surgery or trauma
• History of a haemorrhagic stroke
• Active bleeding or bleeding diathesis (eg, severe thrombocytopenia)
• Treatment with anticoagulant
• Or non-haemorrhagic stroke, within the previous three months.

Relative contra-indications to thrombolysis include:

• Severe uncontrolled hypertension (systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg)
• Non-haemorrhagic stroke more than three months prior
• Surgery within the previous 10 days
• Pregnancy
• Haemorrhagic or ischaemic stroke in preceding 6 months

Complete drug information: Actilyse 10 mg powder and solvent for solution for injection and infusion - Summary of Product Characteristics

Following thrombolysis, patients should be stepped down to unfractionated heparin (UFH) or treatment dose low molecular weight heparin (LMWH). This decision should be based on clinical response to thrombolysis, and individual bleeding risk. UFH should only be administered in level 2 or 3 settings.

Step down to unfractionated heparin (UFH) for 24 – 48 hrs

If the patient has had LMWH within the previous 12 hours:

• DO NOT give a bolus dose, but commence UFH via continuous infusion.
• Prescribe on the “Unfractionated Heparin (UFH) Prescription Chart for Intravenous (IV) Infusion", available in critical care areas.
• Ensure UFH is also prescribed on the Kardex, “as per chart” or via the placeholder on HEPMA "HEPARIN Infusion - AS PER PAPER CHART".
• The suggested dose is 18 units/kg/hour but doses are weight banded on the prescribing chart for ease of use.

If the patient has NOT had LMWH within the previous 12 hours:

• Give a bolus dose of UFH 75 units/kg over 3 to 5 minutes. Doses are weight banded on the prescribing chart for ease of use.
• Prescribe on the “Unfractionated Heparin (UFH) Prescription Chart for Intravenous (IV) Infusion”, available in critical care areas.
• Ensure UFH is also prescribed on the Kardex, “as per chart” or via the placeholder on HEPMA "HEPARIN Infusion - AS PER PAPER CHART".
• Immediately following the bolus dose, commence UFH via continuous infusion.

Monitoring whilst on UFH

• Check APTT ratio 4 hours after commencing UFH and adjust dose as per Unfractionated (UF) Heparin Prescription Chart for Intravenous (IV) Infusion.
• Check APTT ratio 4 hours after any adjustment is made to the infusion rate.
• Once stable, check APTT ratio 12 hourly during treatment.

Step down to LMWH

Enoxaparin is the LMWH of choice in NHS Highland. The first dose of enoxaparin should be given immediately post thrombolysis, unless there are any immediate signs of bleeding. If patients were already prescribed treatment dose enoxaparin prior to thrombolysis, check dosing below, and restart LMWH.

The maximum single dose of enoxaparin is 120mg. In patients who weigh >120kg, start with 120mg every 12 hours (provided CrCl ≥ 30mL/min), and seek specialist haematology advice +/- monitoring of factor Xa levels.

Step down to oral therapy

When stepping down from UFH to apixaban, stop the continuous infusion and give the first dose of apixaban at the same time.

When stepping down from treatment dose LMWH to apixaban, give apixaban at the next scheduled dose of LMWH. Do NOT give LMWH at the same time and ensure LMWH is discontinued on the Kardex or HEPMA.

More detailed information on anticoagulant switching is available: Anticoagulant switching | Right Decisions

For more details on apixaban prescribing, see section “Direct oral anticoagulants”

First-line option:

Apixaban

• 10mg twice daily for 7 days, THEN
• 5mg twice daily for at least 3 months (See: Treatment duration and follow-up)

Detailed drug information, including dose adjustments for weight and renal function: Apixaban 5mg Film-Coated Tablets - Summary of Product Characteristics (SmPC)

Second-line options:

Rivaroxaban

• 15mg twice daily for 21 days, THEN
• 20mg once daily for at least 3 month (See: Treatment duration and follow-up)
• NB rivaroxaban must be taken with food

Detailed drug information, including dose adjustments for weight and renal function: Xarelto 15mg film-coated tablets - Summary of Product Characteristics (SmPC)

Dabigatran and edoxaban.

• Note: Requirement for 5 days of treatment dose LMWH before initiating dabigatran or edoxaban for PE.
• See SPC’s for detailed prescribing information.

Notes: 

• All patients commenced DOAC should have their medications reviewed to check for significant drug interactions and drugs which may be associated with a cumulative bleeding risk:
  • Check detailed drug interaction information at Medicines Complete — Stockley's Interactions Checker
  • Antiplatelets: consider stopping, unless clear indication to continue antiplatelet in combination with DOAC. Consider discussing with Cardiology, where appropriate. Document rationale for co-prescribing
  • NSAID’s: bleeding risk, avoid where possible. If short term use required, ensure limited duration and GI protection considered
• All patients initiated on DOAC should receive verbal and written information prior to discharge, see: DOAC Counselling Tool (NHS Highland intranet access required)

DOAC contra-indicated or unsuitable at present:

Low Molecular Weight Heparin (LMWH): Enoxaparin, prescribed as per guidance above. 

Treatment Duration

Provoked PEs (transient/ reversible risk factor)

• Discontinue anticoagulation after 3 months (6 months in active cancer)

Unprovoked or recurrent PEs:

• Continue anticoagulation for at least 6 months and refer to PE clinic

Follow-up

Patients who should be referred to the PE service for follow-up include:

• All patients under the age of 50 with PE
• All unprovoked PE
• Recurrent PE
• All intermediate-high and high risk PE, as determined by the Risk Stratification above

Treatment duration >6 months may be appropriate for high risk / recurrent PE patients. Final decision will be made at PE clinic.

The investigation and management of PE in pregnancy falls outwith this guidance and therefore should NOT be used.

Please contact Obstetrics / Gynaecology urgently if a pregnant patient presents with suspected or confirmed PE.

Pulmonary Embolism service referral form (NHS Highland intranet access required). 

• APTT: Activated partial thromboplastin time
• BP: Blood pressure
• CCU: Coronary Care Unit.
• CrCl: Creatinine clearance.
• CTPA: Computed tomography pulmonary angiography
• DVT: Deep vein thrombosis
• DOAC: Direct oral anticoagulants
• GI: Gastrointestinal
• HEPMA: Hospital Electronic Prescribing and Medicines Administration
• IV: Intravenous
• LMWH: Low‑molecular‑weight heparin
• MHDU: Medical High Dependency Unit
• NSAIDs: Non-steroidal anti-inflammatory drugs
• PE: Pulmonary embolism
• RV: Right ventricular
• SmPC: Summary of Product Characteristics
• sPESI: Simplified Pulmonary Embolism Severity Index
• UFH: Unfractionated heparin