eMedicine Specialties > Pulmonology > Pulmonary Embolism

Pulmonary Embolism

Author: Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St. Boniface General Hospital
Contributor Information and Disclosures

Updated: Jun 2, 2006

Introduction

Background

Pulmonary embolism (PE) is a common and potentially lethal disease; unfortunately, the diagnosis is often missed because patients with PE present with nonspecific signs and symptoms. If left untreated, approximately one third of patients who survive an initial PE subsequently die from a future embolic episode. Most patients succumb to PE within the first few hours of the event. In patients who survive, recurrent embolism and death can be prevented with prompt diagnosis and therapy.

The mortality and morbidity rates from venous thromboembolism are best described by Ken Moser in 2 words: substantial and unacceptable. In the 1940s, Bauer performed fundamental studies that led to the current understanding of the pathogenesis of deep vein thrombosis (DVT). Subsequently, Savitt and Gallagher performed autopsy-based studies of the prevalence of venous thromboembolism in patients who had lower extremity fractures and other risk factors for PE. The most important conceptual advance that occurred over the last several decades is that PE is not a disease; rather, it is a complication of DVT.

Virtually every physician who is involved in patient care (eg, internist, generalist, orthopedic surgeon, gynecologic surgeon, urologic surgeon, pulmonary subspecialist, cardiologist) encounters patients who are at risk of venous thromboembolism.

Pathophysiology

The pathophysiology of PE encompasses several aspects, as described below.

Natural history of venous thrombosis

In the 19th century, Verchow identified a triad of factors that lead to the pathogenesis of venous thrombosis: venous stasis, injury to the intima, and changes in the coagulation properties of the blood. Thrombosis usually originates as a platelet nidus in the region of venous valves located in the veins of the lower extremities. Further growth occurs by accretion of platelets and fibrin and progression to red fibrin thrombus, which may either break off and embolize or result in total occlusion of the vein. The endogenous thrombolytic system leads to partial dissolution; then, the thrombus becomes organized and is incorporated into the venous wall.

Natural history of pulmonary embolism

Pulmonary emboli usually arise from the thrombi originating in the deep venous system of the lower extremities; however, rarely they may originate in the pelvic, renal, or upper extremity veins and the right heart chambers. After traveling to the lung, large thrombi lodge at the bifurcation of the main pulmonary artery or the lobar branches and cause hemodynamic compromise. Smaller thrombi continue traveling distally, occluding a smaller vessel in the lung periphery. These are more likely to produce pleuritic chest pain by initiating an inflammatory response adjacent to the parietal pleura. Most pulmonary emboli are multiple, and the lower lobes are involved more commonly than the upper lobes.

Respiratory consequences

Acute respiratory consequences of PE include increased alveolar dead space, pneumoconstriction, hypoxemia, and hyperventilation. Later, 2 additional consequences may occur: regional loss of surfactant and pulmonary infarction. Arterial hypoxemia is a frequent but not universal finding in patients with acute embolism. The mechanisms of hypoxemia include ventilation-perfusion mismatch, intrapulmonary shunts, reduced cardiac output, and intracardiac shunt via patent foramen ovale. Pulmonary infarction is an uncommon consequence because of the bronchial arterial collateral circulation.

Hemodynamic consequences

PE reduces the cross-sectional area of the pulmonary vascular bed, resulting in an increment in pulmonary vascular resistance, which, in turn, increases the right ventricular afterload. If the afterload is increased severely, right ventricular failure may ensue. In addition, the humoral and reflex mechanisms contribute to the pulmonary arterial constriction. Prior poor cardiopulmonary status of the patient is an important factor leading to hemodynamic collapse. Following the initiation of anticoagulant therapy, the resolution of emboli occurs rapidly during the first 2 weeks of therapy. Significant long-term nonresolution of emboli causing pulmonary hypertension or cardiopulmonary symptoms is uncommon.

Frequency

United States

PE is present in 60-80% of patients with DVT, even though more than half the patients are asymptomatic. PE is the third most common cause of death in hospitalized patients, with at least 650,000 cases occurring annually. Autopsy studies have shown that approximately 60% of patients who died in the hospital had PE, and the diagnosis was missed in up to 70% of the cases. Prospective studies have demonstrated DVT in 10-13% of all medical patients placed on bed rest for 1 week, 29-33% of all patients in medical intensive care units, 20-26% of patients with pulmonary diseases who are given bed rest for 3 or more days, 27-33% of those admitted to a critical care unit after a myocardial infarction, and 48% of patients who are asymptomatic after a coronary artery bypass graft.

A 30-year, population-based study collated the cases of DVT or PE in women during pregnancy or during the postpartum period. The relative risk was 4.29, and the overall incidence of venous thromboembolism (absolute risk) was 199.7 per 100,000 woman-years. Among postpartum women, the annual incidence was 5 times higher than the pregnant women (511.2 vs 95.8 per 100,000 women). The incidence of DVT was 3 times higher than that of PE (151.8 vs 47.9 per 100,000 women). PE was relatively less common during pregnancy versus the postpartum period (10.6 vs 159.7 per 100,000 women) (Heit, 2005).

International

The incidence of PE may differ substantially from country to country; observed variation is likely due to differences in the accuracy of diagnosis rather than the disease incidence.

Mortality/Morbidity

• Unexpected death from a massive PE is second only to the sudden cardiac death. Autopsy studies of hospitalized patients have shown approximately 80% of these patients died from massive PE.
• Approximately 10% of patients who develop PE die within the first hour, and 30% die subsequently from recurrent embolism. Anticoagulant treatment decreases the mortality rate to less than 5%.
• The diagnosis of PE is missed in approximately 400,000 patients in the United States per year, approximately 100,000 deaths could be prevented with proper diagnosis and treatment.

Sex

• The risk of PE is increased in pregnancy and during the postpartum period; otherwise, sex is not a significant risk factor for PE.

Age

• In hospitalized elderly patients, PE is commonly missed and often is the cause of death.

Clinical

History

The presentation of pulmonary embolism (PE) may vary from a sudden onset of catastrophic hemodynamic collapse to gradually progressive dyspnea. The diagnosis of PE should be sought actively in patients with respiratory symptoms unexplained by an alternate diagnosis. The symptoms of PE are nonspecific; therefore, a high index of suspicion is required, particularly when a patient has risk factors, which include recent surgery, immobility, or a hypercoagulable state.

The presentation of patients with PE can be categorized into 4 classes based on the acuity and severity of pulmonary arterial occlusion. These categories are (1) massive PE, (2) acute pulmonary infarction, (3) acute embolism without infarction, and (4) multiple pulmonary emboli.

• Massive pulmonary embolism
  • Large emboli compromise sufficient pulmonary circulation to produce circulatory collapse and shock.
  • The patient has hypotension; appears weak, pale, sweaty, and oliguric; and develops impaired mentation.
• Acute pulmonary infarction
  • Approximately 10% of patients have peripheral occlusion of a pulmonary artery causing parenchymal infarction.
  • These patients present with acute onset of pleuritic chest pain, breathlessness, and hemoptysis.
  • Although the chest pain may be indistinguishable from ischemic myocardial pain, normal electrocardiogram findings and no response to nitroglycerine rules it out.
• Acute embolism without infarction: Patients have nonspecific symptoms of unexplained dyspnea and/or substernal discomfort.
• Multiple pulmonary emboli
  • This group consists of 2 subsets of patients.
  • The first subset has repeated documented episodes of pulmonary emboli over years, eventually presenting with signs and symptoms of pulmonary hypertension and cor pulmonale.
  • The second subset has no previously documented pulmonary emboli but have widespread obstruction of the pulmonary circulation with clot. They present with gradually progressive dyspnea, intermittent exertional chest pain, and, eventually, features of pulmonary hypertension and cor pulmonale.
• Most patients with PE have no obvious symptoms at presentation. In contrast, patients with symptomatic deep vein thrombosis (DVT) commonly have PE confirmed on diagnostic studies in the absence of pulmonary symptoms.
• The most common symptoms of PE in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study were dyspnea (73%), pleuritic chest pain (66%), cough (37%), and hemoptysis (13%).
• Patients with PE may present with atypical symptoms, where strong suspicion in a high-risk patient often leads to consideration of PE in the differential diagnosis. These symptoms include the following:
  • Seizures
  • Syncope
  • Abdominal pain
  • Fever
  • Productive cough
  • Wheezing
  • Decreasing level of consciousness
  • New onset of atrial fibrillation
• Pleuritic chest pain without other symptoms or risk factors may be a presentation of PE.

Physical

The physical examination is quite variable in PE and, for convenience, may be grouped into 4 categories as follows:

• Massive pulmonary embolism
  • These patients are in shock. They have systemic hypotension, poor perfusion to the extremities, tachycardia, and tachypnea.
  • Additionally, signs of pulmonary hypertension such as palpable impulse over second left interspace, loud P2, right ventricular S3 gallop, and a systolic murmur louder on inspiration at left sternal border (tricuspid regurgitation) may be present.
• Acute pulmonary infarction
  • These patients have decreased excursion of involved hemithorax, palpable or audible pleural friction rub, and even localized tenderness.
  • Signs of pleural effusion, such as dullness upon percussion and diminished breath sounds, may be present.
• Acute embolism without infarction
  • These patients have nonspecific physical signs that may easily be secondary to another disease process.
  • Tachypnea and tachycardia frequently are detected, pleuritic pain sometimes may be present, crackles may be heard in the area of embolization, and local wheeze may be heard rarely.
• Multiple pulmonary emboli or thrombi
  • Patients belonging to both the subsets in this category have physical signs of pulmonary hypertension and cor pulmonale.
  • Patients may have elevated jugular venous pressure, right ventricular heave, palpable impulse in the left second intercostal space, right ventricular S3 gallop, systolic murmur over the left sternal border that is louder during inspiration, hepatomegaly, ascites, and dependent pitting edema.
  • These findings are not specific for PE and require a high index of suspicion for pursuing appropriate diagnostic studies.
• The most common physical signs in the PIOPED study were as follows:
  • Tachypnea (70%)
  • Rales (51%)
  • Tachycardia (30%)
  • Fourth heart sound (24%)
  • Accentuated pulmonic component of the second heart sound (23%)
• Fever of less than 39°C may be present in 14% of patients; however, temperature higher than 39.5°C is not from PE.
• Chest wall tenderness upon palpation, without a history of trauma, may be the sole physical finding in rare cases.

Causes

The causes for PE are multifactorial and are not readily apparent in many cases. The following causes have been described in the literature:

• Venous stasis
  • Venous stasis leads to accumulation of platelets and thrombin in veins.
  • Increased viscosity may occur due to polycythemia and dehydration, immobility, raised venous pressure in cardiac failure, or compression of a vein by a tumor.
• Hypercoagulable states
  • The complex and delicate balance between coagulation and anticoagulation is altered by many diseases, by obesity, after surgery, or by trauma.
  • Concomitant hypercoagulability may be present in disease states where prolonged venous stasis or injury to veins occurs.
  • Hypercoagulable states may be acquired or congenital. Factor V Leiden mutation causing resistance to activated protein C is the most common risk factor. Factor V Leiden mutation is present in up to 5% of the normal population and is the most common cause of familial thromboembolism.
  • Primary or acquired deficiencies in protein C, protein S, and antithrombin III are other risk factors. The deficiency of these natural anticoagulants is responsible for 10% of venous thrombosis in younger people
• Immobilization
  • Immobilization leads to local venous stasis by accumulation of clotting factors and fibrin, and a thrombus is synthesized.
  • The risk of PE increases with prolonged bed rest or immobilization of a limb with plaster.
  • Paralysis increases the risk.
• Surgery and trauma
  • Both surgical and accidental trauma predispose patients to venous thromboembolism by activating clotting factors and causing immobility.
  • Fractures of the femur and tibia are associated with the highest risk, followed by pelvic, spinal, and other fractures.
  • Severe burns carry a high risk of DVT or PE.
  • A recent study by Greets in 1994 indicated that major trauma was associated with a 58% incidence rate of DVT, 18% of these were in proximal veins.
  • PE may account for 15% of all postoperative deaths. Leg amputations and hip, pelvic, and spinal surgery are associated with the highest risk.
• Pregnancy
  • The incidence of thromboembolic disease in pregnancy has been reported to range from 1 case in 200 deliveries to 1 case in 1400 deliveries.
  • Fatal events may occur rarely, 1-2 cases per 100,000 pregnancies.
  • The mechanism of DVT is venous stasis, decreasing fibrinolytic activity, and increased procoagulant factors.
• Oral contraceptives and estrogen replacement
  • Estrogen-containing birth control pills have increased the occurrence of venous thromboembolism in healthy women.
  • The risk is proportional to the estrogen content and is increased in postmenopausal women on hormonal replacement therapy.
  • The relative risk is 3-fold, but the absolute risk is 20-30 cases per 100,000 persons per year.
• Malignancy
  • Malignancy has been identified in 17% of patients with venous thromboembolism.
  • The neoplasms most commonly associated with PE, in descending order of frequency, are pancreatic carcinoma; bronchogenic carcinoma; and carcinoma of the genitourinary tract, colon, stomach, and breast.
• Other recognized risk factors include the following:
  • Stroke
  • Indwelling venous catheters
  • Previous history of venous thromboembolism
  • Congestive heart failure
  • Fractures of the long bone
  • Obesity
  • Pregnancy
  • Varicose veins
  • Inflammatory bowel disease

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