Pulmonary Embolism

Author: Steven Crane, Jason Lee, Francis Morris / Editor: Jason M Kendall, Emer Kidney / Reviewer: Eugene Henry / Codes: A2 / Published: 18/05/2023

Context

The annual incidence of Pulmonary Embolism (PE) is about 60-70/100,000. Patients undergoing hip or knee replacement surgery, surgery for lower limb fractures and cancer surgery are at particular risk. However, the largest numbers of thromboembolic events occur in patients hospitalised for acute medical illness1. It is estimated that 25,000 patients die every year in the UK from preventable hospital acquired venous thromboembolism (VTE)2. Amongst those not in hospital or long term care, patients who suffer from thromboembolism are more or less equally divided between those who have identifiable risk factors and those who suffer from idiopathic PE. The in-hospital mortality for pulmonary embolus ranges from 6% to 15%3,4.

PE is an important and difficult diagnosis to make confidently since it cannot be either confirmed or excluded on clinical grounds alone. The diagnosis is frequently overlooked in hospitalised, older patients with multiple co-morbidities and the majority of fatal pulmonary emboli are not clinically suspected prior to death. Conversely, Wells reported5 that only 9.5% of those patients presenting with symptoms suggestive of the diagnosis, were finally determined to have suffered a pulmonary embolus. The importance of getting the diagnosis right is that treatment leads to about a 20% reduction in mortality. Accurate diagnosis is also essential to prevent the unnecessary provision of anticoagulation therapy which is associated with a range of serious side effects.

The UK National Institute of Clinical Excellence (NICE), the European Society of Cardiology, the American College of Emergency Physicians, the American Heart Association and the American College of Chest Physicians have all published guidelines on the management of patients with suspected PE. The UK NICE guidelines on the subject, last updated in 2020 can be found here.

Basic science and pathophysiology

Pulmonary embolism should be regarded as a complication of underlying venous thrombosis. In the normal situation, tiny microthrombi are continually formed and lysed in equal measure within the venous circulatory system i.e. there is a balance between the thrombotic and fibrinolytic systems. In some pathological situations, microthrombi escape the fibrinolytic system and are allowed to propagate into larger thrombi.

The predisposing factors that may underlie this change can be broadly described under the three headings of Virchow’s Triad:

  • Venostasis
  • Hypercoagulability
  • Vessel wall inflammation

All known clinical risk factors for venous-thromboembolism have their basis in one of these three factors.

virchowstriad

Most pulmonary emboli occur when fragments of a thrombus break free from the deep venous system, typically in the pelvis and lower limb, travel up the vena cava, through the right atrium and into the pulmonary vasculature. 79% of patients with proven pulmonary emboli also have thrombus detectable in the leg or thigh6. Although clots can also form in the upper arm veins they rarely embolise, and when they do they tend to cause smaller, less significant pulmonary emboli.

The lungs act as a filter for all blood returning to the heart so all but the smallest clots will get stuck there rather than travelling to the arterial circulation. The lungs have a dual blood supply from both the pulmonary artery and bronchial arteries which helps them recover function after small pulmonary emboli.

Provoked pulmonary embolism is a pulmonary embolism associated with a transient risk factor such as significant immobility, surgery, trauma, and pregnancy or puerperium.

Unprovoked pulmonary embolism is a pulmonary embolism occurring in the absence of a transient risk factor. The person may have no identifiable risk factor or a risk factor that is persistent and not easily correctable ( NICE CKS PE).

In massive PE (i.e. more than 50% obstruction of the pulmonary vascular bed) the most immediate problem is usually circulatory collapse due to a fall in cardiac output as the right heart fails to pump an adequate volume of blood through the reduced pulmonary vasculature to the left side of the heart.

In younger patients with normal cardiopulmonary function, oxygen saturations may be correctable with high flow oxygen as all of the blood getting to the left heart is still passing through good quality lung tissue giving good oxygenation. However, in patients with underlying lung pathology such as COPD a non-massive PE may present major problems with maintaining oxygenation despite the absence of haemodynamic compromise, as the function of the lung unaffected by the PE is already impaired.

Patients with a PE may present to the Emergency Department in a variety of ways, and the key to successful diagnosis is to consider it as a possible cause of your patients symptoms.

Patients with pulmonary emboli usually fall into one of three characteristic presentations:

Massive PE

(uncommon) where the patient is clinically shocked and hypoxic.

Usually, the clinical diagnosis is straightforward, though conditions such as right ventricular infarction, sepsis and concealed upper gastrointestinal haemorrhage can give present in a similar fashion.

The risk of death within 90 days is about 50%.

Sub-massive PE

(<50% obstruction of the pulmonary vascular bed) in which the patient has acute dyspnoea and frequently chest tightness/pain. The differential diagnosis in these patients includes acute coronary syndromes, pneumonia and heart failure.

Pulmonary Infarction

The patient commonly presents with pleuritic chest pain, which may be associated with haemoptysis (uncommon) and/or dyspnoea. It is usually in this low risk group of patients where most diagnostic difficulty exists. The differential diagnosis on this group of patients includes musculoskeletal pain, pleurisy, viral and bacterial infections, pericarditis and a pneumothorax.

The clinical examination should specifically focus upon looking for signs indicative of a deep venous thrombosis and conditions that may masquerade as a pulmonary embolism such as pneumonia (e.g. pyrexia, bronchial breathing). Classically, in patients with a PE chest examination reveals no abnormality.

In addition, patients should be examined for possible underlying causes of venous thromboembolism such as cancer (e.g. organomegaly, lymphadenopathy).

Clinical features

Recognised clinical features found in patients with a PE are shown below:

Table 1: Clinical features of PE
Clinical features of PE in descending order of frequency:
1 Dyspnoea (70% of patients)
2 Tachypnoea (RR>20)
3 Pleuritic chest pain
4 Apprehension
5 Tachycardia (>100bpm)
6 Cough
7 Haemoptysis
8 Leg pain
9 Clinically evident DVT (10% of patients)

Less than 10% of patients with PE have none of the top three symptoms of dyspnoea, tachypnoea and pleuritic chest pain. However, none of these typical presenting features are pathognomic of pulmonary embolus and some patients with PE present with more subtle symptoms or atypical symptoms such as syncope or postural hypotension.

With subacute PEs the diagnosis is particularly difficult to make as the patient may complain of gradually increasing dyspnoea or worsening exercise tolerance, rather than sudden acute symptoms.

Risk factors

In addition to a clear description of the presenting symptoms it is also necessary to ascertain if any risk factors for PE are present.

The British Thoracic Society 20037 splits these into major and minor risk factors. The presence of a major risk factor conveys a 5-20 times increased risk of a PE to the patient whilst a minor factor conveys a 2-3 times increased risk (Table 1).

Similarly, NICE guidelines suggest that risk factors for VTE include a prior history of DVT, age over 60 years, surgery, obesity, prolonged travel, acute medical illness, cancer, immobility, thrombophilia (an abnormal tendency for the blood to clot) and pregnancy.

Table 2: Risk factors for PE
Major risk factors (relative risk 5-20)
Surgery Major abdominal/pelvic surgery
Hip or knee replacement
Post operative intensive care
Obstetrics Late pregnancy
Caesarian section
Puerperium
Lower limb problems Fracture
Varicose veins
Malignancy Abdominal/pelvic
Advanced/metastatic
Reduced mobility Hospitalisation
Institutional care
Previous proven venous thromboembolism
Minor risk factors (relative risk 2-4)
Cardiovascular Congenital heart disease
Congestive cardiac failure
Hypertension
Superficial venous thrombosis
Indwelling central vein catheter
Oestrogens Oral contraceptive
Hormone replacement therapy
Miscellaneous COPD
Neurological disability
Occult malignancy
Thrombotic disorders
Long distance sedentary travel
Obesity

A full list of risk factors can be viewed here.

Chest Radiograph

A chest radiograph should be requested for all patients with a suspected PE. It is usually normal or may reveal non-specific changes such as small pleural effusion. Rarely, a wedge shaped pulmonary infarction (see Fig 1 below) or regional oligaemia (Westermark sign) may be seen.

plainchestradiograph-1

Fig 1: Plain chest radiograph showing classical peripheral wedge shadow of pulmonary infarction

Learning Bite

The main purpose of the chest radiograph is to exclude alternative diagnosis, for example, pneumothorax or infection which may give rise to the same presenting symptoms.

12-Lead ECG

An ECG should be obtained to look for signs supportive of right heart strain such as right axis deviation, and to rule out an acute coronary syndrome. The most common ECG finding is a sinus tachycardia. Atrial fibrillation is present in approximately 20% of cases.

The classical S1 Q3 T3 pattern (below) reflects right heart strain and is only present in 10% of patients.

ECGshowingclassical

Blood Tests

  • Arterial Blood Gas (ABG): ABG analysis may confirm hypoxia, evidence of hyperventilation and an increased Arterial-alveolar gradient. Whilst supportive of a pulmonary embolism these features are not exclusive to this condition and may be found in conditions such as pneumonia.
  • Full blood count: A full blood count may reveal a marked neutrophilia which may suggest a diagnosis of infection rather than infarction.
  • Cardiac troponin: Troponin levels may be elevated in acute PE, particularly massive PE. High levels suggest right ventricular strain or overload and can be helpful in prognosis and risk stratification (e.g. as an aid to decision making for thrombolysis in PE), but are not useful in the diagnosis of PE8.

Learning Bite

Neither a chest radiograph nor any of the tests listed above are sensitive or specific enough to rule in or exclude a diagnosis of PE.

Risk Stratification and further investigations

The information obtained from the history, examination and investigations performed in the ED will identify a group of patients in whom an alternative diagnosis can be confidently made thereby precluding the need for further investigation for PE.

For those patients in whom an alternative diagnosis cannot confidently be made, risk stratification (using information in the history and examination) must be performed to assign a clinical probability of PE to the patient and to determine the best strategy for excluding PE.

The most widely used risk stratification tools are:

  • Wells criteria5
  • Revised Geneva Score9 or Simplified Revised Geneva Score10
  • Pulmonary Embolus Rule-Out Criteria (PERC)11

Wells Criteria

Table 1: Wells’ criteria
Clinically suspected DVT 3.0
PE at least as likely or more likely than alternative diagnosis 3.0
Pulse rate >100 1.5
Immobilisation >3 days 1.5
Surgery last 4 weeks 1.5
Previous VTE 1.5
Haemoptysis 1.0
Malignancy 1.0

Wells criteria is a semi-objective way of predicting pre-test probability in a patient with a possible PE.

In the original score patients were divided into three risk groups:

  • Patients scoring <2.0 were considered low risk
  • Patients scoring 2.0 to 6.0 were considered moderate (intermediate) risk
  • Patients scoring >6.0 at high risk of pulmonary embolus

Patients with a score of <2 have a pre-test probability of a PE of less than 15%.

Wells score can also dichotomised to create only 2 risk categories. This revised Wells Score has been adopted by NICE in its 2012 Guideline. In this system:

  • Patients scoring 4 or less are low risk (or PE unlikely)
  • Patients scoring more than 4 are high risk (or PE likely)

The Revised Geneva Score / Simplified Revised Geneva Score

The Revised Geneva Score has the advantage of not relying on Gestalt clinical acumen as none of the parameters take this into account. It is widely used in Europe and has similar performance to Wells Scoring in the risk stratification of patients with possible PE.

Table 2: Revised and Simplified Revised Geneva Scores
Points
Variable Revised Geneva Simplified revised Geneva
Age >=65 year 1 1
Previous DVT/PE 3 1
Recent surgery/Fracture (<4/52) 2 1
Active malignancy 2 1
Unilateral lower limb pain 3 1
Haemoptysis 2 1
Pulse:
75 94 bpm 3 1
>=95 bpm 5 2
Pain on lower limb deep vein palpation
or unilateral oedema
4 1

In the Revised Geneva Score patients are divided into three risk groups:

  • Patients scoring 0 to 3 are considered low risk
  • Patients scoring 4 to 10 are considered moderate (intermediate) risk
  • Patients scoring 11 to 25 are at high risk of pulmonary embolus

Patients scoring 0 to 3 have a pre-test probability of a PE of approximately 8%.

In the Simplified Revised Geneva Score:

  • Patients scoring 0 to 2 are low risk (or PE unlikely)
  • Patients scoring 3 or more are high risk (or PE likely)

Patients scoring 0 to 2 have a pre-test probability of a PE of approximately 13%.

Pulmonary Embolus Rule-out Criteria (PERC)

A large US study reported that use of the PERC tool by a board certified emergency department clinician in the assessment of patients at low risk of PE allowed re-stratification of some patients into a no risk group where further investigation (including D-dimer) may not be needed11. A 2012 systematic review suggests that these patients have less than a 2% chance of having a PE12.

Table 3: Pulmonary Embolus Rule-out Criteria (PERC)
All answers to the following questions must be yes:
Low risk by Gestalt or other criteria?
Age <50?
Pulse <100?
Oxygen saturations on room air >94%?
No unilateral leg swelling?
No haemoptysis?
No recent trauma or surgery?
No previous VTE?
No oral hormone use?

The American College of Emergency Physicians13 has included the following level B recommendation in its 2018 clinical policy on acute venous thromboembolism.

Level B Recommendations

For patients who are at low risk for acute PE, use the Pulmonary Embolism Rule-out Criteria (PERC) to exclude the diagnosis without further diagnostic testing.

NICE guideline14 on the diagnosis of VTE suggest that in patients in whom the clinical suspicion of PE is low, ie; estimated to be less than 15% based on overall clinical impression, using PERC can be considered to help determine whether any further investigations are needed.

The use of PERC however is not included in their visual aid on the diagnostic work up of PE as the evidence to support is use is limited.

Nice suggest in low risk patients PERC may reduce the need for further testing and unnecessary anticoagulation.

Learning bite

The PERC tool may be useful for ruling out PE in a select cohort of patients, when used by experienced clinicians.

Risk Stratification and further investigations

Large studies [16] (e.g. PIOPED 1990) have suggested that even in patients risk-stratified as having a low probability of pulmonary embolus, PE is present in around 9% of cases. Further investigations are therefore required for patients in this group to reduce their risk of being discharged with a PE to an acceptable level.

D-Dimer

The most important, simple test, available to emergency physicians to exclude a diagnosis of PE is the D-Dimer test. D-Dimer is a sensitive but not specific investigation which gives rise to its poor positive predictive value. In addition to VTE it is also elevated in the setting of infection, trauma, cancer and inflammatory diseases15. D-Dimer should therefore only be used to exclude PE in those patients in whom a negative result will allow confident exclusion of the diagnosis (PE Unlikely) group. D-Dimer should NOT be used to exclude PE in patients in the high clinical probability (PE likely) group, as a negative result has not been shown to exclude the diagnosis in these patients7. These patients should go on to have definitive imaging tests instead.

A positive test is used to inform further diagnostic approaches rather than treatment decisions.

Types of D-dimer test

There are two basic types of D-dimer assay:

Qualitative bedside assays (e.g. SimpliRED, Simplify D-dimer)
Quantitative ELISA or Latex laboratory based assays (e.g. Vidas or MDA)

Most qualitative tests can only reliably exclude pulmonary embolus in patients with a low clinical probability of the disease16. Quantitative tests, on the other hand, have been shown to be highly sensitive in excluding the diagnosis of PE in patients at either low or intermediate clinical probability17.

In the UK, NICE has suggested using D-Dimer only for patients classified as PE unlikely (using dichotomised Wells Score) and an intermediate category of risk is not considered. NICE has evaluated evidence for both qualitative and quantitative assays and does not state a preference for either. However, it is important to be familiar with the type of assay available in your hospital, as different tests have varying sensitivities.

If carried out correctly, pulmonary embolus can be effectively excluded in those patients with a negative D-Dimer (A negative D-Dimer result will reduce the risk of PE to less than 1% if the pre-test probability is less than 20%) and no further imaging is required. It is important to ensure that an alternative diagnosis is sought to explain the patients symptoms.

Learning Bite

It is important to know which type of D-Dimer assay is used in your hospital.

Learning Bite

In low risk patients with negative investigation for PE it is important to ensure that an alternative diagnosis is sought to explain their symptoms.

Application of D-dimer testing

The results of D-Dimer testing should only be considered in the context of the clinical probability of PE derived from one of the clinical risk tools previously described.

Depending on the clinical situation and the results of these more simple tests, more complex tests may be required.

A diagnostic strategy for patients attending the ED with symptoms suggestive of pulmonary embolus has been published by NICE14 as part of wider guidance on the diagnosis and management of VTE. The most up to date version was published by NICE in 2020.

Radiological Investigations

Low risk patients with a positive D-Dimer and high risk patients require further imaging. Imaging techniques include the following:

  • CT pulmonary angiogram (CTPA)
  • V/Q scanning
  • Echocardiography (particularly in those too sick to be moved from the ED)
  • Leg vein ultrasound (limited applicability)

CTPA and V/Q scanning involve ionising radiation and the injection of contrast media exposing the patient to a level of risk.

(i) Computed Tomographic Pulmonary Angiography (CTPA)

CTPA is the investigation of choice due to its greater sensitivity and specificity for PE than V/Q scanning and its ability to identify alternate diagnoses. The sensitivity of CTPA is between 85-90% but its negative predictive value is high (96-97%) and therefore it can reliably exclude PE even in high risk groups18,19. Studies that have followed up patients sent home following negative CTPAs found favourable outcomes so it would seem that even if some PEs are missed these are likely to be small and unlikely to reoccur. CTPA can identify very small PEs in peripheral vessels below the 5th division of the pulmonary artery. There is some debate as to whether this size of thrombus may represent the normal turn-over of clot in the body which have been filtered out by the lung. At the moment however evidence that these small clots do not require treatment is lacking and for ethical reasons such evidence may not be forthcoming in the future.

In patients with a high pre-test probability for PE, CTPA may be falsely negative. Thus in patients with a high clinical suspicion of PE and a negative CTPA, additional imaging may be considered (e.g. D-Dimer, leg ultrasound, MRI, invasive pulmonary angiography)

CTPulmonarAngiogram

Fig 3: CT Pulmonary Angiogram showing massive filling defect (clot) in main pulmonary vessels

(i) Isotope lung scanning (V/Q scanning)

V/Q scanning can be used for patients with a normal chest radiograph and no chronic cardiopulmonary disease. It risk stratifies patients into low, intermediate and high probability of pulmonary embolism:

  • For low risk patients with a low probability V/Q scan a pulmonary embolism is considered to have been excluded
  • For high risk patients with high probability V/Q scan then a PE is considered to have been confirmed.

Unfortunately, isotope lung scanning rarely confirms the diagnosis of PE reliably and many patients with scans where the probabilities are intermediate and the risks uncertain leaving the clinician with difficult diagnostic decisions or the requirement for further tests. For this reason, isotope lung scanning has been largely replaced by CTPA in most patients.

perfusionscan
Fig 4: Perfusion scan showing multiple large defects typical of pulmonary embolism

(i) Echocardiography

Echocardiography can be useful in assisting with the diagnosis of PE especially in seriously ill patients that are too ill to be taken for a CT scan. With large PEs an echocardiogram may provide indirect evidence of the diagnosis revealing right ventricular strain and high PA pressures but only rarely will clot in the right side of the heart or pulmonary artery be seen21. The most common role for echocardiography in PE patients is to risk stratify patients with large PEs who are not haemodynamically unstable in order to help guide management.

(ii) Ultrasound

Leg vein ultrasound is useful for patients with clinical evidence of a DVT and identification of clot will preclude the need for advanced chest imaging (e.g. in pregnancy). However, a negative scan does not exclude sub clinical DVT and in one study a third of patients with negative leg ultrasound were subsequently found have a pulmonary embolus on angiography22.

Learning Bite

Leg ultrasound alone cannot reliably exclude venous thromboembolism in patients presenting with symptoms suggestive of pulmonary embolism5.

Patients with a negative CTPA, in whom there is ALSO a clinical suspicion of DVT should go on to have imaging of their leg veins.

Note: CTPA and V/Q scanning involve ionising radiation and the injection of contrast media exposing the patient to a level of risk.

Patients awaiting investigation

All patients in the PE likely subgroup and those in the PE unlikely subgroup who have a positive D-dimer need to receive anticoagulation (usually with low molecular weight heparin) whilst awaiting further investigation (e.g. via CTPA). Only if CTPA is immediately available can such anticoagulation be deferred until results are available.

Learning Bite

All PE likely patients and those in the PE unlikely subgroup who have a positive D-dimer, awaiting investigation need to receive anticoagulation

Stable Patients with Confirmed Pulmonary Embolism

Oxygen:

Oxygen should be administered to any patient with oxygen saturations of <94% on room air (BTS oxygen guidelines, 2008).

Anticoagulation:

All patients with confirmed PE require anticoagulation, but there is debate as to the length of time for which anticoagulation is required in pulmonary embolism.

  • There is no clear evidence that anticoagulating patients for 6 months is any more beneficial than doing so for 3 months, but the increased risk of bleeding may be important
  • NICE 2020 clinical guideline suggests that all patients should be offered anticoagulation for at least 3 months.
  • The decision to continue beyond 3 months needs to be evaluated based on the individuals risk of recurrences compared to risk of bleeding.
  • If there have been multiple episodes or continuing risk factors such as malignancy lifelong anticoagulation should be recommended.

With the increase in evidence supporting the use of DOACs (direct oral anti-coagulants) for the management of PE, most centres have moved away from using Vitamin K antagonists such as warfarin as first line for management of VTE.

NICE recommends the use of either apixaban or rivaroxaban as first line for patient and gives guidance on what agents to use if neither of these are possible in individual patients.

Always use local hospital guidelines when choosing an anticoagulation strategy.

Learning Bite

Fonduparinux, a newer alternative to LMWH, may be considered for certain religious groups (part of the production process of LMWH uses pigs) and patients who have had previous problems with heparin such as thrombocytopenia.

Unstable Patients with suspected or confirmed Pulmonary Embolism

Decision making around thrombolysis is complicated and should be approached in a multidisciplinary fashion by senior clinicians with relevant expertise. Many guidelines including the European Society of Cardiology guidelines24 suggest the use of a PERT model (pulmonary embolus response team model) to assess each individual patients risk factors for mortality from PE vs their risk from thrombolytic therapy.

Thrombolysis is indicated for patients with haemodynamic instability, ie: a systolic blood pressure <90mmHg or a drop in systolic of >40mmHg for >15 minutes not caused by another cause.

The decision to administer thrombolytics may be made by senior clinicians prior to confirmatory testing in patients who are peri-arrest and in whom the clinical suspicion for pulmonary embolism is sufficiently high and where emergency CTPA is not possible. In such cases point of care ultrasound may aid decision making.

For patients with sub-massive PE decision making surrounding the need for fibrinolytic therapy is more complex and should be made on a case-by-case basis. NICE15 states that thrombolytics should not be offered to haemodynamically stable patients with or without RV dysfunction.

Some clinicians advocate that intermediate-high risk patients with without haemodynamic instability may be considered for thrombolytic therapy. The PEITHO25 trial published in 2014 demonstrated reduced haemodynamic decompensation in intermediate risk patients but an increased risk of major haemorrhage or stroke. The HI-PEITHO26 trial is currently ongoing looking at the use of endovascular therapy vs anticoagulation alone in this patient group. Decision making around treatment approach in this patient cohort is discussed in detail in the ESC 2019 guideline for the diagnosis and management of acute PE24.

thrombolysis_guideline

Fig 5: American Heart Association Guideline on Thrombolysis for PE26

Outpatient (ambulatory) management

Traditionally patients with suspected or proven pulmonary embolism have been admitted to hospital and anticoagulated. However, it is now accepted that in young, fit patients with normal saturations, pulse rate and no signs of right heart strain outpatient investigation and anticoagulation is a safe alternative.

The Pulmonary Embolism Severity Index (PESI)27 and a simplified version of PESI28 have been used to decide which patients may be suitable for outpatient or ambulatory care. Some departments are now using such scores as the basis for ambulatory care pathways for patients with suspected PE. (PESI Score/Simplified PESI Score see Table). Thus, patients with a Simplified PESI Score of zero are considered at low enough risk to treat as outpatients. NICE guidelines15 suggest that outpatient treatment can be considered for low risk patients.

pesi

Pulmonary Embolus in Special circumstances

(i) Active Cancer:

There is evidence of an important reduction in recurrent VTE in cancer patients given LMWH compared to those given warfarin28. In addition, INR control is often more difficult in patients receiving chemotherapy.

There is increasing evidence to support the use of DOACs in patients with active cancer.

Decisions on choice of anticoagulant should be made in conjunction with the patients oncology team.

After 6 months, the decision to continue anticoagulation should be discussed with the patient in light of ongoing risks and benefits. Current recommendations suggest anticoagulation should be continued beyond 6 months if the malignancy is still present, unless there are contra-indications to anticoagulation. There are many nuances to both the decision to continue anticoagulation and the dose to provide. These decisions should be discussed with the patient by a person with expertise in the area.

(ii) Pregnancy:

Pregnancy, particularly late pregnancy is a significant risk factor (4 times relative risk) for the development of venous thromboembolism. D-Dimer levels are often elevated in pregnancy which limits its use as a triage tool. Although a negative D-Dimer in a low risk patient in early pregnancy may be considered helpful, use of D-Dimer to exclude PEs is not supported by the Royal College of Obstetricians and Gynaecologists.

Investigation strategies in pregnant patients frequently advocate bilateral leg vein ultrasonography initially in order to minimise ionising radiation exposure. The pick up rate for this investigation is very low however and a need to progress to further imaging is frequently required.

Although the total radiation doses with V/Q and CTPA are small, a CTPA gives a larger dose of radiation to maternal breast tissue than V/Q whereas V/Q gives a larger dose of radiation to the foetus. Women with suspected PE should be advised that V/Q scanning carries a slightly increased risk of childhood cancer compared with CTPA (1/280,000 versus less than 1/1,000,000) but carries a lower risk of maternal breast cancer (lifetime risk increased by up to 13.6% with CTPA, background risk of 1/200 for study population).

Some centres advocate a half dose perfusion scan as a first test although this can sometimes lead to a further test (CTPA) being needed if the scan is indeterminate resulting in the patient receiving a larger radiation dose overall..

Learning Bite

Emergency Medicine physicians should be able to explain the level of risk to mother and foetus of investigations that they may request from the ED since these questions are frequently asked.

Treatment of PE in Pregnancy

LMWH is the treatment of choice for PE in pregnancy. In pregnancy the pharmacokinetics of LMWH is altered and a twice daily regime is indicated. The dose of Enoxaparin is 1mg/kg b.d. in this situation. Unfractionated heparin is associated with osteoporosis and thrombocytopenia and is not recommended for prolonged use. Unfractionated heparin is reserved for cases of massive PE (where it may be used in combination with thrombolysis).

Oral anticoagulation is not given during pregnancy due to a greater bleeding risk and teratogenic risks to the developing foetus. A temporary IVC filter may be inserted prior to delivery as anticoagulation will need to be stopped due to the risk of haemorrhage. When VTE occurs in the antepartum period, delivery should be delayed, if possible, to allow maximum time for anticoagulation rather than putting in a filter.

Learning Bite

LMWH should be administered twice daily for patients with PE in pregnancy.

(i) Intravenous Drug Misusers:

Patients who use inject intravenous drugs, particularly those that inject into central veins, are at risk of deep vein thrombosis and subsequent PEs. The mechanism of formation of DVT in this group is probably related to repeated femoral vein puncture with injection of irritant substances, leading to endothelial damage and local release of tissue factor.

Intravenous drug misuse is a particular risk factor for DVT in some geographical areas. One study from Glasgow29 found that more than half of the DVTs diagnosed in women under the age of 40 years were caused by intravenous drug misuse. Robust data on the risk of developing pulmonary embolus as a result of intravenous drug abuse is lacking however. In the same Glasgow study none of the drug abusing patients with DVT subsequently developed clinical signs of pulmonary embolus. In another study, 3 of 47 injecting drug abusers with confirmed DVT (around 6%) developed a PE.

Pulmonary embolus in this group of patients is often associated with infection and septic pulmonary emboli were the most common pulmonary complication of drug misuse in one study. It should also be noted that foreign particle embolisation can occur with needles, talc, cotton and other non-soluble substances being reported in the literature. Such foreign particle embolisation can cause granuloma formation with subsequent deterioration in lung function.

Management of pulmonary embolus in intravenous drug addicts is often difficult due to their chaotic lifestyles. Oral anticoagulants are rarely prescribed due to the risk of non-compliance with medication or monitoring. Patients who continue to inject into large veins also present a persistent bleeding risk.

Most drug users are managed with low molecular weight heparin, usually for 3 to 6 months.

Consideration should be given to co administration of antibiotics given that PE in this group is often associated with sepsis.

  • The key to successful diagnosis or exclusion of pulmonary embolism in patients presenting to the emergency department is to consider the diagnosis in all patients with symptoms of dyspnoea, tachypnoea, chest pain, syncope or collapse (level 5 evidence)
  • Once the diagnosis has been considered, all patients should undergo a focussed clinical assessment in order to risk stratify their risk of PE (level 2 evidence)
  • Investigation readily available in the ED such as ECG, chest radiograph and arterial blood gas analysis cannot reliably exclude a diagnosis of pulmonary embolism (level 1 evidence)
  • Only patients at low clinical risk of PE (PE Unlikely) should undergo D-Dimer testing (level 1 evidence)
  • Patients with high clinical probability of PE (PE Likely) and those with a positive D-Dimer test should be treated with low molecular weight heparin prior to definitive imaging (level 5 evidence)
  • CTPA is the imaging modality of choice for non-pregnant patients (level 1 evidence)

Pitfalls

  • Failure to consider the diagnosis of PE in patients with symptoms such as unexplained breathlessness, syncope, postural hypotension or atypical chest pain.
  • Inappropriate use of the D-Dimer test to exclude PE in patients with high pre-test probability of pulmonary embolus.
  • Inappropriate use of the D-Dimer test to exclude PE in pregnancy
  • Considering a negative CTPA in a patient at high clinical risk of pulmonary embolism to rule out PE without considering additional investigation.
  • Considering absence of a DVT on ultrasound to rule out a PE
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