Epidemiology and pathogenesis of acute pulmonary embolism in adults

INTRODUCTION — Acute pulmonary embolism (PE) is a form of venous thromboembolism (VTE) that is common and sometimes fatal. The clinical presentation of PE is variable and often nonspecific making the diagnosis challenging. The evaluation of patients with suspected PE should be efficient so that patients can be diagnosed and therapy administered quickly to reduce the associated morbidity and mortality.

The definition, epidemiology, pathogenesis, and pathophysiology of PE are discussed in detail in this topic. A detailed discussion of the diagnosis and treatment of PE is provided separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults".) (Related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically stable and Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically unstable despite resuscitative efforts and Pulmonary embolism (confirmed or suspected): Initial management of hemodynamically stable adults and Pulmonary embolism (confirmed or suspected): Initial management of hemodynamically unstable adults.)

DEFINITION AND NOMENCLATURE

Definition — Pulmonary embolus (PE) refers to obstruction of the pulmonary artery or one of its branches by material (eg, thrombus, tumor, air, or fat) that originated elsewhere in the body. This topic review focuses upon PE due to thrombus. Tumor, air, and fat emboli are discussed separately. (See "Pulmonary tumor embolism and lymphangitic carcinomatosis in adults: Diagnostic evaluation and management" and "Air embolism" and "Fat embolism syndrome".)

Nomenclature — PE can be classified by the following:

●The temporal pattern of presentation (acute, subacute, or chronic) – Patients with PE can present acutely, subacutely, or chronically:

•Acute – Patients with acute PE typically develop symptoms and signs immediately after obstruction of pulmonary vessels.

•Subacute – Some patients with PE may also present subacutely within days or weeks following the initial event.

•Chronic – Patients with chronic PE slowly develop symptoms of pulmonary hypertension over many years (ie, chronic thromboembolic pulmonary hypertension; CTEPH).

An overview of acute and subacute PE is discussed in this review. The etiology, clinical manifestations, diagnosis, and treatment of CTEPH are discussed separately. (See "Epidemiology, pathogenesis, clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension" and "Chronic thromboembolic pulmonary hypertension: Initial management and evaluation for pulmonary artery thromboendarterectomy".)

●The presence or absence of hemodynamic stability (hemodynamically unstable or stable) – Hemodynamically unstable PE is also called "massive" or "high-risk" PE. Hemodynamically stable PE is called "submassive" or "intermediate-risk" PE if there is associated right ventricular strain, or "low-risk" PE if there is no evidence of right ventricular strain. Hemodynamically stable and unstable PE are defined as the following:

•Hemodynamically unstable PE is that which results in hypotension. Hypotension is defined as a systolic blood pressure <90 mmHg or a drop in systolic blood pressure of ≥40 mmHg from baseline for a period >15 minutes or hypotension that requires vasopressors or inotropic support and is not explained by other causes such as sepsis, arrhythmia, left ventricular dysfunction from acute myocardial ischemia or infarction, or hypovolemia. Although hemodynamically unstable PE is often caused by large (ie, massive) PE, it can sometimes be due to small PE in patients with underlying cardiopulmonary disease. Thus, the term "massive" PE does not necessarily describe the size of the PE as much as its hemodynamic effect. (See 'Pathophysiologic response to PE' below.)

•Hemodynamically stable PE is defined as PE that does not meet the definition of hemodynamically unstable PE. There is a spectrum of severity within this population ranging from patients who present with small, mildly symptomatic or asymptomatic PE (also known as "low-risk PE") to those who present with mild or borderline hypotension that stabilizes in response to fluid therapy, or those who present with right ventricle dysfunction (also known as "submassive" or "intermediate-risk" PE).

The distinction between hemodynamically stable and unstable PE is important because patients with hemodynamically unstable PE are more likely to die from obstructive shock (ie, severe right ventricular failure). Importantly, death from hemodynamically unstable PE often occurs within the first two hours, and the risk remains elevated for up to 72 hours after presentation [1,2]. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Hemodynamically unstable patients' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Prognosis' and "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration", section on 'Hemodynamically unstable patients (high-risk pulmonary embolism)'.)

●The anatomic location (saddle, lobar, segmental, subsegmental) – Saddle PE lodges at the bifurcation of the main pulmonary artery, often extending into the right and left main pulmonary arteries. Approximately 3 to 6 percent of patients with PE present with a saddle embolus [3,4]. Traditionally, saddle PE was thought to be associated with hemodynamic instability and death. However, retrospective studies suggest that among those diagnosed with a saddle embolus, only 22 percent are hemodynamically unstable, with an associated mortality of 5 percent [3,4]. Clot that is "in transit" through the heart is often classified as a form of PE, even though the thrombus has not yet lodged in a pulmonary artery. Clot-in-transit is associated with high mortality (up to 40 percent).

Most PE move beyond the bifurcation of the main pulmonary artery to lodge distally in the main lobar, segmental, or subsegmental branches of a pulmonary artery. PE can be bilateral or unilateral, depending on whether they obstruct arteries in the right, left, or both lungs. Smaller thrombi that are located in the peripheral segmental or subsegmental branches are more likely to cause pulmonary infarction and pleuritis (image 1). (See 'Pathophysiologic response to PE' below.)

●The presence or absence of symptoms (symptomatic or asymptomatic) – Symptomatic PE refers to the presence of symptoms that usually leads to the radiologic confirmation of PE, whereas asymptomatic PE refers to the incidental finding of PE on imaging (eg, contrast-enhanced computed tomography performed for another reason) in a patient without symptoms. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Diagnosis'.)

EPIDEMIOLOGY

General population — Estimates of the incidence of pulmonary embolism (PE) in the general population increased following the introduction of D-dimer testing and computed tomographic pulmonary angiography in the 1990s [5-11]. However, studies since then have reported stable rates [10,12]. As an example, reported an incidence rate of PE as 0.38 per 1000 person years, a rate that appeared to be stable between 2002 and 2012 [10]. Another study a reported rate of 2.81 per 100,000 in 2019, which was similar to that in 2006 [12].

The overall incidence is higher in males compared with females (56 versus 48 per 100,000, respectively) [12-15]. The incidence rises with increasing age, particularly in women, such that PE has an incidence of >500 per 100,000 after the age of 75 years [14,16]. The use of statins, exercising regularly, and a low body mass index may reduce the incidence of PE [17].

In the United States, PE accounts for approximately 100,000 annual deaths [13,18]. In Europe, PE accounts for 300,000 deaths annually [19]. In an analysis based upon data from five European countries, the majority of VTE-related deaths were due to hospital-acquired PE and most were diagnosed antemortem [20]. However, many causes of sudden cardiac death are thought to be secondary to PE, so the actual mortality attributable to PE is difficult to estimate.

Deaths from diagnosed PE have been declining [8,13,21], with one study reporting deaths from PE that decreased between 1979-1998, from 191 to 94 per million [13]. In another study, the mortality risk ratio from PE declined from 138 (95% CI, 125-153) in 1980-1989 to 36.08 (95% CI, 32.65-39.87) in 2000-2011 [22].

Overall mortality from PE appears to be high. Another study reported a 30-day and 1 year mortality at 4 and 13 percent, respectively and a case-fatality rate that increased with increasing age [10].

In a review of death certificates in the Multiple-Cause Mortality Files compiled by the National Center for Health Statistics from 1979 to 1998, age-adjusted mortality rates were 50 percent higher in African American compared with White American adults; in turn, mortality rates in White Americans were 50 percent higher compared with other groups (eg, Asian American, American Indian) [13].

Special populations — The incidence of venous thromboembolism (DVT and PE) in select populations is discussed in the following sections:

●Patients with malignancy (see "Risk and prevention of venous thromboembolism in adults with cancer", section on 'Incidence and risk factors' and "Supportive care for locally advanced or metastatic exocrine pancreatic cancer", section on 'Venous thromboembolism' and "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy")

●Patients who are pregnant

●Patients with stroke (see "Prevention and treatment of venous thromboembolism in patients with acute stroke")

●Hospitalized medical patients (see "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'General medical patients')

●Hospitalized surgical patients (see "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients")

●Hospitalized gynecologic patients (see "Risk and prevention of venous thromboembolism in adults with cancer", section on 'Incidence and risk factors')

●Patients with nephrotic syndrome (see "Hypercoagulability in nephrotic syndrome", section on 'Epidemiology')

●Patients with acute traumatic spinal cord injury (see "Acute traumatic spinal cord injury", section on 'Venous thromboembolism and pulmonary embolism')

●Patients with total joint arthroplasty or replacement (see "Complications of total knee arthroplasty", section on 'Thromboembolism' and "Complications of total hip arthroplasty", section on 'Venous thromboembolism')

●Patients with inherited thrombotic disorders (see "Overview of the causes of venous thrombosis", section on 'Inherited thrombophilia')

PATHOGENESIS AND PATHOPHYSIOLOGY

Pathogenesis — The pathogenesis of pulmonary embolism (PE) is similar to that which underlies the generation of thrombus (ie, Virchow's triad). Virchow's triad consists of venous stasis, endothelial injury, and a hypercoagulable state, which is discussed separately. (See "Overview of the causes of venous thrombosis", section on 'Virchow triad'.)

Risk factors — The few studies that have specifically examined risk factors for PE alone confirm that they are similar to those for venous thromboembolism (VTE) in general [23-29]. Risk factors can be classified as inherited (ie, genetic) and acquired. More than 50 genetic risk factors for VTE have been identified, including factor V Leiden and the prothrombin gene mutation (20210-A) [30-33]. Acquired risk factors can be further sub-classified as provoking (eg, recent surgery, trauma, immobilization, initiation of hormone therapy, active cancer) or non-provoking (eg, obesity, heavy cigarette smoking) [29]. Risk factors for VTE are discussed in detail separately. (See "Overview of the causes of venous thrombosis".)  

Source — Most emboli are thought to arise from lower extremity proximal veins (iliac, femoral, and popliteal) (table 1) and more than 50 percent of patients with proximal vein deep venous thrombosis (DVT) have concurrent PE at presentation [34-38]. Calf vein DVT rarely embolizes to the lung and two–thirds of calf vein thrombi resolve spontaneously after detection [39-48]. However, if untreated, one-third of calf vein DVT extend into the proximal veins, where they have greater potential to embolize. PE can also arise from DVT in non-lower-extremity veins including renal and upper extremity veins, although embolization from these veins is less common. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Distal DVT'.)

Most thrombi develop at sites of decreased flow in the lower extremity veins, such as valve cusps or bifurcations. However, they may also originate in veins with higher venous flow including the inferior vena cava, or the pelvic veins, and in non-lower-extremity veins including renal and upper extremity veins. (See "Hypercoagulability in nephrotic syndrome" and "Overview of thoracic central venous obstruction".)

Pathophysiologic response to PE — Pulmonary emboli are typically multiple, with the lower lobes being involved in the majority of cases [49]. Once thrombus lodges in the lung, a series of pathophysiologic responses can occur:

●Infarction – In about 10 percent of patients, small thrombi lodge distally in to the segmental and subsegmental vessels resulting in pulmonary infarction [50]. These patients are more likely to have pleuritic chest pain and hemoptysis, presumed to be due to an intense inflammatory response in the lung and adjacent visceral and parietal pleura.

●Abnormal gas exchange – Impaired gas exchange from PE is due to mechanical and functional obstruction of the vascular bed altering the ventilation to perfusion ratio, and from inflammation resulting in surfactant dysfunction and atelectasis resulting in functional intrapulmonary shunting. Both mechanisms cause hypoxemia [51]. Inflammation is also thought to be responsible for stimulating respiratory drive resulting in hypocapnia and respiratory alkalosis. Hypercapnia and acidosis are unusual in PE unless shock is present. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Laboratory tests' and "Measures of oxygenation and mechanisms of hypoxemia".)

●Cardiovascular compromise – Hypotension from PE is due to diminished stroke volume and cardiac output. In patients with PE, pulmonary vascular resistance (PVR) is increased due to physical obstruction of the vascular bed with thrombus and hypoxic vasoconstriction within the pulmonary arterial system. Increased PVR, in turn, impedes right ventricular outflow and causes right ventricular dilation and flattening or bowing of the intraventricular septum. Both diminished flow from the right ventricle (RV) and RV dilation reduce left ventricular preload thereby compromising cardiac output.

As an example, when obstruction of the pulmonary vascular bed approaches 75 percent, the RV must generate a systolic pressure in excess of 50 mmHg to preserve adequate pulmonary artery flow [52]. When the RV is unable to accomplish this, it fails and hypotension ensues. Thus, in patients without underlying cardiopulmonary disease, multiple large thrombi are generally responsible for hypotension via this mechanism. By contrast, in patients with underlying cardiopulmonary disease, especially those with pre-existing elevations in PVR, hypotension can be induced by smaller emboli, likely due to a substantial vasoconstrictive response and/or an inability of the RV to generate sufficient pressure to combat high PVR.

CLINICAL PRESENTATION, EVALUATION, AND DIAGNOSIS

Clinical presentation — Pulmonary embolism (PE) has a wide variety of presenting features, ranging from no symptoms to shock or sudden death. The most common presenting symptom is dyspnea followed by chest pain (classically pleuritic in nature, but not always), cough, and symptoms of deep venous thrombosis. Hemoptysis is an unusual presenting symptom. With severe PE, patients can present with shock, arrhythmia, or syncope. Many patients, including some with large PE, are asymptomatic or have mild or nonspecific symptoms. Thus, it is critical that a high level of suspicion be maintained such that clinically relevant cases are not missed. The signs and symptoms of PE are discussed in detail separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Clinical presentation'.)

Diagnostic approach to patients with suspected PE — For most patients with suspected PE who are hemodynamically stable, we suggest an approach which combines clinical and pretest probability assessment (calculator 1) (table 2), D-dimer testing, and definitive diagnostic imaging (algorithm 1 and algorithm 2 and algorithm 3). Definitive imaging includes computed tomographic pulmonary angiography and less commonly, ventilation perfusion scanning or other imaging modalities. For patients who are hemodynamically unstable and in whom definitive imaging is unsafe, bedside echocardiography or venous compression ultrasound may be used to obtain a presumptive diagnosis of PE to justify the administration of potentially life-saving therapies.

Details regarding the evaluation and diagnostic approach to patients with suspected PE are discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".) (Related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically stable and Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically unstable despite resuscitative efforts.)

TREATMENT — When a patient presents with suspected acute pulmonary embolism (PE), initial resuscitative therapy should focus upon oxygenating and stabilizing the patient. Resuscitative therapy may range from supplemental oxygen to ventilatory and hemodynamic support. Intravenous fluid resuscitation should be limited, as further distention of an already dilated right ventricle (RV) can worsen hemodynamics. If possible, endotracheal intubation should be avoided, as positive pressure ventilation can reduce preload and compress the failing RV, leading to hemodynamic collapse. An overview of the general measures used to resuscitate patients with suspected PE is discussed in detail separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults".)

Once the diagnosis is made, the mainstay of therapy for patients with confirmed PE is anticoagulation, depending upon the risk of bleeding. When the pre-test probability of PE is high or diagnostic imaging will be delayed, anticoagulation is sometimes started before a diagnosis of PE is confirmed. Data that support initial, long-term, and indefinite anticoagulation, and factors that determine whether or not a patient can be treated in the outpatient setting (ie, without hospitalization), are discussed separately. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation" and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Outpatient anticoagulation' and "Venous thromboembolism: Initiation of anticoagulation".) (Related Pathway(s): Pulmonary embolism (confirmed or suspected): Initial management of hemodynamically stable adults and Pulmonary embolism (confirmed or suspected): Initial management of hemodynamically unstable adults.)

Patients with life-threatening PE may require additional treatment beyond anticoagulation, including thrombolysis, inferior vena cava filters, and embolectomy. Select populations that require specific anticoagulation or alternative treatment strategies include:

●Patients with malignancy (see "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy")

●Patients who are pregnant (see "Venous thromboembolism in pregnancy and postpartum: Treatment" and "Use of anticoagulants during pregnancy and postpartum")

●Patients with heparin-induced thrombocytopenia (see "Clinical presentation and diagnosis of heparin-induced thrombocytopenia" and "Management of heparin-induced thrombocytopenia")

●Patients with a contraindication to anticoagulation (inferior vena cava filter placement) (see "Placement of vena cava filters and their complications" and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Inferior vena cava filter')

●Patients who are hemodynamically unstable or fail anticoagulation (thrombolytic therapy and/or embolectomy) (see "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration" and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Embolectomy')

PROGNOSIS — The major adverse outcomes associated with pulmonary embolism (PE) include the following:

●Recurrent thromboembolism – The recurrence rate depends upon factors including adequate therapeutic anticoagulation and the clinical nature of the embolic event (eg, provoked, unprovoked), the details of which are discussed separately. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)

●Chronic thromboembolic pulmonary hypertension (CTEPH) – CTEPH is an uncommon (1 to 4 percent) late outcome of patients with PE. The prognosis of patients with CTEPH is discussed separately. (See "Chronic thromboembolic pulmonary hypertension: Initial management and evaluation for pulmonary artery thromboendarterectomy".)  

●Death – PE left untreated is associated with an overall mortality of up to 30 percent. Mortality is significantly reduced with anticoagulation. Most deaths attributable to PE occur during the first week following diagnosis (early mortality) and are due to shock and recurrent venous thromboembolism. However, many deaths following PE are due to predisposing comorbidities or are multifactorial. One study demonstrated increased risk of death for up to eight years in patients without comorbidities [53], while other studies have reported that mortality remains increased for as long as 30 years (long-term mortality) with death mostly due to predisposing comorbidities (eg, cardiovascular disease, malignancy, sepsis) [22]. Details regarding the mortality of patients diagnosed with PE are discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Morbidity and mortality'.)

Prognostic models that incorporate clinical findings with or without laboratory tests can predict death and/or recurrence. Among prognostic models, the Pulmonary Embolism Severity Index (PESI), the simplified PESI (sPESI), and the Hestia Criteria [54] are the most well known (table 3) and predict all-cause mortality after PE. A detailed discussion of the prognostic value of these and other models is presented separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Prognostic factors' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Prognostic models'.)

MONITORING AND FOLLOW-UP — Patients with pulmonary embolism (PE) should be monitored for the following:

●Laboratory evidence of therapeutic efficacy in patients receiving unfractionated heparin and/or warfarin. (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Warfarin administration' and "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects" and "Heparin and LMW heparin: Dosing and adverse effects", section on 'Laboratory monitoring and dose titration (unfractionated heparin)'.)

●Early complications of PE, predominantly recurrent thromboembolism and progression of the diagnosed PE. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Clinical presentation'.) Patients with confirmed recurrent PE while on therapy should be evaluated for sub-therapeutic anticoagulation or, if anticoagulation is adequate, other causes of recurrence. Investigating and managing the early complications of PE, including recurrence, are discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Monitoring and follow-up' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Management of recurrence on therapy'.)

●Late complications of PE, mostly, chronic thromboembolic pulmonary hypertension CTEPH. Most patients who develop CTEPH do so in the first two years following PE and the diagnosis is usually suspected clinically because of persistent symptoms. The clinical presentation and diagnosis of CTEPH are discussed separately. (See "Epidemiology, pathogenesis, clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension".)

●Complications of therapy for PE, including bleeding and adverse effects of medication or devices. (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Complications' and "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects" and "Placement of vena cava filters and their complications", section on 'Complications' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Embolectomy' and "Heparin and LMW heparin: Dosing and adverse effects", section on 'Other complications' and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Mitigating bleeding risk' and "Risks and prevention of bleeding with oral anticoagulants" and "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration", section on 'Efficacy'.)

●The risk of recurrence and bleeding. The risk of recurrence and bleeding should be periodically assessed during therapy and, again, at the end of therapy to assess the need for indefinite anticoagulation. Assessing recurrence and bleeding risk as well as indications for indefinite anticoagulation are discussed separately. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)

●The need for device removal. Patients who had an inferior vena cava filter placed because anticoagulation was contraindicated should, once the contraindication has resolved, initiate anticoagulant therapy and have the filter retrieved, if feasible. (See "Placement of vena cava filters and their complications", section on 'Filter retrieval'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Pulmonary embolism (blood clot in the lung) (The Basics)")

●Beyond the Basics topics (see "Patient education: Pulmonary embolism (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition and nomenclature

•Pulmonary embolism (PE) is a common and sometimes fatal disease. It is due to obstruction of a pulmonary artery or one of its branches by material (eg, thrombus, tumor, air, or fat) that originated elsewhere in the body. (See 'Definition' above.)

•PE can be classified according to the following (see 'Nomenclature' above):

-The presence or absence of hemodynamic stability (hemodynamically unstable or stable)

-The temporal pattern of presentation (acute, subacute, or chronic),

-The anatomic location (saddle, lobar, segmental, subsegmental)

-The presence or absence of symptoms (symptomatic or asymptomatic).

Patients with hemodynamically unstable PE, defined as a systolic blood pressure <90 mmHg or a drop in systolic blood pressure of ≥40 mmHg from baseline for >15 minutes, should be distinguished from patients with hemodynamically stable PE because they are more likely to die from obstructive shock in the first two hours of presentation and may therefore benefit from more aggressive treatment.

●Epidemiology – The overall incidence of PE is approximately 112 cases per 100,000. PE is slightly more common in males than females and incidence increases with age. Deaths from PE account for approximately 100,000 deaths per year in the United States. (See 'Epidemiology' above.)

●Pathogenesis – The pathogenesis of PE is similar to that of deep venous thrombosis. Most emboli arise from lower extremity proximal veins (iliac, femoral, and popliteal) (table 1). However, they may also originate in right heart, inferior vena cava or the pelvic veins, and in the renal and upper extremity veins. (See "Overview of the causes of venous thrombosis" and 'Pathogenesis and pathophysiology' above.)

●Presentation and diagnosis

•Presentation – PE has a wide variety of presenting features, ranging from no symptoms to shock or sudden death. The most common presenting symptom is dyspnea followed by chest pain, cough, and symptoms of deep venous thrombosis. Further details are provided separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and 'Clinical presentation, evaluation, and diagnosis' above.)

•Diagnosis – For most patients with suspected PE we suggest an approach which combines clinical and pretest probability assessment (calculator 1) (table 2), D-dimer testing, and definitive diagnostic imaging, usually computed tomographic pulmonary angiography and, less commonly, ventilation perfusion scanning (algorithm 1 and algorithm 2 and algorithm 3). Further details are provided separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and 'Diagnostic approach to patients with suspected PE' above.) (Related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically stable and Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically unstable despite resuscitative efforts.)

●Treatment and prognosis

•Initial resuscitative therapy for patients with suspected PE should focus upon oxygenating and stabilizing the patient. Once the diagnosis is made, the mainstay of therapy for patients with confirmed PE is anticoagulation, depending upon the risk of bleeding. Alternative treatments include thrombolysis, inferior vena cava filters, and embolectomy. Further details are provided separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults" and 'Treatment' above.) (Related Pathway(s): Pulmonary embolism (confirmed or suspected): Initial management of hemodynamically stable adults and Pulmonary embolism (confirmed or suspected): Initial management of hemodynamically unstable adults.)

•PE can be complicated by recurrent thrombosis, chronic thromboembolic pulmonary hypertension (CTEPH), and death. PE left untreated, has an overall mortality of up to 30 percent, which is significantly reduced with anticoagulation. Prognostic models that incorporate clinical findings (eg, Pulmonary Embolism Severity Index [PESI] and the simplified PESI [sPESI] (table 3) and the Hestia Criteria) with or without laboratory tests can predict death and/or recurrence. Further details are provided separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Prognosis' and 'Prognosis' above.)

●Follow-up – Patients treated with unfractionated heparin and/or warfarin should be monitored for laboratory evidence of therapeutic efficacy. In addition, patients should be monitored for the early and late complications of PE, as well as for the complications of anticoagulation and other definitive therapies. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Monitoring and follow-up' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Management of recurrence on therapy' and 'Monitoring and follow-up' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Charles Hales, MD, now deceased, who contributed to an earlier version of this topic review.