1. Clinical Knowledge Summaries CKS Pulmonary embolism (PE)
Diagnosis and management in primary care.
Educational slides based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

2. Key learning points and objectives
To be able to
Recognise people who are considered to be at high risk of PE and need immediate admission.
Assess the likelihood of a of a PE using the two-level PE Wells score.
Describe when it is appropriate to give a parenteral anticoagulant and which one should be offered.
Outline what management and follow up is required after discharge from hospital.

3. PE – background information
A PE is where one or more emboli are lodged in and obstruct the pulmonary arterial system.
The annual incidence of PE is around 3–4 per 10,000 people.
A PE may be:
Provoked – associated with a transient risk factor (e.g. significant immobility, surgery).
Unprovoked – no identifiable risk factor or a risk factor that is persistent and not easily correctable (e.g. active cancer).
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

4. Sources of emboli
The most common source is deep vein thrombosis (DVT) in the lower limbs (80%).
Other sources include:
Emboli originating in the abdominal or axillary veins, or from the right ventricle.
Tumours – mostly prostate and breast cancer.
Fat from long bone fractures.
Amniotic fluid – pregnant women.
Sepsis – e.g. infected indwelling catheters.
Foreign bodies (e.g. during IV drug use).
Air – admitted during surgery.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

5. Major risk factors for PE
Major risk factors include:
Deep vein thrombosis (DVT).
Previous DVT or pulmonary embolism.
Active cancer.
Recent surgery, hospitalization, lower limb trauma, or other immobilization (including long-distance sedentary travel).
Pregnancy, in particular 6 weeks postpartum.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

6. Other risk factors Other risk factors include:
Increasing age (older than 60 years of age).
Combined oral contraception and hormone replacement therapy.
Obesity (body mass index greater than 30 kg/m2).
One or more significant medical comorbidities (e.g. heart disease, acute infectious disease, inflammatory conditions).
Varicose veins.
Superficial venous thrombosis.
Known thrombophilias.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

7. What else might it be?
Other conditions that could mimic the symptoms of a PE include:
Respiratory conditions (e.g. pneumothorax).
Cardiac conditions (e.g. acute coronary syndrome).
Musculoskeletal chest pain.
Gastro-oesophageal reflux disease.
Pregnancy.
Any cause for collapse such as vasovagal syncope.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

8. Complications Mortality
Untreated, the risk of death from a PE is high (23–87%).
When treated with heparin and anticoagulants the risk of death ranges from 2-6%.
For a clinically massive PE the risk of death is about 50%.
PE is the leading cause of maternal deaths in the UK.
Chronic thromboembolic pulmonary hypertension (CTEPH)
Occurs in 0.5–5% of people with treated PE.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

9. When to suspect a PE Suspect a PE if the person has:
Dyspnoea, tachypnoea, pleuritic chest pain, or features of a DVT.
These features are present in 97% of people with PE, but
Only 15% of people with a PE have signs of DVT.
Other features such as tachycardia, haemoptysis, syncope, hypotension (systolic BP less than 90 mmHg), crepitations, cough or fever.
A risk factor for PE (e.g. previous DVT/PE, pregnant).
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

10. When to suspect a PE To exclude an alternative cause:
Carry out a physical examination.
Review the person's general medical history.
ECG or chest X-ray
Are of limited value as they are usually normal in someone with a PE.
May be done as part of investigations for breathlessness or chest pain when another diagnosis seems more likely.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

11. Managing a suspected PE
Arrange immediate admission if the person is:
Pregnant or has given birth within the past 6 weeks.
It is not possible to accurately assess the risk of PE in primary care.
Severely ill with:
Altered level of consciousness.
Systolic BP of less than 90 mm Hg.
Heart rate of more than 130 beats per minute.
Respiratory rate of more than 25 breaths per minute.
Oxygen saturation of less than 91%.
Temperature of less than 35°C.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

12. Managing a suspected PE
For all other people use the two-level PE Wells score to assess likelihood of PE and inform further management.
Using this score a PE is:
Likely if the score is more than 4 points.
Unlikely if the score is 4 points or less.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

13. Using the two level PE Wells score
Scoring is as follows:
Score 3 points if:
There are clinical features of a DVT.
An alternative diagnosis is less likely than a PE.
Score 1.5 points if:
Heart rate is greater than 100 beats per minute.
Immobilization for more than 3 days.
Surgery in the previous 4 weeks.
Previous DVT or PE.
Score 1 point if the person has:
Haemoptysis.
Cancer.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

14. If PE likely (>4 points)
Arrange immediate admission for a computed tomography pulmonary angiogram (CTPA), or
If there will be a delay in the person receiving a CTPA:
Give immediate interim low molecular weight heparin (LMWH) or fondaparinux, and
Arrange hospital admission.
Body weight is required to prescribe LMWH or fondaparinux.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

15. If PE unlikely (4 points or less)
Arrange a D-dimer test.
If the D-dimer test is positive:
Arrange admission to hospital for an immediate CTPA, or
If a CTPA cannot be carried out immediately, give LMWH or fondaparinux and arrange hospital admission.
If the D-dimer test is negative, consider an alternative diagnosis.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

16. Which parenteral anticoagulant?
Offer a choice of low molecular weight heparin (LMWH) or fondaparinux.
Licensed LMWHs for DVT treatment include dalteparin, enoxaparin, and tinzaparin.
Fondaparinux is a synthetic pentasaccharide that inhibits activated factor X.
Choice of parenteral anticoagulant depends on:
Comorbidities, contraindications, and cost.
Local policy may also influence choice.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

17. Treatments in secondary care
Once a PE has been confirmed in secondary care, most people will be initiated on long term treatment with either:
An oral anticoagulant (warfarin or rivaroxaban), or
A LMWH.
LMWH are usually indicated if oral anticoagulants are:
Contraindicated, for example pregnancy, or
Less preferred, for example cancer
Thrombolytic therapy or embolectomy may be offered to people who are not haemodynamically stable.
Presenter notes
Bridging therapy with heparin or a low molecular weight heparin is given concomitantly if warfarin therapy is initiated. This is because it can take 48 to 72 hours (or longer) for the anticoagulant effect of warfarin to fully develop (CKS topic Anticoagulation – oral; May 2013).
Rivaroxaban has a faster onset of action of 2-4 hours (Rivaroxaban monograph, Micromedex; last updated March 2014).
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

18. Duration of treatment
Specialists will usually decide on the duration of treatment, however in general:
Treatment is usually continued for 3 months in people with a provoked PE.
Treatment is continued for more than 3 months in people with an unprovoked PE.
For pregnant women
LMWH is continued until the end of pregnancy (unlicensed use).
For people with active cancer
LMWH is continued until the cancer is considered cured or for at least 6 months.
Dalteparin licensed for long term use in people with solid tumours.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

19. What is the risk of recurrence?
Risk of recurrence depends on individual risk factors, but in general:
Recurrence is lower for people with a provoked PE (compared with unprovoked).
Without treatment - the risk of recurrence is approximately 50%.
With treatment (3 months of anticoagulation) - the risk of recurrence is around 8%.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

20. Follow up for PE For people with an unprovoked PE:
Investigate for the possibility of an undiagnosed cancer if they are not already known to have cancer.
Apparent unprovoked venous thromboembolism is associated with a significant increase in the risk of cancer (11%) within the first 1-2 years.
Consider antiphospholipid testing before stopping anticoagulants.
Consider arranging hereditary thrombophilia testing if there is a first-degree relative who has had a DVT or PE.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

21. Follow up for PE
Ensure adequate regular monitoring for warfarin or rivaroxaban.
Monitoring requirements for warfarin and rivaroxaban differ.
Based on the CKS topic Pulmonary embolism (June 2013), and NICE guidance (2012a): Venous thromboembolic disease: the management of venous thromboembolic diseases and the role of thrombophilia testing.

22. Monitoring warfarin
Monitor the international normalized ratio (INR) and adjust the dose as required.
The target INR for people with a PE is between 2 and 3 (ideally 2.5).
Usually monitor INR:
Initially - daily, or every other day, until within therapeutic range, then
Twice weekly for 1–2 weeks, then
Weekly until at least two INR measurements are within range, thereafter
Depends on the stability of the INR but usually longer intervals (e.g. up to every 12 weeks).
Based on the CKS topic Anticoagulation – 0ral (May 2013)

23. Monitoring rivaroxaban
No need to monitor the INR, however
Regular follow up and monitoring is still required.
Follow up every 3 months to assess for:
Compliance and adverse effects (e.g. bleeding).
Repeat renal and liver function tests as well as the full blood count at least once a year.
Repeat renal function tests:
Every six months if the person has a creatinine clearance (CrCl) of 30–60 mL/min.
Every three months if the person has a CrCl of 15–30  mL/min.
If renal function has declined, review treatment
Rivaroxaban may need to be stopped or the dose lowered.
Based on the CKS topic Anticoagulation – 0ral (May 2013)

24. Summary
The most common source of PE is a DVT in the lower limbs (80%).
Untreated, the risk of death from a PE is high (23–87%).
When treated with heparin and anticoagulants the risk of death ranges from 2-6%.
Arrange immediate admission if the person is:
Pregnant or has given birth within the past 6 weeks.
Severely ill with, for example altered level of consciousness.
For every one else use the two-level PE Wells score to assess likelihood of PE. A PE is:
Likely if the score is more than 4 points.
Unlikely if the score is 4 points or less.
If PE is likely - arrange immediate admission for a CTPA, or if there will be a delay in the person receiving a CTPA:
Give immediate interim low molecular weight heparin (LMWH) or fondaparinux, and arrange hospital admission.
If PE is unlikely - arrange a D-dimer test, if the D-dimer test is positive:
Arrange admission to hospital for an immediate CTPA, or
If a CTPA cannot be carried out immediately, give LMWH or fondaparinux and arrange hospital admission.