11: Pulmonary embolus, pulmonary hypertension, and vasculitides

CHAPTER 11
Pulmonary embolus, pulmonary hypertension, and vasculitides


Abbreviations



ABG
arterial blood gas
ABPA
allergic bronchopulmonary aspergillosis
ANCA
anti‐neutrophil cytoplasmic antibodies
APTT
activated partial thromboplastin time
AVM
arterio‐venous malformation
BMPR2
bone morphogenetic protein receptor 2
CO
carbon monoxide
COPD
chronic obstructive pulmonary disease
CPFE
combined pulmonary fibrosis and emphysema
CTEPH
chronic thromboembolic pulmonary hypertension
CTPA
computed tomography pulmonary angiogram
CUS
compressive lower extremity ultrasound
CXR
chest X‐ray
DVT
deep vein thrombosis
ECG
electrocardiogram
ECHO
echocardiogram
eGFR
estimated glomerular filtration rate
EGPA
eosinophilic granulomatosis with polyangiitis
ELISA
enzyme linked immunosorbent assay
GPA
granulomatosis with polyangiitis
Hb
haemoglobin
HDU
high dependency unit
HHT
hereditary haemorrhagic telangiectasia
HIT
heparin induced thrombocytopaenia
HIV
human immunodeficiency virus
HRCT
high‐resolution computed tomography
ICU
intensive care unit
ILD
interstitial lung disease
INR
International Normalised Ratio
IVC
inferior vena cava
JVP
jugular venous pressure
IVUFH
intravenous unfractionated heparin
KCO
transfer coefficient
kPA
kilopascals
LMWH
low molecular weight heparin
LTOT
long term oxygen therapy
MPA
microscopic polyangiitis
MPO
myeloperoxidase
MRPA
magnetic resonance pulmonary angiogram
NICE
National Institute for Health and Care Excellence
NYHA
New York Heart Association
OSA
obstructive sleep apnoea
PAH
pulmonary arterial hypertension
PAP
pulmonary artery pressure
PDGF
platelet derived growth factor
PE
pulmonary embolus
PESI
Pulmonary Embolism Severity Index
PGI2
prostaglandin
PHT
pulmonary hypertension
PPH
primary pulmonary hypertension
PPV
positive predictive value
PR3
proteinase 3
PVOD
pulmonary veno‐occlusive disease
SCUFH
subcutaneous unfractionated heparin
SLE
systemic lupus erythematosus
SSRI
selective serotonin reuptake inhibitors
TED
thromboembolic disease
TGF
transforming growth factor
TLCO
carbon monoxide transfer factor (diffusing capacity)
TTE
transthoracic echocardiogram
UFH
unfractionated heparin
UK
United Kingdom
VEGF
vascular endothelial growth factor
VQ
ventilation perfusion
VTE
venous thromboembolism
WHO
World Health Organisation

Introduction


Diseases of the pulmonary vasculature can present with symptoms of breathlessness, chest pain and haemoptysis. In some cases, these disorders can be life‐threatening. Some conditions, such as pulmonary emboli, are relatively common. Pulmonary vasculitides, which can present with pulmonary haemorrhage and life‐threatening haemoptysis, can involve other organs and are much rarer. Pulmonary embolism, pulmonary hypertension and some of the commoner pulmonary vasculitic conditions are discussed in this chapter.


Pulmonary embolism


A pulmonary embolus (PE) is caused by the obstruction of one, or both, of the pulmonary arteries or one of its branches by thrombus. Pulmonary arteries can also be blocked by air, fat or tumour cells, but these will not be discussed in this chapter.


Thromboembolic disease is a term used for the development of deep vein thrombosis (DVT) in the deep veins of the legs and pelvis which then break off and travel to the lungs, causing obstruction of the pulmonary vasculature. DVT and PE develop when there is venous stasis, endothelial damage, and hypercoagulability, described as Virchow’s Triad (Figure 11.1). Table 11.1 lists the risk factors for developing DVT and PE.

Diagram of Virchow’s triad displaying 3 overlapping circles labeled vessel, blood and flow with a bar labeled thrombosis in the middle.

Figure 11.1 Virchow’s triad.


Table 11.1 Risk factors for developing thromboembolic disease.




























Hypercoagulability Stasis Endothelial damage
Malignancy Immobility Previous DVT
Thrombophilia Obesity Thrombophlebitis
Pregnancy Pregnancy Lower limb trauma
Oral contraceptive pill Long haul flight
Sepsis Low cardiac output

It is estimated that there are 120 cases of PE/100 000 population with the incidence increasing to 500/100 000 in those aged over 75 years. PE is estimated to be responsible for 0.5% of all deaths in Europe, the majority of which occur in hospitals. It is estimated that 1% of patients admitted to hospital develop an acute pulmonary embolus (PE), which is responsible for 5% of all deaths in hospital. There is a higher incidence of PE in African Americans and the incidence is less common in Asians.


All patients admitted to hospital should have a careful assessment and documentation of their risk of developing thromboembolic disease. Patients who have had surgery and who are immobile are at a particularly high risk of developing venous thromboembolism (VTE) because of venous stasis. Pregnant women also have an increased risk because of their hypercoagulable state and the occlusion of the pelvic veins caused by the enlarging uterus. Acute pulmonary embolus is the leading cause of maternal deaths in the UK. Patients with inherited thrombotic disorders, such as Factor V Leiden and prothrombin gene mutations, who may have a family history of thromboembolic disease, are also at an increased risk of developing PE, as are those with malignancy.


Prophylaxis with a low dose of low molecular weight heparin (LMWH) is recommended for those who are at risk, unless they have a risk of bleeding. Most patients who are going to have elective surgery and those who are immobile should be prescribed LMWH. It should be continued for a period after discharge from hospital. Patients who are ambulant with no specific risk factors may not require LMWH prophylaxis. Thromboembolic disease (TED) stockings are also used to prevent the development of DVT. If LMWH is contraindicated, for example because of an increased risk of bleeding or renal failure, then intravenous unfractionated heparin (UFH) infusion, which has a shorter half‐life and can be reversed more quickly, can be considered. Patients who have had a stroke should be offered graded elastic compression stockings (TED stockings) and mechanical calf pumps. All patients should be encouraged to mobilise as early as possible.


Thromboprophylaxis is not required for most patients who are undertaking long journeys, including long‐haul flights. Travellers should be reminded to keep hydrated, mobilise frequently, and do calf exercises to prevent venous stasis. High risk patients may require LMWH prior to a flight that is more than 12 hours long.


Acute pulmonary embolus


An acute PE is a common, and sometimes fatal, form of venous thromboembolism which should be considered in anyone presenting with dyspnoea, pleuritic chest pain, haemoptysis, hypotension, or cardiac arrest. The severity of symptoms will depend on how much the pulmonary circulation is occluded and where the emboli are. The clinical presentation can be highly variable and often non‐specific.


Symptoms of a PE can occur acutely (within seconds or minutes), sub‐acutely (over days or weeks), or occur slowly over many months, resulting in chronic thromboembolic pulmonary hypertension (CTEPH), which is discussed later in this chapter.


Prompt diagnosis and treatment of PE will reduce morbidity and mortality. A comprehensive history should include ascertaining the risk factors for developing thromboembolic disease and the calculation of a probability score.


Box 11.1 lists the commonest symptoms of a pulmonary embolus as determined in the Prospective Investigation of Pulmonary Embolism Diagnosis 11 (PIOPED 11) Study.


Patients usually develop sudden onset of breathlessness within minutes, especially if the thrombus blocks the main or lobar pulmonary vessels. However, patients may experience very mild symptoms or be asymptomatic, even with a large PE, and present after a delay of days or weeks. In a systematic review of studies, one‐third of patients with DVT were found to have an asymptomatic PE.


Pleuritic chest pain is more likely to develop with smaller, more peripheral emboli, which result in inflammation of the visceral pleural membrane. This can lead to pulmonary infarction in 10% of cases, resulting in haemoptysis.


The differential diagnoses for anyone presenting with pleuritic chest pain and dyspnoea includes a variety of common respiratory conditions, such as acute asthma, pneumothorax, exacerbation of COPD, community acquired pneumonia, and heart failure.


The clinical signs of pulmonary embolus are relatively non‐specific and include tachypnoea and a pleural rub if the patient presents late and has developed pulmonary infarction. Oxygen saturation measurement at rest may appear normal if the embolus is small, but a desaturation of more than 4% on exertion should alert the clinician to the possibility of a PE. PE should be suspected when there is hypotension and the JVP is elevated. If pulmonary embolus is suspected, then the lower limbs should be examined for evidence of a DVT which presents with leg swelling and pain on palpation. Box 11.2 lists the frequency of the common presenting signs on clinical examination.


A large saddle embolus, which lodges at the bifurcation of the main pulmonary artery and extends into the right and left main pulmonary arteries, occurs in 3–6% of cases and carries a mortality of 5%. These emboli can move distally and lodge in the segmental or sub‐segmental branches.


Diagnosis of pulmonary embolus


It is recommended by NICE that a pre‐test clinical probability score should be calculated in all patients with a suspected PE. In combination with simple investigations, this score can be used to decide whether further investigations are required. This is important as this avoids unnecessary investigations, such as a computed tomography pulmonary angiogram (CTPA), which exposes the patient to a high dose of radiation. However, it is important that a patient with risk factors for PE has appropriate investigations so that a PE is not missed.


The NICE guidelines recommend the use of a two‐level modified Wells score (Table 11.2) to assess the probability of an individual patient having a PE. A score greater than 4 indicates that a PE is likely and a score less than 4 suggests that a PE is unlikely. The Geneva score is an alternative score that is sometimes used.


Table 11.2 Modified Wells score.




























Clinical feature Points
Clinical symptoms of DVT 3
Other diagnosis less likely than PE 3
Heart rate > 100 bpm 1.5
Immobilisation or surgery within last 4 weeks 1.5
Previous DVT or PE 1.5
Haemoptysis 1
Malignancy 1

Score 2 or less: Low risk of PE.


Score 2–4: Intermediate risk of PE.


Score > 6: High risk of PE.


Investigations in the diagnosis of pulmonary embolus


Most of the routine investigations that a patient will have when presenting to hospital are non‐specific and therefore not useful on their own in making or excluding a diagnosis of PE.


The ECG is often normal. The commonest ECG abnormality is sinus tachycardia. Other ECG changes, which occur in 70% of patients with a PE, include right heart strain, right axis deviation, depression of the ST segment, and T wave inversion in leads V1–V3. The S1Q3T3 pattern occurs in less than 10% of patients (Figure 11.2). Patients who develop bradycardia, atrial arrhythmias, new right bundle branch block, inferior Q‐waves, and anterior ST‐segment changes have a worse prognosis.

Image described by caption and surrounding text.

Figure 11.2 ECG changes seen in pulmonary embolus.


The chest X‐ray (CXR) is normal in approximately 20%, and is an essential investigation to exclude pneumothorax, consolidation, and cardiac failure. A small pleural effusion is found in 47% of patients with a PE; this is often blood‐stained if aspirated. Other radiological changes include atelectasis, pruning of the pulmonary vasculature with distal hypoperfusion, and a wedge‐shaped opacity in the lung periphery (Figure 11.3).

Image described by caption and surrounding text.

Figure 11.3 CXR showing right lower lobe infarction after a pulmonary embolism.


Arterial blood gas (ABG) analysis is not a sensitive or specific test in the diagnosis of PE, but 74% of patients will be hypoxic. Approximately 41% will have hypocapnia and a respiratory alkalosis. PE should be considered in anyone who has a normal CXR and unexplained hypoxaemia. Ventilation perfusion mismatch will result in widening of the Alveolar‐arterial (A‐a)gradient in the majority. The calculation of the A‐a gradient is described in Chapter 13. Although not helpful on its own to make a diagnosis, the ABG at presentation may be of prognostic value. As patients with an initial oxygen saturation of less than 95% have an increased risk of respiratory failure and death, it is recommended that such patients are admitted to hospital for careful monitoring while undergoing investigations and treatment.


D‐dimer is a breakdown product of cross‐linked fibrin and levels will be elevated in patients with thromboembolism. Sensitive D‐dimer testing using ELISA (enzyme‐linked immunosorbent assay) is recommended. Although it is a sensitive test, with a greater increase in those with larger PEs, it lacks specificity. D‐dimer levels will be elevated in those with any acute illness and in pregnant women. D‐dimer levels will be falsely positive in patients with chronic renal failure with an estimated glomerular filtration rate (eGFR) <60 ml min−1/1.73 m2. The D‐dimer level also increases gradually in patients over the age of 50 years. Age‐adjusted D‐dimer values may increase the specificity of the test, but this is not routinely done in the UK.


The D‐dimer level is only useful in excluding a PE and should not be used to make a diagnosis of PE. According to the NICE guidelines, the D‐dimer should be used in conjunction with the modified Wells score to determine the need for further investigations. If the modified Wells score is greater than or equal to 4, then the patient should go on to have further investigations to confirm the diagnosis of PE, regardless of the D‐dimer level. In those with a high clinical suspicion of PE and a normal D‐dimer level, the prevalence of PE is 20–28%.


If the probability of PE is considered unlikely (modified Wells score of less than 4), then a D‐dimer level should be obtained. If this is negative, then no further testing is required. In those in whom the D‐dimer level is elevated, a CTPA is required.


Although not sensitive or specific, serum Troponin I and T levels may indicate right ventricular dysfunction. Raised levels may be elevated in 30–50% of patients with a large PE and may be of prognostic value. The levels are rarely as high as would be after a myocardial infarction and return to normal within 2 days.


Imaging to confirm a diagnosis of PE


Computed tomography pulmonary angiogram (CTPA)


CTPA with intravenous contrast is a rapid test that is available in all hospitals in the UK. CTPA is the imaging of choice in a non‐pregnant patient with normal renal function who is haemodynamically stable and not allergic to contrast. CTPA may not be the optimal investigation in the morbidly obese patient and in women under the age of 40 because of the high dose of radiation to the breasts, which may increase the risk of breast cancer.


An algorithmic approach which combines CTPA with clinical assessment and D‐dimer levels increases the sensitivity and specificity of the test. CTPA has a sensitivity of over 90% for the diagnosis of PE, which increases to 96% when combined with a clinical probability assessment. The specificity of CTPA is 95%. When the modified Wells score is <2, the positive predictive value (PPV) of CTPA is 58%. If the Wells score is 2–6, then the PPV is 92% and for a Wells score >6, the PPV rises to 96%.


A PE will appear as a filling defect in a branch of the pulmonary artery which is otherwise filled with contrast (Figure 11.4). CTPA is most accurate for the detection of a large PE blocking the main, lobar, and segmental pulmonary arteries. It is less accurate for detecting smaller, peripheral, sub‐segmental PEs. The modern multi‐detector scanners can detect smaller, more peripheral emboli. The CTPA also has the advantage of finding other abnormalities which may be responsible for the clinical symptoms and signs.

Image described by caption and surrounding text.

Figure 11.4 CTPA showing bilateral filling defects seen with multiple pulmonary emboli.


A positive CTPA will confirm a diagnosis of PE and a negative CTPA means that a PE is unlikely. When the clinical suspicion is high but the CTPA is negative, 5% will have a PE. Therefore, patients with a high Wells score and a negative CTPA may require further investigations, which may include a VQ scan or a contrast‐enhanced pulmonary angiogram.


Ventilation perfusion scan (VQ scan)


A VQ scan should be considered in any patient in whom a CTPA is contraindicated as discussed above. It should also be considered in women under the age of 40. A normal CXR is necessary when interpreting the VQ images and is, therefore, not a suitable investigation in a patient with chronic lung disease. A VQ scan may occasionally be indicated if the clinical suspicion of a PE is high but the CTPA is negative. A VQ scan is a nuclear medicine scan that is not available in all centres and not available out of hours because radioactive isotopes are required.


The PIOPED 11 study is the largest study to date which looked at the sensitivity and specificity of VQ scanning. A VQ scan has a moderately high sensitivity but a poor specificity, with a high number of false positive test results. As with CTPA, diagnostic accuracy was greater when the results of the VQ scan was combined with a clinical probability score.


A VQ scan is reported according to whether there are areas which have normal ventilation but abnormal perfusion (VQ mismatch). Patients with underlying lung disease, for example, COPD, will have matched ventilation and perfusion defects. A VQ scan can be reported as normal, low‐probability of PE, intermediate probability of PE, or high‐probability of PE.


A normal VQ scan means that a PE is unlikely, and no further investigations are required. A patient with a Wells score <2 and a normal or low‐probability VQ scan will have <4% chance of having a PE. If this is combined with a normal D‐dimer level, then the chance of a PE is <3%. A high probability VQ scan in a patient with a high clinical probability score means that there is a 96% chance of a PE (Figure 11.5). Patients with a low probability or inconclusive VQ scan will need further investigations (Figure 11.6).

Image described by caption and surrounding text.

Figure 11.5 : Ventilation perfusion scan showing perfusion defects in pulmonary emboli.

Image described by caption.

Figure 11.6 Ventilation perfusion scan showing VQ mismatch.


Patients with a high clinical suspicion of PE in whom a CTPA is either negative or contra‐indicated and in whom the VQ scan is inconclusive will require further imaging.


A contrast‐enhanced pulmonary angiogram is historically the definitive test for diagnosing PE and has a good sensitivity and specificity. Although it is an invasive test and is associated with a small risk of harm, it is safe and well tolerated in haemodynamically stable patients with <2% mortality. Complications include catheter‐related events, contrast‐related complications, and cardiac complications. One advantage of this test is that if a clot is directly visualised, it can be lysed by embolectomy and/or thrombolysis if anticoagulation is contra‐indicated.


A magnetic resonance pulmonary angiogram (MRPA) is less sensitive and specific and is rarely used. Proximal vein compressive lower‐extremity ultrasound (CUS) can detect a DVT so can indirectly make a diagnosis of PE. It is not recommended in routine practice for diagnosing PE as only 9–12% of patients with PE are found to have a DVT by this method. However, in those in whom other investigations are contra‐indicated, serial CUS done weekly for several weeks could be useful to detect DVT if the clinical suspicion is high. It is a valuable test in pregnant women as there is no exposure to radiation.


A transthoracic echocardiogram cannot make a diagnosis of PE, but in 30–40% of patients with a PE there will be changes consistent with right ventricular strain, which includes regional wall motion abnormalities that spare the right ventricular apex. In severe PE, there may be evidence of elevated right ventricular pressures, an increase in right ventricular size, tricuspid regurgitation, and pulmonary hypertension. In 4% of cases, a thrombus may be seen in the right ventricle, which confers a poor prognosis. The echo changes may be of prognostic value and resolution of changes can be used to monitor improvement with anticoagulation and, sometimes, to guide the length of anticoagulation. An echocardiogram can also diagnose other causes of hypotension and cardiovascular collapse, including aortic dissection and pericardial tamponade.


PE is a leading cause of mortality during pregnancy and in the 6 weeks post‐partum, accounting for 20–30% of maternal deaths. It is difficult for the clinician to calculate the clinical probability of a pregnant woman having a PE as there are no validated scores in this group of patients. The imaging to use in a pregnant woman often causes much concern for the doctor and the patient. All pregnant women who present with possible PE should have a CXR (with lead protection for the foetus) which may suggest an alternative diagnosis. Both CTPA and VQ scan will expose the foetus to some radiation. CTPA exposes the mother’s breasts to a significant dose of radiation at a time when they are particularly metabolic, thus increasing the future risk of breast malignancy. It is recommended that a CUS of legs and pelvis is a useful initial investigation in a pregnant woman if PE is suspected. If this is normal but the presentation is suggestive of a PE, then a half‐dose perfusion scan is recommended. CTPA is reserved for pregnant women who are clinically unwell and in whom other investigations are indeterminate.


Management of acute pulmonary embolus


Patients with suspected PE should receive oxygen and analgesia as required. Those with a high probability of PE (Wells score > 6) should receive LMWH while they are having investigations. Those with a moderate clinical probability (Wells score of 2–6) should be anticoagulated if the diagnosis is going to take more than 4 hours. It is recommended that all the diagnostic tests should be done within 4 hours. Patients with a low risk of PE should undergo investigations within 24 hours and do not require anticoagulation while waiting for the results.


Anticoagulation


Anticoagulation is the main treatment for PE. The risk of PE recurrence is 25% in patients with a high probability score and anticoagulation has been shown to reduce this. The main complication of anticoagulation is bleeding, and intracranial bleeding may be life‐threatening. The risk of bleeding is estimated to be 1.6% in the first 3 months in those with no risk factors for bleeding and will be up to 3% in those with risk factors. Minor haemoptysis, epistaxis, and menstruation are not contraindications to anticoagulation. Anticoagulation has also been shown to reduce mortality, the benefits outweighing the risk of major bleeding.


The aim of anticoagulation is to reach a therapeutic level within 24 hours of treatment using either LMWH, subcutaneous fondaparinux, intravenous unfractionated heparin (IVUFH), or subcutaneous unfractionated heparin (SCUFH). A patient diagnosed with PE with a high risk of haemorrhage should be discussed with an expert prior to anticoagulation.


LMWH is recommended in haemodynamically stable patients with normal renal function. It is not indicated in patients who are morbidly obese as there is decreased absorption of medication given subcutaneously. Advantages of LMWH over IVUFH include lower mortality, fewer recurrent thromboembolic events, fewer major bleeding episodes, and a lower incidence of heparin induced thrombocytopaenia (HIT). LMWH has more predictable pharmacokinetics than UFH, requires twice daily administration of a fixed dose, and monitoring of anti‐Xa levels is not required. The choice of which LMWH to use will be dictated by the cost and clinical experience. The dose is calculated according to the patient’s weight and given subcutaneously by injection.


LMWH is also recommended for the treatment of PE in a pregnant woman and more careful monitoring is recommended. Anticoagulation should be continued for 3 months after birth if pregnancy is the only risk factor for developing the PE. Those with other risk factors may need a longer period of anticoagulation. Warfarin is teratogenic so is contraindicated in pregnancy, particularly in the first trimester. Warfarin is, however, considered to be safe in breastfeeding mothers.


IVUFH is recommended in patients with massive PE and hypotension as they may require thrombolysis and the effects of the UFH can be reversed with protamine sulphate more rapidly than when patients receive LMWH or fondaparinux. IVUFH is also indicated in those in whom there is an increased risk of bleeding, those with renal failure (creatinine clearance less than 30 ml min−1) and in the morbidly obese. Patients on UFH will require monitoring of their activated partial thromboplastin time (APTT).


Oral anticoagulation


Warfarin, a vitamin K antagonist, which blocks the production of the vitamin‐K dependent clotting factors (11, V11, 1X and X), is the drug most commonly used for the long term treatment of PE. It is effective in preventing recurrent PEs and DVTs. Warfarin can be started as soon as the diagnosis of PE is confirmed while the patient is on the treatment dose of LMWH but should not be started without prior treatment with LMWH as there is evidence that this may increase the incidence of PE and/or DVT. It is recommended that LMWH treatment should continue for at least 5 days after starting treatment and until the International Normalised Ratio (INR) has been therapeutic (between 2 and 3) for at least 24 hours. This is because it takes at least 5 days for the intrinsic clotting pathway activity to be suppressed. It is recommended that the starting dose of warfarin should be 5 mg for 2 days and then the dose calculated according to the INR. The effects of warfarin can be reversed by giving vitamin K. Fresh frozen plasma can also be given if necessary.


Warfarin is a cheap drug but has a narrow therapeutic range and requires monitoring. Warfarin is a drug that has interactions with other commonly used drugs which are metabolised through the cytochrome P450 system. Doctors should be aware of these interactions. Certain food items, particularly those containing vitamin K, can also alter warfarin levels, so patients should be given information booklets with details of foods to avoid.


Increasingly, Factor Xa inhibitors, such as rivoroxaban, apixaban, and edoxaban are being used. Dabigatran, a direct thrombin inhibitor, is also being used in certain circumstances. These are fixed dose agents that do not require monitoring. However, the effects cannot be easily reversed. It is not within the scope of this book to discuss these newer anticoagulants in detail.


Patients with PE who are haemodynamically stable, not hypoxaemic, not in respiratory distress, who do not have significant co‐morbidities, no increased risk of bleeding, and who do not live alone can be safely anticoagulated at home.


Duration of anticoagulation


The length of time that anticoagulation should be continued depends on the underlying cause of the PE. Rates of clot resolution with anticoagulant therapy are variable. It is estimated that there is resolution of the PE in 40% of patients within 1 week, in 50% within 2 weeks and in 73% within 4 weeks. Thrombi can also move during anticoagulation.


If the DVT and/or PE is due to an identifiable risk factor, such as immobility or surgery, the guidelines recommend 3 months of anticoagulation, so long as the INR is therapeutic during this period. The patient should be reviewed after this period to ensure that the symptoms have resolved and that there is no evidence of pulmonary hypertension.


Patients who have an ongoing risk of thromboembolism, such as an inherited clotting disorder, will require lifelong anticoagulation. Patients with an unprovoked PE, with no obvious risk factors, should have a thorough clinical assessment and appropriate investigations to exclude malignancy. They may require life‐long anticoagulation as the risk of recurrence is 25% at 5 years without anticoagulation. The risk of bleeding is estimated to be 1.2% at 5 years. The risk of PE recurrence if anticoagulation is stopped, together with the risk of bleeding with continuing anticoagulation, should be discussed.


Patients with malignancy have an increased risk of PE. LMWH is recommended for patients with malignancy who develop PE. These patients also have an increased risk of bleeding, so the decision as to which anticoagulation to use, and for how long, must be made after weighing up the pros and cons for each patient.


Inferior vena cava filter


An IVC filter should be considered in anyone with a diagnosis of PE who has a significant risk of haemorrhage if commenced on anticoagulation. This includes those who are more than 65 years old, those with recent surgery, known haematological risk factors, liver failure, and malignancy. Patients who have extensive DVT and pelvic malignancy may also have recurrent episodes of PE as the clot breaks off and travels to the lungs. Retrievable filters are recommended, and the majority are placed infra‐renally to prevent further emboli from reaching the lungs. This is usually a temporary solution and the filter will need to be removed once anticoagulation has been optimised.


Management of massive life‐threatening pulmonary embolus


Approximately 8% of patients with a PE present with shock and collapse. Patients who have a systolic blood pressure of less than 90 mmHg may not be well enough for a CTPA to confirm the diagnosis but must rely on a bedside transthoracic echocardiogram which will show signs of right heart strain. Patients who present with a suspected massive pulmonary embolus with haemodynamic compromise, signs of right heart strain on transthoracic echocardiogram and or bilateral or saddle embolus on CTPA should be thrombolysed.


Patients should have immediate, but careful, intravenous fluid resuscitation, oxygen therapy to maintain the oxygen saturation between 94% and 98% and vasopressor support. If the intravenous fluid is given too aggressively, there is a risk of right ventricular failure. While waiting for confirmation of a PE, the patient should be commenced on IVUFH. Patients should receive 50 mg of alteplase as a bolus via a peripheral vein followed by intravenous heparin infusion. The activated partial thromboplastin time (APTT) should be maintained at between 1.5–2.5 times normal. Analgesia will be required for pain. Oral anticoagulation, usually with warfarin, should be started with a loading dose of 10 mg, with an aim to maintain the INR between 2 and 3.


Thrombolysis can increase the risk of cerebral and pulmonary haemorrhage. The decision to thrombolyse should be made by a senior respiratory physician after consultation with a radiologist and intensivists. Such patients should be managed in a high dependency unit (HDU) or intensive care unit (ICU).


If thrombolysis is contra‐indicated, for example, in a pregnant patient, or it fails, then catheter‐directed embolectomy or surgical embolectomy should be considered. These procedures are only available in tertiary centres and are associated with a high mortality.


Prognosis after acute PE


The overall mortality without treatment is 30% but reduces to 2–11% with anticoagulation. The risk of death is highest in the first week due to cardiogenic shock. The risk of recurrent PE is also greatest in the first 2 weeks. In the longer term, mortality is due to the underlying condition that caused the PE, such a malignancy.


The Pulmonary Embolism Severity Index (PESI) can be used to calculate the risk of death. Poor prognostic factors include age more than 65 years, co‐morbid conditions, shock, right ventricular failure, hypoxaemia, thrombus in the right ventricle, elevated brain natriuretic peptide and N‐terminal pro‐brain natriuretic peptide, and elevated troponin I and T levels.


Recurrent pulmonary emboli


Patients with recurrent, acute PE may require life‐long anticoagulation. Compliance with treatment should be checked, ensuring that the INR is therapeutic. Some patients, especially those with malignancy or pelvic DVTs, may have recurrent pulmonary emboli despite anticoagulation. In some patients it can be difficult to maintain the INR in the therapeutic range. In these patients, and those in whom anticoagulation is contra‐indicated, an inferior vena cava filter should be considered. If a patient with a known diagnosis of PE, who is already being anticoagulated, presents with symptoms and signs of a PE, the same diagnostic approach should be taken. Images should be carefully reviewed by the radiologist as interpretation may be difficult.


Chronic pulmonary emboli


Patients with chronic pulmonary emboli will present with progressively worsening breathlessness and clinical features of pulmonary hypertension, which includes raised JVP, peripheral oedema, and parasternal heave. The ECG may show right ventricular hypertrophy and right axis deviation. The CXR will show prominent pulmonary arteries. A VQ scan will demonstrate unmatched defects. These patients are at risk of developing chronic thromboembolic pulmonary hypertension (CTEPH), which will be discussed in the next section.


Pulmonary hypertension


Pulmonary vascular tone is dependent on the balance of vasoconstrictors and vasodilators. Oxygen is a potent vasodilator, therefore hypoxia results in vasoconstriction.


Pulmonary hypertension presents with insidious onset of breathlessness, fatigue, and pre‐syncope (Figure 11.7). When severe, patients can also experience atypical chest pains, peripheral oedema, palpitations, and syncope. Pulmonary hypertension can be due to a variety of different aetiologies as described in the WHO classification in Table 11.3. The NYHA Functional Classification (Box 11.3) is used to describe the severity of the dyspnoea.

Illustration of regulation of pulmonary vascular tone depicted by a triangle with a horizontal bar on top having two boxes for vasodilatation (left) and vasoconstriction (right). The boxes have texts inside.

Figure 11.7 Regulation of pulmonary vascular tone.


Table 11.3 WHO classification of pulmonary hypertension.




























Type Aetiology Management
Group 1: Pulmonary arterial hypertension Familial
Appetite suppressants
Prostacyclin
Endothelin receptor antagonist
Phosphodiesterase‐5 inhibitor
Group 2: Left heart disease: elevated left atrial pressure and pulmonary venous hypertension Congenital cardiomyopathies
Valvular heart disease
Outflow tract obstruction
Left ventricular systolic dysfunction
Left ventricular diastolic dysfunction
Management of underlying condition
Anticoagulation
LTOT
Group 3: Severe lung disease All causes of hypoxaemia, including COPD, ILD, sleep disordered breathing, alveolar hypotension Management of underlying condition
Anticoagulation
LTOT
Group 4: Thromboembolic disease (CTEPH) Develops secondary to chronic occlusion of proximal or distal pulmonary vessels Thromboendarterectomy
Group 5: Multifactorial Sickle cell disease
β‐thalassaemia
Spherocytosis
Myeloproliferative disorders
Sarcoidosis
Glycogen storage disease
Chronic kidney disease
Management of underlying condition
Anticoagulation
LTOT
Jun 4, 2019 | Posted by in RESPIRATORY | Comments Off on 11: Pulmonary embolus, pulmonary hypertension, and vasculitides
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