(See also European Society of Cardiology 2019 Guidelines on Diagnosis and Management of Pulmonary Embolism.)
Pulmonary embolism affects an estimated 117 people per 100,000 person years, resulting in about 350,000 cases in the US each year and causing up to 100,000 deaths/year. It affects mainly adults.
Etiology of Pulmonary Embolism
Nearly all pulmonary emboli arise from thrombi in the veins of the legs or pelvis (deep venous thrombosis Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more ). Risk of embolization is higher with thrombi that reach the popliteal vein or above. Thromboemboli can also originate in arm veins or central veins of the chest (caused by central venous catheters or resulting from thoracic outlet syndromes).
Pulmonary embolism can also arise from nonthrombotic sources Nonthrombotic Pulmonary Embolism Nonthrombotic sources of pulmonary embolism include air, fat, amniotic fluid, infected material, foreign bodies, and tumors. Pulmonary embolism (PE) can arise from nonthrombotic sources. PE... read more (eg, embolism of air, amniotic fluid, fat, infected material, foreign body, tumor).
Risk factors for deep venous thrombosis and pulmonary embolism (see table Risk Factors for Deep Venous Thrombosis and Pulmonary Embolism Risk Factors for Deep Venous Thrombosis and Pulmonary Embolism ) are similar in children and adults and include
Conditions that impair venous return, including bed rest and confinement without walking
Conditions that cause endothelial injury or dysfunction
Underlying hypercoagulable (thrombophilic) disorders such as cancer or primary clotting disorders Overview of Thrombotic Disorders In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip... read more
COVID-19 COVID-19 COVID-19 is an acute, sometimes severe, respiratory illness caused by the novel coronavirus SARS-CoV-2. Prevention is by vaccination and infection control precautions (eg, face masks, handwashing... read more appears to be a risk factor for deep venous thrombosis and pulmonary embolism. Although part of the risk may be due to reduced mobility associated with illness, it is thought that SARS-CoV-2 infection is particularly prothrombotic.
Pathophysiology of Pulmonary Embolism
Once deep venous thrombosis develops, clots may dislodge and travel through the venous system and the right side of the heart to lodge in the pulmonary arteries, where they partially or completely occlude one or more vessels. The consequences depend on the size and number of emboli, the underlying condition of the lungs, how well the right ventricle (RV) is functioning, and the ability of the body’s intrinsic thrombolytic system to dissolve the clots. Death occurs due to right ventricular failure.
Small emboli may have no acute physiologic effects and may begin to lyse immediately and resolve within hours or days. Larger emboli can cause a reflex increase in ventilation (tachypnea), hypoxemia due to ventilation/perfusion (V/Q) mismatch and low mixed venous oxygen content as a result of low cardiac output, atelectasis due to alveolar hypocapnia and abnormalities in surfactant, and an increase in pulmonary vascular resistance caused by mechanical obstruction and vasoconstriction resulting in tachycardia and hypotension. Endogenous lysis reduces most emboli, even those of moderate size, and physiologic alterations decrease over hours or days. Some emboli resist lysis and may organize and persist and sometimes cause chronic pulmonary hypertension.
Pulmonary emboli may be classified according to the physiologic effects as
High risk (catastrophic or super-massive): Impaired right ventricular function with severe hypotension/hypoxemia that requires aggressive pressor therapy and high-flow oxygen
High risk (massive): Impaired right ventricular function causing hypotension, as defined by systolic blood pressure < 90 mm Hg or a drop in systolic blood pressure of ≥ 40 mm Hg from baseline for a period of 15 minutes
Intermediate risk (submassive): Impaired right ventricular function and/or abnormal troponin and/or brain (B-type) natriuretic peptide (BNP) level without hypotension. Note that the European Society of Cardiology defines intermediate-risk pulmonary embolism also as patients with a simplified pulmonary embolism severity index (sPESI) of > 0, thus including patients with other disorders or findings.
Low risk: Absence of right ventricular impairment and absence of hypotension (and by European Society of Cardiology, sPESI score = 0)
Intermediate-risk patients can be subdivided into intermediate-high risk (abnormal right ventricle by echocardiography AND elevated troponin) and intermediate-low risk (abnormal right ventricle by echocardiography OR elevated troponin).
Saddle pulmonary embolism describes a pulmonary embolus that lodges in the bifurcation of the main pulmonary artery and into the right and left pulmonary arteries; saddle emboli are usually, but not always, intermediate or high-risk. A saddle configuration does not dictate a specific therapeutic approach. Although saddle emboli are often large and cause complete obstruction, they may be a relatively thin, nonobstructive embolus.
In 1 to 3% of cases, chronic residual obstruction leads to pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension is increased pressure in the pulmonary circulation. It has many secondary causes; some cases are idiopathic. In pulmonary hypertension, pulmonary vessels may become constricted... read more (chronic thromboembolic pulmonary hypertension) that evolves over months to years and can result in chronic right heart failure.
When a large embolus acutely occlude major pulmonary arteries or when many smaller emboli combine to occlude > 50% of the more distal vessels, RV pressure increases, which may lead to acute RV failure RV failure Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more , shock, or sudden death. The risk of death depends on the degree and rate of rise of right-sided pressures and on the patient’s underlying cardiopulmonary status. Patients with preexisting cardiopulmonary disease are at higher risk of death, but young and/or otherwise healthy patients may survive a PE that occludes > 50% of the pulmonary bed.
Pulmonary infarction (interruption of pulmonary artery blood flow leading to ischemia of lung tissue , sometimes represented by a pleural-based [peripherally located], often wedge-shaped, pattern on chest x-ray [Hampton hump] or other imaging modalities) occurs in < 10% of patients diagnosed with PE. This low rate has been attributed to the dual blood supply to the lung (ie, bronchial and pulmonary). Generally, pulmonary infarction is due to smaller emboli that become lodged in more distal pulmonary arteries and is nearly always completely reversible; pulmonary infarction is recognized early, using sensitive radiographic criteria, often before necrosis occurs.
Symptoms and Signs of Pulmonary Embolism
Many pulmonary emboli are small, physiologically insignificant, and asymptomatic. Even when present, symptoms are nonspecific and vary in frequency and intensity, depending on the extent of pulmonary vascular occlusion and preexisting cardiopulmonary function.
Emboli often cause
Pleuritic chest pain (when there is pulmonary infarction)
Dyspnea may be minimal at rest and can worsen during activity.
Less common symptoms include
Cough (usually caused by comorbid disorders)
Hemoptysis (occasionally occurs when there is pulmonary infarction)
In elderly patients, the first symptom may be altered mental status.
Massive pulmonary emboli may manifest with hypotension, tachycardia, light-headedness/presyncope, syncope, or cardiac arrest.
The most common signs of pulmonary embolism are
Less commonly, patients have hypotension. A loud 2nd heart sound (S2) due to a loud pulmonic component (P2) is possible but uncommon in acute PE because increases in pulmonary artery pressures are only modest. Crackles or wheezing may occur but is usually due to comorbid disease. In the presence of right ventricular failure, distended internal jugular veins and a RV heave may be evident, and a RV gallop (3rd heart sound [S3]), with or without tricuspid regurgitation, may be audible.
Fever, when present, is usually low-grade unless caused by an underlying condition.
Pulmonary infarction is typically characterized by chest pain (mainly pleuritic) and, occasionally, hemoptysis. The chest wall may be tender.
Chronic thromboembolic pulmonary hypertension causes symptoms and signs of right heart failure, including exertional dyspnea, easy fatigue, and peripheral edema that develops over months to years.
Patients with acute pulmonary embolism may also have symptoms of deep venous thrombosis Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more (ie, pain, swelling, and/or erythema of a leg or an arm). Such leg symptoms are often not present, however.
Diagnosis of Pulmonary Embolism
High index of suspicion
Assessment of pretest probability (based on clinical findings, including pulse oximetry and chest x-ray)
Subsequent testing based on pretest probability
The diagnosis of pulmonary embolism is challenging because symptoms and signs are nonspecific and diagnostic tests are not 100% sensitive and specific. It is important to include PE in the differential diagnosis when nonspecific symptoms, such as dyspnea, pleuritic chest pain, hemoptysis, light-headedness, or syncope are encountered. Thus, PE should be considered in the differential diagnosis of patients suspected of having
Acute anxiety with hyperventilation
Significant, unexplained tachycardia may be a clue. Pulmonary embolism also should be considered in any older patient with tachypnea and altered mental status.
Initial evaluation should include pulse oximetry and chest x-ray. ECG, arterial blood gas (ABG) measurements, or both may help to exclude other diagnoses (eg, acute myocardial infarction Acute Myocardial Infarction (MI) Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and/or diaphoresis... read more ).
The chest x-ray usually is nonspecific but may show atelectasis, focal infiltrates, an elevated hemidiaphragm, or a pleural effusion. The classic findings of focal loss of vascular markings (Westermark sign), a peripheral, wedge-shaped density arising from the pleura (Hampton hump), or enlargement of the right descending pulmonary artery are suggestive but uncommon (ie, insensitive) and have low specificity. Chest x-ray can also help exclude pneumonia. Pulmonary infarction due to pulmonary embolism may be mistaken for pneumonia.
Pulse oximetry provides a quick way to assess oxygenation; hypoxemia is one sign of PE, and it requires further evaluation. Blood gas testing should be considered particularly for patients with dyspnea or tachypnea who do not have hypoxemia detected with pulse oximetry. Arterial or venous blood gas measurement Arterial Blood Gas (ABG) Sampling Gas exchange is measured through several means, including Diffusing capacity for carbon monoxide Pulse oximetry Arterial blood gas sampling The diffusing capacity for carbon monoxide (DLCO)... read more may show an increased alveolar to arterial oxygen (A-a) difference (sometimes called A-a gradient) or hypocapnia. Both of these tests are moderately sensitive for PE, but neither is specific. Blood gas testing should be considered particularly for patients with dyspnea or tachypnea who do not have hypoxemia detected with pulse oximetry. Oxygen saturation may be normal due to a small clot burden, or to compensatory hyperventilation; a very low pCO2 detected with an ABG measurement can confirm hyperventilation.
ECG most often shows tachycardia and various ST-T wave abnormalities, which are not specific for pulmonary embolism (see figure An ECG in pulmonary embolism An ECG in pulmonary embolism ). An S1Q3T3 or a new right bundle branch block may indicate the effect of abrupt rise in RV size affecting RV conduction pathways; these findings are moderately specific but insensitive, occurring in only about 5% of patients, although the findings occur in a higher percentage of patients with massive PE. Right axis deviation (R > S in V1) and P-pulmonale may be present. T-wave inversion in leads V1 to V4 also occurs.
An ECG in pulmonary embolism
The ECG shows sinus tachycardia at a rate of 110 beats/minute, an S1Q3T3 and R = S in V1 in a patient with proven acute pulmonary embolism.
Clinical probability of pulmonary embolism can be assessed by combining ECG and chest x-ray findings with findings from the history and physical examination. Clinical prediction scores, such as the Wells score or the revised Geneva score (1 Diagnosis reference Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more ), or the Pulmonary Embolism Rule-Out Criteria (PERC) rule, may aid clinicians in assessing the chance that acute pulmonary embolism is present. These prediction scores assign points to a variety of clinical factors, with cumulative scores corresponding to designations of the probability of PE before testing (pretest probability). For example, the Wells score result is classified as likely or unlikely for PE. Clinical probability scoring has been best studied in patients presenting to the emergency department.
One of the important clinical criteria is a judgment of whether PE is more likely than an alternate diagnosis, and this determination is somewhat subjective. However, the clinical judgment of experienced clinicians is as sensitive as, or even more sensitive, than results from formal prediction scores. PE should probably be considered more likely if one or more of the symptoms and signs, particularly dyspnea, hemoptysis, tachycardia, or hypoxemia, cannot be explained clinically or by chest x-ray results.
Pretest probability guides testing strategy and the interpretation of test results. In patients in whom the probability of PE is unlikely, only minimal additional testing (ie, D-dimer testing in outpatients) may be needed. In such cases, a negative D-dimer test (< 0.4 mcg/mL [< 2.2 nmol/L]) is highly indicative of the absence of pulmonary embolism. Conversely, if there is a high clinical suspicion of PE and the risk of bleeding is low, immediate anticoagulation should be considered while the diagnosis is confirmed with additional tests.
The PERC rule specifies 8 criteria. Presence of these criteria in a clinically low-risk patient specifies that testing for PE is not indicated. The criteria are:
Age < 50 years
HR < 100
Oxygen saturation ≥ 95%
No prior deep venous thrombosis or pulmonary embolism
No unilateral leg swelling
No estrogen use
No surgery or trauma requiring hospitalization within the past 4 weeks
Use of the PERC rule has been recommended as a way to decrease rates of testing for PE with conventional testing using D-dimer, but with similar rates of sensitivity and negative predictive values.
Screening of outpatients with D-dimer testing if pre-test probability is low or of intermediate probability
If pretest probability is likely or if D-dimer result is elevated, CT angiography, or if renal insufficiency is present or when CT contrast is contraindicated, with ventilation/perfusion (V/Q) scanning
Sometimes ultrasonography of the legs or arms (to confirm DVT when lung imaging is delayed or prohibitive)
There is no universally accepted algorithm for the approach to suspected acute pulmonary embolism. Tests most useful for diagnosing or excluding PE are
Echocardiography may be useful to identify pulmonary embolism on the way to the lung (clot-in-transit).
D-Dimer is a by-product of intrinsic fibrinolysis; thus, elevated levels occur in the presence of a recent thrombus. When pretest probability is considered low or intermediate, a negative D-dimer level (< 0.4 mcg/mL [< 2.2 nmol/L]) is highly sensitive for the absence of PE with a negative predictive value of > 95%; in most cases, this result is sufficiently reliable for excluding the diagnosis of PE in the outpatient setting such as the emergency department or clinic. However, elevated D-dimer levels are not specific for venous thrombus because many patients without deep venous thrombosis (DVT) or PE also have elevated levels (particularly in the inpatient setting), and therefore, further testing is required when the D-dimer level is elevated or when the pretest probability for PE is high.
CT angiography is the preferred imaging technique for diagnosing acute pulmonary embolism. It is rapid, accurate, and highly sensitive and specific. It can also give more information about other lung pathology (eg, demonstration of pneumonia rather than PE as a cause of hypoxia or pleuritic chest pain) as well as severity of PE (for example by the size of the right ventricle or the reflux into the hepatic veins). Although poor quality scans due to motion artifact or poor contrast boluses can limit the sensitivity of the examination, improvements in CT technology have shortened acquisition times to less than 2 seconds, providing relatively motion-free images in patients who are dyspneic. Fast scanning times allow the use of smaller volumes of iodinated contrast, which reduces the risk of acute kidney injury.
The sensitivity of CT angiography is highest for pulmonary embolism in the main pulmonary artery and lobar and segmental vessels. Sensitivity of CT angiography is lowest for emboli in subsegmental vessels (about 30% of all pulmonary emboli). However, the sensitivity and specificity of CT angiography have improved as technology has evolved.
Ventilation/perfusion (V/Q) scans in pulmonary embolism detect areas of lung that are ventilated but not perfused. V/Q scanning takes longer than CT angiography and is less specific. However, when chest x-ray findings are normal or near normal and no significant underlying lung disease exists, it is a highly sensitive test. V/Q scanning is particularly useful when renal insufficiency precludes the use of contrast that is otherwise required for CT angiography. In some hospitals, V/Q scanning can be done with a portable machine that provides 3 views of ventilation and perfusion, which is useful when a patient is too ill to move. Perfusion defects may occur in many other lung conditions (eg, COPD Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more , pulmonary fibrosis Idiopathic Pulmonary Fibrosis Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, causes progressive pulmonary fibrosis. Symptoms and signs develop over months to years and include... read more , pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more , pleural effusion Pleural Effusion Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and usually are classified as transudates or exudates. Detection is by physical examination and... read more ). Mismatched perfusion defects that may mimic PE may occur in pulmonary vasculitis, pulmonary veno-occlusive disease, and sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more .
Results are based on patterns of V/Q mismatch and typically are reported as
Normal: Excludes PE with nearly 100% accuracy
Very low probability: < 5%
Low probability: 15% likelihood of PE
Intermediate probability: 30 to 40% probability of PE
High probability: 80 to 90% probability of PE
The results of clinical probability testing must be used together with the scan result to determine the need for treatment or further testing.
Duplex ultrasonography is a safe, noninvasive, portable technique for detecting leg or arm thrombi. A clot can be detected by showing poor compressibility of the vein or by showing reduced flow by Doppler ultrasonography. The test has a sensitivity of > 95% and a specificity of > 95% for thrombus. Confirming DVT in the calf or iliac veins can be more difficult but can generally be accomplished. The ultrasound technician should always attempt to image below the popliteal vein into its trifurcation.
Absence of thrombi in the leg veins does not exclude the possibility of thrombus from other sources, such as the upper extremities, but patients with suspected DVT and negative results on Doppler duplex ultrasonography have > 95% event-free survival, because thrombi from other sources are so much less common.
Although ultrasonography of the legs or arms is not diagnostic for PE, a study that reveals leg or axillary-subclavian thrombus establishes the need for anticoagulation and may obviate the need for further diagnostic testing unless more aggressive therapy (eg, thrombolytic therapy) is being considered. Therefore, stopping the diagnostic evaluation after detection of DVT on ultrasonography of the legs or arms is most appropriate for stable patients with contraindications to CT contrast and in whom V/Q scanning is expected to have low specificity (eg, in patients with an abnormal chest x-ray). In suspected acute PE, a negative ultrasound does not negate the need for additional studies.
Pearls & Pitfalls
Echocardiography may show a clot in the right atrium or ventricle, but echocardiography is most commonly used for risk stratification in acute PE. The presence of right ventricular dilation and hypokinesis may suggest the need for more aggressive therapy.
Cardiac marker testing is evolving as a useful means of stratifying mortality risk in patients with acute pulmonary embolism. Cardiac marker testing can be used as an adjunct to other testing if PE is suspected or proven. Elevated troponin levels signify right ventricular (or sometimes left ventricular) ischemia. Elevated brain natriuretic peptide (BNP) and pro-BNP levels may signify RV dysfunction; however, these tests are not specific for RV dysfunction or for PE.
Thrombotic disorder (thrombophilia) testing should be considered for patients with PE and no known risk factors, especially if they are younger, have recurrent PE, or have a positive family history. Certain thrombophilias, such as antiphospholipid antibody syndrome Antiphospholipid Antibody Syndrome (APS) Antiphospholipid antibody syndrome is an autoimmune disorder in which patients have autoantibodies to phospholipid-bound proteins. Venous or arterial thrombi may occur. The pathophysiology is... read more , require disease-specific types of anticoagulation therapy. SARS-CoV-2 should be considered in the appropriate clinical setting.
Pulmonary arteriography is now rarely needed to diagnose acute PE because noninvasive CT angiography has similar sensitivity and specificity. However, in patients in whom catheter-based thrombolytic therapy is being used, pulmonary angiography is useful for assessment of catheter placement and may be used as a rapid means of determining success of the procedure when the catheter is removed. Pulmonary arteriography is also still used together with right-heart catheterization in assessing whether patients with chronic thromboembolic pulmonary hypertension are candidates for pulmonary endarterectomy.
1. Le Gal G, Righini M, Roy PM, et al: Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 144:165–171, 2006.
Prognosis for Pulmonary Embolism
An estimated 10% of patients with pulmonary embolism die within the first few hours after presentation. Most patients who die as a result of acute PE are never diagnosed before death. In fact, PE is not suspected in most of these patients. The best prospects for reducing mortality involve
Improving the frequency of diagnosis (eg, by including PE in the differential diagnosis when patients present with nonspecific but compatible symptoms or signs)
Improving the rapidity of diagnosis
Improving the rapidity of initiation of anticoagulation therapy
Providing appropriate prophylaxis in at-risk patients
Very high D-dimer levels appear to predict a poor outcome.
Patients with chronic thromboembolic disease represent a small, but important fraction of patients with PE who survive. Anticoagulant therapy reduces the rate of recurrence of PE to about 5%, and some studies have found anticoagulants reduce recurrence rates even lower.
General Treatment of Pulmonary Embolism
Inferior vena cava filter placement (in selected patients)
Rapid clot burden reduction (in selected patients)
Rapid assessment for the need for supportive therapy should be undertaken. In patients with hypoxemia, oxygen should be given. In patients with hypotension due to massive PE, 0.9% saline can be cautiously given IV; overloading the right ventricle can result in deterioration. Vasopressors may also be given if IV fluids fail to sufficiently increase blood pressure. Norepinephrine is the most commonly used first-line agent. Epinephrine and dobutamine have inotropic effects, but it is not clear how much these affect the normally thin-walled RV.
Low-risk patients should receive anticoagulation alone
High-risk / catastrophic patients require anticoagulation plus additional measures such as systemic thrombolysis or surgical or catheter-directed therapy
Intermediate-risk patients (high or low) are more complicated. Intermediate-low risk patients are most commonly treated with anticoagulation alone. However, the intermediate-risk categories require assessment of their entire clinical picture including
Symptoms and signs
Severity of RV dysfunction by echocardiography
Degree of troponin elevation
Amount of oxygen and vasopressor required
Clot burden and location
Many hospitals in the US and other countries now use a multidisciplinary group of clinicians (pulmonary embolus response team) to rapidly evaluate and risk-stratify patients with pulmonary embolism and make the complex treatment decisions needed. These teams may be comprised of clinicians in pulmonary/critical care medicine, interventional cardiology, cardiothoracic surgery, hematology, and other specialties (1 General treatment reference Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more ).
Anticoagulation Anticoagulation Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more is the mainstay of therapy for PE, and rapid reduction of clot burden Rapid Reduction of Clot Burden Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more via thrombolytic therapy or embolectomy is indicated for patients with hypotension that does not resolve after fluid resuscitation, and for selected patients with impaired RV function. Placement of a removable percutaneous inferior vena cava filter (IVCF) should be considered for patients with contraindications to anticoagulation or for those with recurrent PE despite anticoagulation. For example, patients who have acute PE and residual clot in the leg and cannot be anticoagulated, should have a filter placed because they have persistent risk of subsequent DVT.
Hospitalization for at least 24 to 48 hours is done for most patients with PE. Patients with abnormal vital signs or massive or submassive PE require longer periods of hospitalization.
ICU admission is always required for massive PE. ICU admission should also be considered if patients have
Extensive clot burden
Low or borderline blood pressure
Outpatient management may be used for select patients with incidentally discovered PE or those with very small clot burdens and minimal symptoms provided their vital signs are stable, education is undertaken, and a reasonable plan for outpatient treatment and follow-up is in place.
General treatment reference
1. Kabrhel C, Jaff MR, Channick RN, et al: A multidisciplinary pulmonary embolism response team. Chest 144(5):1738–1739, 2013. doi: 10.1378/chest.13-1562
Initial anticoagulation followed by maintenance anticoagulation is indicated for patients with acute pulmonary embolism to prevent clot extension and further embolization as well as new clot formation. Anticoagulant therapy for acute PE should be started whenever PE is strongly suspected, as long as the risk of bleeding is deemed low. Otherwise, anticoagulation should be started as soon as the diagnosis is made. The likelihood of benefit versus harm in treating emboli in smaller, subsegmental vessels (particularly asymptomatic and incidentally discovered emboli) is currently unknown, and it is possible that in certain settings harm may outweigh benefit. Still, treatment is currently recommended. The primary complication of anticoagulation therapy is bleeding, and patients should be closely observed for bleeding during hospitalization.
Initial anticoagulation choices for acute PE include
Intravenous unfractionated heparin
Subcutaneous low molecular weight heparin
Factor Xa inhibitors (apixaban and rivaroxaban)
Intravenous argatroban for patients with heparin-induced thrombocytopenia
Intravenous unfractionated heparin has a short half-life (useful when the potential for bleeding is deemed higher than usual) and is reversible with protamine. An initial bolus of unfractionated heparin is given, followed by an infusion of heparin dosed by protocol to achieve an activated PTT 1.5 to 2.5 times that of normal control (see figure Weight-based heparin dosing Weight-based dosing ). Therefore, unfractionated heparin requires ongoing hospitalization to administer. Further, the pharmacokinetics of unfractionated heparin are relatively unpredictable, resulting in frequent periods of over-anticoagulation and under-anticoagulation and necessitating frequent dose adjustments. Regardless, many clinicians prefer this IV unfractionated heparin regimen, particularly when thrombolytic therapy is given or contemplated or when patients are at risk of bleeding because if bleeding occurs, the short half-life means that anticoagulation is quickly reversed after the infusion is stopped.
Subcutaneous low molecular weight heparin has several advantages over unfractionated heparin including
Weight-based dosing results in a more predictable anticoagulation effect than does weight-based dosing of unfractionated heparin
Ease of administration (can be given subcutaneously once or twice a day)
Decreased incidence of bleeding
Potentially better outcomes
The potential for patients to self-inject (thereby allowing earlier discharge from the hospital)
Lower risk of heparin-induced thrombocytopenia compared with standard, unfractionated heparin
In patients with renal insufficiency, dose reductions are needed (see table Some Low Molecular Weight Heparin Options in Thromboembolic Disease Some Low Molecular Weight * Options in Thromboembolic Disease ), and subsequent verification of appropriate dosing should be done by checking serum factor Xa levels (target: 0.5 to 1.2 IU/mL measured at 3 to 4 hours after the 4th dose). Low molecular weight heparins are generally contraindicated in patients with severe renal insufficiency (creatinine clearance < 30 mL/minute). Low molecular weight heparins are partially reversible with protamine.
Adverse effects of all heparins include
Thrombocytopenia (including heparin-induced thrombocytopenia Heparin-induced thrombocytopenia Platelet destruction can develop because of immunologic causes (viral infection, drugs, connective tissue or lymphoproliferative disorders, blood transfusions) or nonimmunologic causes (sepsis... read more with the potential for thromboembolism)
Bleeding caused by over-heparinization with unfractionated heparin can be treated with a maximum of 50 mg of protamine per 5000 units unfractionated heparin infused over 15 to 30 minutes. Over-heparinization with a low molecular weight heparin can be treated with protamine 1 mg in 20 mL normal saline infused over 10 to 20 minutes, although the precise dose is undefined because protamine only partially neutralizes low molecular weight heparin inactivation of factor Xa.
Fondaparinux is a factor Xa antagonist given subcutaneously. It can be used in acute DVT and acute PE instead of heparin or low molecular weight heparin. It has also been shown to prevent recurrences in patients with superficial venous thrombosis. Outcomes appear to be similar to those of unfractionated heparin. Advantages include once or twice a day fixed-dose administration, no need for monitoring of the degree of anticoagulation, and lower risk of thrombocytopenia. The dose (in mg/kg once a day) is 5 mg for patients < 50 kg, 7.5 mg for patients 50 to 100 kg, and 10 mg for patients > 100 kg. Fondaparinux dose is decreased by 50% if creatinine clearance is 30 to 50 mL/minute (0.5 to 0.83 mL/second). The drug is contraindicated if creatinine clearance is < 30 mL/minute.
The other factor Xa inhibitors, apixaban, rivaroxaban, and edoxaban, have the advantages of oral fixed dosing and the ability to be used as maintenance anticoagulants Maintenance anticoagulation Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more with no need for laboratory monitoring of the anticoagulant effect. They also cause few adverse interactions with other drugs, although azole antifungal therapy and older HIV therapies (protease inhibitors) will increase oral factor Xa inhibitor drug levels, and certain antiseizure drugs and rifampin will decrease oral factor Xa inhibitor drug levels. Although rivaroxaban and apixaban do not require overlap with a parenteral anticoagulant when used as initial therapy, edoxaban requires use of a parenteral anticoagulant for 5 to 10 days.
Dose reductions are indicated for patients with renal insufficiency. Apixaban can be used in patients with renal insufficiency and data suggest use is safe in patients undergoing hemodialysis.
Anticoagulation reversal of the oral Xa inhibitors (rivaroxaban, apixaban, edoxaban) is possible with andexanet, although this drug is not widely used at this time. Also, the half-lives of the newer factor Xa inhibitors are much shorter than the half-life for warfarin. If bleeding develops that requires reversal, use of 4-factor prothrombin complex concentrate can be considered, and hematology consultation is recommended.
The safety and efficacy of these drugs in patients with pulmonary embolism complicated by severe cardiopulmonary decompensation have not yet been studied, and parenteral drugs should be used for anticoagulation in these patients until there is significant improvement in cardiopulmonary function.
The direct thrombin inhibitor dabigatran has also proven effective for treatment of acute DVT and PE. Idarucizumab has proven effective at reversing dabigatran.
Finally, in patients with suspected or proven heparin-induced thrombocytopenia Heparin-induced thrombocytopenia Platelet destruction can develop because of immunologic causes (viral infection, drugs, connective tissue or lymphoproliferative disorders, blood transfusions) or nonimmunologic causes (sepsis... read more , intravenous argatroban or subcutaneous fondaparinux can be used for anticoagulation. Use of the direct oral anticoagulants is currently being studied in patients with heparin-induced thrombocytopenia, but these drugs appear safe after platelet recovery.
Maintenance anticoagulation is indicated to reduce the risk of clot extension or embolization and to reduce the risk of new clot formation. Drug choices for maintenance anticoagulation include
Oral vitamin K antagonist (warfarin in the US)
Oral factor Xa inhibitors (apixaban, rivaroxaban, edoxaban)
Oral direct thrombin inhibitor (dabigatran)
Rarely subcutaneous low molecular weight heparin
Warfarin is an effective long-term oral anticoagulant option that has been used for decades, but it is very inconvenient for a number of reasons. In most patients, warfarin is started on the same day as heparin (or fondaparinux) therapy used for initial anticoagulation. Heparin (or fondaparinux) therapy should be overlapped with warfarin therapy for a minimum of 5 days and until the INR has been within the therapeutic range (2.0 to 3.0) for at least 24 hours.
The major disadvantages of warfarin are the need for periodic INR monitoring, with frequent dose adjustments, and drug interactions. Physicians prescribing warfarin should be wary of drug interactions; in a patient taking warfarin, virtually any new drug should be checked.
Bleeding is the most common complication of warfarin treatment; patients > 65 years and those with comorbidities (especially diabetes, recent myocardial infarction, hematocrit < 30%, or creatinine > 1.5 mg/dL [>133 micromol/L]) and a history of stroke or gastrointestinal bleeding seem to be at greatest risk. Bleeding can be reversed with vitamin K 2.5 to 10 mg IV or orally and, in an emergency, with fresh frozen plasma or a new concentrate formulation (prothrombin complex concentrates) containing factor II (prothrombin), factor VII, factor IX, factor X, protein C, and protein S. Vitamin K may cause flushing, local pain, and, rarely, anaphylaxis.
Warfarin-induced necrosis, a devastating complication of warfarin therapy, can occur in patients with heparin-induced thrombocytopenia Heparin-induced thrombocytopenia Platelet destruction can develop because of immunologic causes (viral infection, drugs, connective tissue or lymphoproliferative disorders, blood transfusions) or nonimmunologic causes (sepsis... read more if warfarin is started before platelet recovery. Based on these considerations and the development of more convenient oral anticoagulants, it is likely that warfarin use will decline substantially over the coming years.
Pearls & Pitfalls
The oral factor Xa inhibitor anticoagulants apixaban and rivaroxaban can be used for both initial and maintenance anticoagulation therapy (see table Oral Anticoagulants Oral Anticoagulants ). These drugs are more convenient than warfarin due to their fixed dosing and lack of need for laboratory monitoring, as well as having fewer drug interactions. In clinical trials, rivaroxaban (1, 2 Anticoagulation references Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more ), apixaban (3 Anticoagulation references Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more ), and edoxaban (4 Anticoagulation references Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more ) were as effective (in non-inferiority analyses) as warfarin in preventing recurrent DVT and PE. A meta-analysis of large phase III randomized controlled trials found that rates of major bleeding, including intracranial hemorrhage, were significantly lower with oral factor Xa inhibitor anticoagulants than with warfarin (5 Anticoagulation references Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more ). Another advantage of both rivaroxaban and apixaban is that dosages may be lowered (10 mg orally once a day of rivaroxaban and 2.5 mg orally twice a day of apixaban) after patients have been treated for 6 to 12 months.
Edoxaban requires that a preceding 5 to 10 days of initial heparin or low molecular weight heparin be given.
The direct thrombin inhibitor dabigatran can also be used for maintenance anticoagulation therapy. As with edoxaban, 5 to 10 days of treatment with unfractionated heparin or low molecular weight heparin is needed before dabigatran can be initiated. Clinically relevant bleeding is lower with dabigatran than with warfarin. The use of dabigatran as maintenance therapy has the same advantages and disadvantages as the use of the factor Xa inhibitors.
The need for initial heparin treatment before edoxaban or dabigatran is given is a reflection of the way the clinical trials were conducted.
Subcutaneous low molecular weight heparin is primarily used for high-risk cancer patients or patients with recurrent pulmonary embolism despite other anticoagulants. The SELECT-D trial suggested efficacy of rivaroxaban in cancer patients (6 Anticoagulation references Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more ).
Aspirin has been studied for long-term maintenance therapy. It appears more effective than placebo but less effective than all other available anticoagulants. Rivaroxaban, 10 mg once/day, has proven more effective at reducing recurrent DVT/PE yet is as safe as aspirin in patients already treated with anticoagulation for 6 to 12 months (7 Anticoagulation references Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more ).
Duration of anticoagulation
Duration of maintenance anticoagulation for PE is dependent on a variety of factors (eg, risk factors for PE, bleeding risk) and can range from 3 months to lifelong therapy. Clearly transient risk factors (eg, immobilization, recent surgery, trauma) require only 3 months of treatment. Patients with unprovoked PE, those with more durable risk factors for PE (eg, cancer, thrombophilic disorder), and those with recurrent PE might benefit from lifelong anticoagulation provided the bleeding risk is low or moderate. In many patients, degree of risk is less clear (eg, with a minor precipitating factor such as a 4 hour flight); for them, rather than stopping rivaroxaban or apixaban at 6 months, dosage can be decreased.
Risk factors for bleeding include
Age > 65 years
Poor anticoagulant control
Reduced functional capacity
Low risk for bleeding is defined as no bleeding risk factors, moderate risk for bleeding is defined as one risk factor, and high risk for bleeding is defined as two or more risk factors.
As described above, after 6 months of treatment with rivaroxaban or apixaban, dosage decreases can be considered.
1. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al: Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363(26):2499–2510, 2010.
2. EINSTEIN-PE Investigators, Buller HR, Prins MH, et al: Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366 (14):1287–1297, 2012.
3. Agnelli G, Buller HR, Cohen A, et al: Oral apixaban for the treatment of acute venous thromboembolism.N Engl J Med 369(9):799–808, 2013.
4. Hokusai-VTE Investigators, Buller HR, Decousus H, et al: Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369(15): 1406–1415, 2013.
5. van Es N, Coppens M, Schulman S, et al: Direct oral anticoagulants compared with vitamin K antagonists for acute symptomatic venous thromboembolism: evidence from phase 3trials. Blood124 (12): 1968–1975, 2014.
6. Young AM, Marshall A, Thirlwall J, et al: Comparison of an oral factor Xa inhibitor with LMWH in patients with cancer with VTE Results of a randomized trial (SELECT-D). J Clin Oncol 36 (20):2017–2029, 2018.
7. Weitz JI, Lensing AWA, Prins MH, et al: Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 376:1211–1222, 2017. doi: 10.1056/NEJMoa1700518. Epub 2017 Mar 18.
Rapid Reduction of Clot Burden
Clot elimination by means of embolectomy or dissolution with IV or catheter-based thrombolytic therapy should be considered for acute pulmonary embolism associated with hypotension that does not resolve after fluid resuscitation (massive PE). Patients who are hypotensive and require vasopressor therapy are obvious candidates. Patients with a systolic blood pressure < 90 mm Hg lasting at least 15 minutes are hemodynamically compromised and are also candidates.
Although only anticoagulation is generally recommended for patients with very mild RV dysfunction (based on clinical, ECG, or echocardiographic findings), thrombolytic therapy or embolectomy may be needed when RV compromise and/or hypoxemia is severe even when hypotension is not present, particularly when deterioration is likely as suggested by an increase in heart rate or decrease in oxygen saturation or blood pressure.
Systemic thrombolytic therapy
Systemic thrombolytic therapy with alteplase (tissue plasminogen activator [tPA]) offers a noninvasive way to rapidly restore pulmonary blood flow, but use is controversial because long-term benefits do not clearly outweigh the risk of hemorrhage. Regardless, most experts agree that systemic thrombolytic therapy should be given to patients with hemodynamic compromise, particularly when it is severe. Although no single prospective randomized trial of systemic thrombolytic therapy has shown improved survival in patients with submassive PE, some experts recommend thrombolytics, particularly when patients also have numerous or large clots, very severe RV dysfunction, marked tachycardia, significant hypoxemia, and other concomitant findings such as residual clot in the leg, positive troponin values, and/or elevated BNP values. Others reserve thrombolytic therapy only for patients with massive (high-risk) PE. Streptokinase and urokinase generally are no longer used.
Absolute contraindications to thrombolytics include
Prior hemorrhagic stroke
Ischemic stroke within 1 year
Active external or internal bleeding from any source
Intracranial injury or surgery within 2 months
Certain surgeries within the previous few days
Relative contraindications include
Recent surgery (≤ 10 days)
Hemorrhagic diathesis (as in hepatic insufficiency)
Recent punctures of large noncompressible veins (eg, subclavian or internal jugular veins)
Recent femoral artery catheterization (eg, ≤ 10 days)
Peptic ulcer disease or other conditions that increase the risk of bleeding
Severe hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg)
Head trauma from PE-induced syncope, even if brain CT is normal
Except for concurrent intracerebral hemorrhage, thrombolytic therapy is sometimes given to patients with massive PE who have "absolute contraindications" to such therapy if death is otherwise expected. In patients with relative contraindications, the decision to give systemic thrombolytics depends on individual patient factors.
In the US, alteplase (tPA) is used for systemic thrombolysis (see table Regimens for Systemic Thrombolysis Regimens for Systemic Thrombolysis ). Streptokinase and urokinase are no longer used for acute PE.
In the US, when systemic thrombolytics are given, heparin is usually stopped after the initial loading dose. However, in Europe, heparin is often continued, and there is no clear determination as to which method is preferred. The bleeding risk should be considered.
Bleeding, if it occurs, can be reversed with cryoprecipitate or fresh frozen plasma. Accessible vascular access sites that are bleeding can be compressed. The potential for bleeding after systemic thrombolysis has led to increased implementation of catheter-based thrombolysis, because much lower doses of thrombolytic agents are used.
Catheter-directed PE therapy (thrombolytics, embolectomy) uses catheter placement in the pulmonary arteries for disruption and/or lysis of clot. It is used to treat massive PE. Indications for the treatment of submassive PE are evolving. Studies to date, including prospective randomized clinical trials, have demonstrated that this approach leads to an improved RV/LV ratio at 24 hours compared with anticoagulation alone. Other outcomes and safety of catheter-based therapy compared to systemic thrombolysis are under investigation.
In catheter-based PE thrombolytic therapy, the pulmonary arteries are accessed via a typical right-heart catheterization/pulmonary arteriography procedure, and thrombolytics are delivered directly to large proximal emboli via the catheter. The most widely studied technique uses high-frequency, low-power ultrasonography to facilitate delivery of the thrombolytics. Ultrasonography accelerates the thrombolytic process by disaggregating fibrin strands and increasing permeability of lytic drug into the clot. Standard dosing has been 20 to 24 mg of tPA over 15 or more hours, but lower doses and shorter durations have been shown to be effective with this technique.
Other clot extraction techniques involve catheter-directed vortex suction embolectomy, sometimes in combination with extracorporeal bypass. Catheter-directed vortex suction embolectomy differs from systemic thrombolysis and catheter-based PE thrombolytic therapy in that a larger bore catheter is required and blood that is suctioned out must be redirected out back into a vein (usually femoral). Patients with venal caval, right atrial, or right ventricular thrombi-in-transit are the best candidates. The pulmonary arteries are difficult to access with the current devices. Veno-arterial extracorporeal membrane oxygenation (ECMO) may be used as a rescue procedure in severely ill patients with acute PE, regardless of what other therapies are used. Other smaller suctioning devices are now available.
Surgical embolectomy is reserved for patients with PE who are hypotensive despite supportive measures (persistent systolic blood pressure ≤ 90 mm Hg after fluid therapy and oxygen or if vasopressor therapy is required) or on the verge of cardiac or respiratory arrest. Surgical embolectomy should be considered if use of thrombolysis is contraindicated; in such cases, catheter-directed vortex embolectomy may also be considered and, depending on local resources and expertise, tried before surgical embolectomy. Surgical embolectomy appears to increase survival in patients with massive PE but is not widely available. As with catheter-based thrombosis/clot extraction, the decision to proceed with embolectomy and the choice of technique depend on local resources and expertise.
Extracorporeal membrane oxygenation
Extracorporeal membrane oxygenation (ECMO) has been used increasingly in catastrophic acute pulmonary embolism when thrombolysis is contraindicated or failed. ECMO may serve as a bridge to surgical embolectomy or catheter-directed therapy, or it may buy time for improvement with anticoagulation alone.
Prevention of Pulmonary Embolism
Prevention of acute venous thromboembolism
Prevention of pulmonary embolism means prevention of deep venous thrombosis (DVT); the need depends on the patient’s risks, including
Type and duration of any surgery
Comorbid conditions, including cancer and hypercoagulable disorders
Presence of a central venous catheter
Prior history of DVT or PE
Bedbound patients and patients undergoing surgical, especially orthopedic, procedures benefit, and most of these patients can be identified before a thrombus forms (see table Risk Assessment for Thrombosis Risk Assessment for Thrombosis ). Preventive measures include low-dose unfractionated heparin, low molecular weight heparin, warfarin, fondaparinux, oral anticoagulants (eg, rivaroxaban, apixaban), compression devices, and elastic compression stockings.
Choice of drug or device depends on various factors, including the patient population, the perceived risk, contraindications (eg, bleeding risk), relative costs, and ease of use. The American College of Chest Physicians has published comprehensive evidence-based recommendations for prophylaxis of acute DVT, including the duration of prophylaxis, in surgical and nonsurgical patients and during pregnancy (The American College of Chest Physicians most recent Guidelines on Prevention of Thrombosis) . The need for prophylaxis has been studied in numerous patient populations.
The type of surgery as well as patient-specific factors determine the risk of DVT. Independent risk factors include
Age ≥ 60 years
Prior DVT or PE
Anesthesia ≥ 2 hours
Bed rest ≥ 4 days
Hospital stay ≥ 2 days
Pregnancy or the postpartum state
Central venous access
Body mass index (BMI) > 40
The Caprini score is commonly used for DVT risk stratification and determination of the need for DVT prophylaxis in surgical patients (see table Risk Assessment for Thrombosis Risk Assessment for Thrombosis ).
The need for DVT prophylaxis is based on the risk assessment score (see table Prophylaxis Based on Caprini Score Prophylaxis Based on Caprini Score ). Appropriate preventive measures, ranging from early ambulation to use of heparin, depend on the total score.
Drug regimens for pulmonary embolism prevention
Drug therapy to prevent DVT is usually begun after surgery to help prevent intraoperative bleeding. However, preoperative prophylaxis is also effective.
In general surgery patients, low dose unfractionated heparin is given in doses of 5000 units subcutaneously every 8 to 12 hours for 7 to 10 days or until the patient is fully ambulatory. Immobilized patients not undergoing surgery should receive 5000 units subcutaneously every 8 to 12 hours until they are ambulatory.
Low molecular weight heparin dosing for DVT prophylaxis Prevention Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more depends on the specific drug (enoxaparin, dalteparin, tinzaparin). Low molecular weight heparins are at least as effective as low dose unfractionated heparin for preventing DVT and PE.
Fondaparinux 2.5 mg sc once/day is as effective as low molecular weight heparin for orthopedic surgery and in some other settings. It is a selective factor Xa inhibitor.
Warfarin is usually effective and safe at a dose of 2 to 5 mg orally once a day or at a dose adjusted to maintain an INR of 2 to 3 in patients who have undergone total hip or knee replacement. It is still used by some orthopedic surgeons for prophylaxis in these patients but is increasingly being supplanted by the use of the direct oral anticoagulants.
Rivaroxaban, an oral factor Xa inhibitor, is used for prevention of acute DVT/PE in patients undergoing total knee or hip arthroplasty. The dose is 10 mg orally once a day. Its use in other patients (surgical and nonsurgical) is currently under investigation.
Apixaban, an oral factor Xa inhibitor, is also used for prevention of acute DVT/PE in patients undergoing total knee or hip arthroplasty. The dose is 2.5 mg orally twice a day. Like rivaroxaban, its use in other types of patients is currently under investigation.
Prophylactic devices for pulmonary embolism
Inferior vena cava filters, intermittent pneumatic compression (also known as sequential compression devices [SCD]), and graded elastic compression stockings may be used alone or in combination with drugs to prevent PE. Whether these devices are used alone or in combination depends on the specific indication.
An inferior vena cava filter (IVCF) may help prevent PE in patients with DVT in the leg, but IVCF placement may risk long-term complications. Benefits outweigh risk if a second PE is predicted to be life-threatening; however, few clinical trial data are available. A filter is most clearly indicated in patients who have:
Proven DVT and contraindications to anticoagulation
Recurrent DVT (or emboli) despite adequate anticoagulation
Undergone pulmonary thromboendarterectomy
Marginal cardiopulmonary function, causing concern for their ability to tolerate additional small emboli (occasionally)
Because venous collaterals can develop, providing a pathway for emboli to circumvent the IVCF, and because filters occasionally thrombose, patients with recurrent DVT or nonmodifiable risk factors for DVT may still require anticoagulation. An IVCF is placed in the inferior vena cava just below the renal veins via catheterization of an internal jugular or femoral vein. Most IVCFs are removable. Occasionally, a filter dislodges and may migrate up the venous bed, even to the heart, and needs to be removed or replaced. A filter can also become thrombosed, causing bilateral venous congestion (including acute phlegmasia cerulea dolens) in the leg, lower body ischemia, and acute kidney injury.
Intermittent pneumatic compression (IPC) with SCDs provides rhythmic external compression to the legs or to the legs and thighs. It is more effective for preventing calf than proximal DVT. It is insufficient as sole prophylaxis after hip or knee replacement but is often used in low-risk patients after other types of surgery or in medical patients who have a low-risk of DVT or who are at high risk of bleeding. IPC can theoretically trigger PE in immobilized patients who have developed occult DVT while not receiving DVT prophylaxis.
Graded elastic compression stockings are likely less effective than external pneumatic leg compression, but one systematic meta-analysis suggested that they reduced the incidence of DVT in postoperative patients from 26% in the control group to 13% in the compression stockings group.
Choices for prevention of pulmonary embolism
After surgical procedures with a high incidence of DVT/PE, low dose unfractionated heparin, low molecular weight heparin, or adjusted-dose warfarin is recommended.
After orthopedic surgery of the hip or knee, additional options include the direct oral anticoagulants, rivaroxaban and apixaban. These drugs are safe and effective and do not require laboratory tests to monitor the level of anticoagulation as is needed for warfarin.
For total hip arthroplasty, patients should continue to take anticoagulants for 35 days postoperatively. In selected patients at very high risk of both DVT/PE and bleeding, temporary placement of an IVCF is an option for prophylaxis.
A high risk of DVT/PE also occurs in patients undergoing elective neurosurgery and those with acute spinal cord injury and multiple trauma. Although physical methods (SCDs and elastic stockings) have been used in neurosurgical patients because of concern about intracranial bleeding, low molecular weight heparin appears to be an acceptable alternative. The combination of SCDs and low molecular weight heparin may be more effective than either alone in high-risk patients. Limited data support the combination of SCDs, elastic compression stockings, and low molecular weight heparin in patients with spinal cord injury or in multiple trauma. For very high-risk patients, a temporary IVCF may be considered.
In acutely ill medical patients, low dose unfractionated heparin, low molecular weight heparin, or fondaparinux can be given. SCDs, elastic compression stockings, or both may be used when anticoagulants are contraindicated. For ischemic stroke patients, low dose unfractionated heparin or low molecular weight heparin can be used; SCD, elastic compression stockings, or both may be beneficial.
Acute PE is a common and potentially devastating medical condition.
Clinical suspicion and a confirmatory diagnosis are essential because in most patients who die from acute PE, PE is not even suspected.
Because anticoagulation improves survival, patients should be anticoagulated when PE is diagnosed or strongly suspected.
Patients with massive PE and certain patients with submassive PE should be considered for thrombolytic therapy or embolectomy.
Prevention of deep vein thrombosis (and thus PE) should be considered in all at-risk hospitalized patients.
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Konstantinides SV, Meyer G, Becattini C, et al: 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ehz405
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|Adrenaclick, Adrenalin, Auvi-Q, Epifrin, EpiPen, Epipen Jr , Primatene Mist, SYMJEPI, Twinject|
|Hepflush-10 , Hep-Lock, Hep-Lock U/P, Monoject Prefill Advanced Heparin Lock Flush, SASH Normal Saline and Heparin|
|Xarelto, Xarelto Granules, Xarelto Starter Pack|
|No brand name available|
prothrombin complex concentrate
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|Activase, Cathflo Activase|