pulmonary embolism



OVERVIEW

Definition

A general term for a group of diseases or clinical syndromes whose pathogenesis is characterized by obstruction of the pulmonary arteries or their branches by various emboli.

Among them, pulmonary thromboembolism is the most common type of pulmonary embolism, and this article focuses on pulmonary thromboembolism.

The thrombus that causes pulmonary thromboembolism mainly originates from deep vein thrombosis in the lower extremities. Pulmonary thromboembolism and deep vein thrombosis are collectively known as venous thromboembolism, and both have the same susceptibility factors.

Types

Types according to the cause of the disease

Pulmonary thromboembolism, the most common.

Fat embolism syndrome.

Amniotic fluid embolism.

Air embolism.

Caused by other emboli.

Clinical staging of pulmonary thromboembolism

Acute pulmonary thromboembolism

Chronic thromboembolic pulmonary hypertension

Morbidity

Pulmonary thromboembolism and deep vein thrombosis have a high incidence worldwide and are closely related.

In China, the number of diagnosed cases of venous thromboembolism has increased rapidly in recent years, and the number of diagnosed cases of venous thromboembolism in the majority of hospitals has increased 10-30 times compared with that of 20 years ago.

Pulmonary thromboembolism has a high mortality and disability rate. With the improvement of domestic awareness and diagnosis and treatment of the disease, the hospitalization death rate of acute pulmonary thromboembolism patients in China decreased from 25.1% in 1997 to 8.7% in 2008.

Causes

Causes

The thrombus causing pulmonary thromboembolism mainly originates from deep vein thrombosis in the lower limbs. Tumor embolism caused by tumor, heart redundancy, bacterial embolism, fat embolism, gas embolism, amniotic fluid, and intravascular foreign bodies may all lead to pulmonary embolism.

After the embolus embolizes the pulmonary artery, the embolus is insoluble, mechanized, and the pulmonary vascular remodeling causes vascular stenosis or occlusion, which leads to the increase of pulmonary vascular resistance and the progressive increase of pulmonary artery pressure, and ultimately it can cause the right ventricular hypertrophy and the right heart failure, and the serious cases may lead to death.

Risk factors

Any factor that can lead to venous stagnation, endothelial damage and hypercoagulability is a high risk factor for pulmonary thromboembolism, which can be categorized into hereditary and non-hereditary factors:

Hereditary factors

Caused by genetic variation, patients are often repeatedly diagnosed with arterial and venous thrombosis.

Patients younger than 50 years of age who have recurrent arterial or venous thrombosis without obvious triggers or who have relatives with related manifestations need to be vigilant.

Non-genetic factors

Tumor: malignant tumor is one of the important high-risk factors for pulmonary embolism, and the risk varies with different types of tumors. Pancreatic, cranial, pulmonary, ovarian and hematologic malignant tumors are at higher risk, and the risk increases during the active stage of malignant tumors.

Age: The incidence of venous thromboembolism gradually increases with age, and the incidence of pulmonary thromboembolism increases as well, roughly doubling every 10 years for patients over 40 years of age.

Others: Pulmonary thromboembolism shares risk factors with certain arterial diseases, especially atherosclerosis, such as smoking, obesity, hypercholesterolemia, and hypertensive diabetes. Surgery, trauma, acute medical illnesses (e.g., heart failure, myocardial infarction, respiratory failure, infections, etc.), and certain chronic diseases (e.g., antiphospholipid syndrome, nephrotic syndrome, inflammatory bowel disease, and myeloproliferative disorders, etc.) are high risk factors.

Pathogenesis

Thrombus in the pulmonary artery endothelial attachment, the first volume atrophy, blood flow impact thrombus in the loose part, part of the small size of the embolus in about 2 weeks of autolytic disappearance.

The thrombus that cannot be dissolved, fibrin then covers its surface, and then endothelial cells also begin to cover, local pulmonary artery wall myocardium edema, thrombus attached to the endothelial surface of the artery neutrophil infiltration, arterial elastic fibers are destroyed.

The thrombus adheres to the arterial intima, and endothelial cells extend into the thrombus. 1 week later, granulation tissue appears in the thrombus and undergoes mechanization.

In the process of chronicity, the pulmonary artery will undergo intimal atherosclerosis, and in severe cases, there is focal fibrinoid necrosis or vitreous degeneration of the pulmonary artery wall.

Symptoms

Main manifestations

The clinical manifestations of pulmonary embolism are varied, all lack specificity and are easily overlooked. The classic “triad” of pulmonary embolism is dyspnea, chest pain, and hemoptysis, which occurs in less than 30% of patients.

Dyspnea and shortness of breath are the most common and primary symptoms, and the degree is related to the extent of the embolism.

Chest pain, mostly mild to moderate, is less extensive.

Cough or hemoptysis, which occurs in less than 30% of cases, and bleeding is usually small.

Syncope, which can be the only first symptom, tends to present as a transient loss of consciousness. If the syncope is caused by shock, it generally suggests a poor prognosis, and sudden death can occur in some patients.

Other manifestations

Palpitations, self-consciousness of heart beating discomfort.

Dizziness.

Restlessness, panic and sense of near death.

Sit-up breathing, with increased dyspnea, coughing and shortness of breath in the prone position, relieved by sitting up.

Profuse sweating, cold and clammy extremities.

Lower extremity pain or swelling: mostly a manifestation of combined lower extremity deep vein thrombosis.

Complications

Shock: may be characterized by a sense of near death, cold and clammy extremities, and a drop in blood pressure, which is often life-threatening.

Pulmonary atelectasis: may manifest as chest tightness, shortness of breath, fever and so on.

Pulmonary infarction: necrosis occurs when lung tissue lacks blood supply, which may manifest as shortness of breath, dyspnea, tachycardia, fever, chest pain, cough and hemoptysis.

Angina pectoris: increased myocardial oxygen consumption can lead to myocardial ischemia, inducing angina pectoris. Chest pain is the most dominant symptom, and the location of the pain includes the upper chest, the posterior sternum, and the abdomen. The pain can radiate to the neck, the angle of the jaw, and the teeth, as well as to the upper limbs, the left shoulder, and the interscapular region.

Cardiac arrhythmia: it may manifest as palpitations, shortness of breath, chest pain, dizziness or fainting.

Lung infection: it can present with fever, cough, sputum, chest tightness and other symptoms.

Pulmonary hypertension: mainly thromboembolic pulmonary hypertension, which may manifest as dyspnea, fatigue, decreased exercise tolerance, or even lead to right heart failure (generalized edema, fatigue, fatigue, etc.).

Consultation

Department of Medicine

Emergency Department

When sudden onset of chest pain, dyspnea, hemoptysis, dizziness or fainting occurs, it is recommended to consult the Emergency Department immediately.

Respiratory Medicine

For long-term follow-up after treatment of pulmonary embolism, respiratory medicine is recommended.

Preparation

Consultation: Registration, Preparation of documents, Frequently asked questions

Tips for medical consultation

Chest X-ray or chest CT is often needed during the consultation, so avoid wearing clothing made of metal, and those who are pregnant or planning to become pregnant should inform the doctor in time.

Preparation Checklist

Pay particular attention to the time of onset of symptoms and special manifestations.

Is there a cough, shortness of breath?

Is there breathlessness or dyspnea?

Is there chest pain?

Do you feel panicky?

How long have the symptoms been present?

Under what circumstances do the symptoms worsen or lessen?

Is there a malignant tumor?

Have you had recent surgery or trauma?

Has there been a venous thrombosis?

Is there long-term estrogen therapy, or oral contraceptives?

Test results in the last six months, which can be brought to the doctor’s office

Laboratory tests: blood count, D-dimer, arterial blood gas analysis

Imaging tests: chest X-ray, CT pulmonary arteriography, radionuclide pulmonary ventilation/perfusion (V/Q) imaging, magnetic resonance imaging (MRI), echocardiography

Medication use in the last 3 months, if available in boxes or packages, bring with you to the doctor’s appointment

Anticoagulants: low molecular heparin, warfarin, rivaroxaban

Others: estradiol, hexestrol, ethinyl estradiol, cotrimoxazole tablets

Diagnosis

Diagnosis is based on

Medical history

Most patients have a history of sedentary lifestyle, prolonged bed rest, history of trauma or surgery, history of malignant tumors, estrogenic drugs (in women), and history of venous thrombosis.

Clinical manifestations

Symptoms: dyspnea, chest pain, hemoptysis, cough, syncope, profuse sweating, irritability, cold and wet extremities, etc.

Signs: purplish skin on lips, fever (mostly low-grade), decreased blood pressure, rales or fine wet rales in lungs, tachycardia, hypertonic or split second tone in the pulmonary valve area, systolic murmur in the tricuspid valve area, and swelling of the affected limbs (in patients with deep vein thrombosis).

Laboratory tests

Plasma D-dimer: high sensitivity to thrombosis. D-dimer is elevated in acute pulmonary thromboembolism. If its level is normal, it has important diagnostic value for ruling out pulmonary thromboembolism, but has no confirmatory value for pulmonary thromboembolism due to poor specificity.

Arterial blood gas analysis: measures the oxygen and carbon dioxide levels in the blood. Pulmonary embolism often manifests as hypoxemia, hypocapnia, and increased alveolar-arterial oxygen partial pressure difference, and the blood gas results can be normal in some patients.

Other routine blood tests, such as routine blood tests, biochemistry, coagulation function, etc., are mainly used to exclude other diseases and assess the condition.

Imaging tests

X-ray chest radiograph: mainly used for preliminary judgment of pulmonary artery morphology, heart size, lung tissue changes, the presence of pleural effusion, etc. It is not a means to confirm the diagnosis.

Echocardiography: It is valuable in suggesting pulmonary thromboembolism and excepting other cardiovascular diseases, as well as performing risk stratification for acute pulmonary thromboembolism. The diagnosis is made if a thrombus is found in the right atrium or right ventricle and the patient’s clinical presentation is consistent with pulmonary thromboembolism.

Ultrasound of the veins of the lower extremities: the easiest way to diagnose deep vein thrombosis.

CT pulmonary arteriography (CTPA): a first-line diagnostic tool for pulmonary thromboembolism, capable of accurately detecting thrombi in pulmonary arteries above the segmental level.

Radionuclide pulmonary ventilation/perfusion (V/Q) imaging: an important diagnostic method for pulmonary thromboembolism. Typical signs are pulmonary perfusion defects in a segmental distribution and mismatch with ventilation imaging.

Magnetic Resonance Imaging and Magnetic Resonance Pulmonary Arteriography (MRI/MRPA): Magnetic Resonance Pulmonary Arteriography can directly visualize emboli in the pulmonary arteries and areas of hypoperfusion due to pulmonary thromboembolism, and can confirm the diagnosis, but is of limited diagnostic value in the diagnosis of pulmonary thromboembolism below the level of the lung segments. It may be used in patients with severely impaired renal function, allergy to iodine contrast agents, or pregnancy.

Pulmonary arteriography: The “gold standard” for the diagnosis of pulmonary thromboembolism. Pulmonary arteriography is an invasive test that carries a risk of fatal or serious complications and should be strictly indicated.

Other tests

Electrocardiogram (ECG): Most cases present with non-specific ECG abnormalities, the most common change being sinus tachycardia.

Differential diagnosis

Coronary atherosclerotic heart disease (CHD)

Similarities: chest tightness, chest pain.

Differences: Chest pain symptoms mostly appear after exercise or emotional excitement, chest pain can radiate to the upper limbs and back, and can be relieved after taking drugs to dilate the coronary arteries.

Pneumonia

Similarities: fever, cough, hemoptysis, dyspnea, chest pain.

Differences: Pneumonia has corresponding pulmonary and systemic infections, such as coughing up purulent sputum with chills and high fever, and antibiotic treatment is effective.

Aortic dissection

Similarities: chest pain, sweating, cold and clammy extremities.

Differences: aortic coarctation is characterized by high blood pressure, severe pain that radiates to the back, neck, waist, and even lower extremities, and differences in blood pressure and pulse rate between the upper extremities.

Acute pericarditis

Similarities: chest pain, fever.

Differences: Acute pericarditis may have more intense and persistent chest pain, aggravated by deep breathing and coughing; pericardial friction sounds appear in the early stage, and pericardial effusion disappears together with chest pain after the appearance of pericardial effusion.

Treatment

Treatment principle: the principle of acute pulmonary embolism is early diagnosis, early intervention, according to the patient’s risk stratification to choose the appropriate treatment program and treatment course.

General supportive treatment

For highly suspected or confirmed pulmonary thromboembolism, close supervision is required to monitor changes in respiration, heart rate, blood pressure, electrocardiogram and blood gases.

Bed rest, keep bowel movement unobstructed, and avoid exertion to avoid dislodgment of deep vein thrombus.

Symptomatic treatment, appropriate use of sedation, analgesia, cough and other appropriate symptomatic treatment.

Oxygen inhalation to correct hypoxemia, patients with respiratory failure can take the means of assisted ventilation.

For those who develop right heart insufficiency and blood pressure drop, dobutamine, dopamine and norepinephrine can be applied.

For those with combined hypertension, blood pressure should be controlled as much as possible.

Anticoagulation

Anticoagulation is the basic treatment for pulmonary thromboembolism and deep vein thrombosis, which can effectively prevent thrombus re-formation and recurrence.

Anticoagulant drugs mainly include ordinary heparin, low molecular weight heparin, sodium sulfadiazepoxide, warfarin and new direct oral anticoagulant drugs.

The anticoagulant effect of antiplatelet drugs cannot meet the anticoagulant requirements of pulmonary thromboembolism or deep vein thrombosis.

Anticoagulation therapy should be initiated when pulmonary thromboembolism is clinically suspected, if there are no contraindications.

Basal activated partial thromboplastin time (APTT), prothrombin time (PT) and blood routine (including platelet count, hemoglobin) should be measured before anticoagulation.

Oral anticoagulants: dabigatranate, rivaroxaban, apixaban, etc. These drugs have fewer interactions with food and drugs, do not require routine testing of coagulation indicators, and are more convenient to apply.

Other anticoagulants: including argatroban, bivalirudin, etc., are mainly used in patients who develop heparin-induced thrombocytopenia.

The general course of anticoagulation is at least 3 months. For first-ever cases with emboli of unknown origin, anticoagulation needs to be given for at least 6 months; for recurrent venous thromboembolism or prolonged presence of risk factors, anticoagulation should be more prolonged, up to 12 months or more, or even lifelong.

Thrombolytic therapy

Commonly used thrombolytic drugs are urokinase (UK), streptokinase (SK) and recombinant tissue-type fibrinogen activator (rt-PA).

They are mainly used in high-risk pulmonary thromboembolism cases (with significant dyspnea, chest pain, hypoxemia, etc.).

For some intermediate-risk pulmonary thromboembolism, thrombolysis may be considered if there are no contraindications.

In low-risk cases with normal blood pressure and right ventricular motility, thrombolysis is contraindicated.

Thrombolysis is usually performed within 14 days of the onset of the disease, but may be prolonged if there are recent signs of pulmonary thromboembolism. Thrombolysis should be performed as carefully as possible under the premise of confirmed diagnosis of pulmonary thromboembolism. Thrombolysis should be started as early as possible in cases with clear indications for thrombolysis.

The major complication of thrombolytic therapy is bleeding. The most serious is intracranial hemorrhage, with an incidence of 1% to 2%, and nearly half of those who experience it die.

Interventional therapy

Percutaneous catheter intervention can be used as an alternative treatment to surgical thrombectomy in patients with high-risk pulmonary embolism who have a contraindication to thrombolysis or failed thrombolysis in combination with hemodynamic instability (shock or hypotension).

Current interventional treatments for pulmonary embolism include: intracatheter thrombolysis, guidewire-guided catheter thrombus tamponade, local mechanical dissipation, balloon angioplasty, and the combination of intracatheter thrombolysis and thrombus tamponade.

In patients who fail anticoagulation or have absolute contraindications to anticoagulation, the installation of inferior vena cava filters may be considered after careful evaluation in order to prevent the re-dislodgement of large thrombi from the deep veins of the lower extremities from obstructing the pulmonary arteries.

Surgical treatment

The indications for pulmonary arteriotomy and thrombectomy in the treatment of acute pulmonary embolism are: large pulmonary embolism with shock, systolic blood pressure less than 100 mmHg, increased central venous pressure, renal failure, failure of thrombolytic therapy or emergency situation inappropriate for thrombolytic therapy.

Pulmonary thrombectomy can be used as an alternative remedy to systemic thrombolysis, but the medical institution must have the conditions and experience to perform the surgery.

Treatment of special cases

Pulmonary thromboembolism in combination with pregnancy

The effects of anticoagulant drugs on the mother and the fetus need to be fully considered during pregnancy.

Initial anticoagulant therapy should be low molecular heparin (LMH) injected subcutaneously and the dose should be adjusted according to body mass. Low molecular heparin is discontinued 12 hours before delivery.

Warfarin is not recommended during pregnancy.

Pulmonary thromboembolism combined with malignancy

Low molecular heparin anticoagulation should be chosen for 3 to 6 months in the acute phase of malignancy combined with pulmonary thromboembolism.

In active malignancy combined with pulmonary thromboembolism, after 3 months of anticoagulation, if the risk of bleeding is not high, prolonged anticoagulation or even lifelong anticoagulation is recommended.

Perioperative pulmonary thromboembolism

Acute high-risk pulmonary thromboembolism occurs in the early stage of surgery, with high bleeding risk on anticoagulation, thrombolytic therapy should be cautious, and intervention can be considered if necessary.

For patients with pulmonary thromboembolism on anticoagulation therapy who require surgery, the risk of recurrence of deep vein thrombosis after interruption of anticoagulation therapy should be evaluated against the risk of bleeding associated with the surgery, and the need to continue anticoagulation should be selected.

Chronic thromboembolic pulmonary hypertension

In patients with chronic thromboembolic pulmonary hypertension, lifelong anticoagulation is recommended, and warfarin is usually the anticoagulant of choice.

Surgical evaluation is recommended, and if surgery is possible, pulmonary endarterectomy (PEA) is preferred.

If pulmonary endarterectomy is not possible or residual pulmonary hypertension exists after surgery, targeted drug therapy, such as liothyronine, is recommended.

If pulmonary thromboendarterectomy cannot be performed or residual pulmonary hypertension exists after the procedure, interventional therapy is recommended if specialized expertise is available.

Prognosis

Cure

In some patients, after prompt treatment, the thrombus is naturally absorbed within weeks to months without significant complications or long-term adverse effects.

A small number of patients with acute pulmonary embolism are difficult to cure, and the emboli can be stabilized by treatment to prevent new emboli from forming, which may develop into chronic embolic pulmonary hypertension.

It has been shown that the 7-day all-cause-of-death morbidity and mortality rate for pulmonary thromboembolism ranges from 1.9% to 2.9%, and the 30-day all-cause-of-death morbidity and mortality rate ranges from 4.9% to 6.6%.

Data from follow-up studies suggest that peak mortality in patients with venous thromboembolism occurs within 6 months of initial treatment.

Recurrence of deep vein thrombosis or pulmonary embolism occurs most often 6 to 12 months after treatment. Recent data show that their 6-month recurrence rate is about 4.3%, 1-year recurrence rate is about 7.2%, and 10-year recurrence rate is about 35.4%. The recurrence rate is highest in the malignant tumor population.

Hazard

Pulmonary thromboembolism may be life-threatening. The hazard is associated with risk stratification, with a clinical mortality rate of >15% for high-risk pulmonary thromboembolism, 3% to 15% for intermediate-risk pulmonary thromboembolism, and <1% for low-risk pulmonary thromboembolism.

Pulmonary thromboembolism can also lead to pulmonary hypertension and even right heart failure.

Pulmonary thromboembolism can also lead to respiratory insufficiency, limiting the patient’s mobility and physical strength and affecting the quality of life.

Daily

Daily Management

Dietary management

Eat a light diet with reasonable nutrition. Foods containing vitamin K (e.g., kale, spinach, cabbage, lettuce) can interfere with the blood-thinning effect of warfarin, and patients taking warfarin should limit their intake of related foods.

Others

Use anticoagulant drugs as prescribed by your doctor.

Regularly test the coagulation function and adjust the drug dosage according to the coagulation function under doctor’s guidance.

Do not take aspirin or other over-the-counter medications without a doctor’s prescription.

Carry a label that reads “Taking Anticoagulants” with you at all times.

Go to the hospital as soon as bleeding is observed.

PREVENTION

Prevention in hospitalized patients

Encourage bedridden patients to move their limbs in bed. Patients who are immobile should be encouraged to perform passive joint mobilization, and to get down to the floor and walk as soon as their condition permits.

For patients who cannot move their legs, elevating the legs above the level of the heart can promote venous blood return in the lower limbs.

Bedridden patients can wear compression elastic anti-embolism stockings, application of lower extremity intermittent sequential compression pumps to promote lower extremity venous blood return.

Patients should increase fluid intake appropriately under doctor’s guidance to prevent blood concentration.

As hyperlipidemia and diabetes can lead to hypercoagulable state of blood, the original disease should be actively treated.

For patients at high risk of thrombosis, they should be instructed to use anticoagulant preparations as prescribed by doctors to prevent thrombosis.

Prevention of out-of-hospital patients

For people with risk factors for venous thromboembolism, prolonged sitting should be avoided, especially avoiding stilted legs while sitting, placing pillows under the knees while lying down, wearing knee stockings, and prolonged standing without activity.

Don’t sit for a long time, get up and move your body every 30 minutes.

Drink plenty of water.

Quit smoking and avoid alcohol.

Do not consume large amounts of coffee, strong tea and other beverages.

Control your weight.