Pulmonary embolism (PE) is a serious and potentially life-threatening condition that affects hundreds of thousands of people annually. It occurs when a blockage in the lung's arteries disrupts blood flow and oxygen exchange, often originating from blood clots formed elsewhere in the body1 . Understanding the various causes and risk factors of PE is essential for prevention, early diagnosis, and effective treatment2 .
Blood Clot Formation
The most common cause of pulmonary embolism is the formation of blood clots (thrombi) that travel to the lungs, primarily originating from deep veins in the legs or other parts of the body3 . This condition is known as deep vein thrombosis (DVT) and is the leading source of pulmonary emboli2 . The embolization of these thrombi to the pulmonary arteries causes obstruction of blood flow, which can lead to lung tissue damage and strain on the heart4 .
Several factors contribute to the formation of these clots, often described by Virchow’s triad: venous stasis (slow blood flow), endothelial injury (damage to the blood vessel lining), and hypercoagulability (increased tendency to clot) 5. Key risk factors include:
- Injury or trauma to veins, including surgery, which damages the vessel walls and promotes clot formation2 .
- Prolonged immobility or venous stasis, such as extended bed rest or long travel, which slows blood flow and encourages clotting2 .
- Hormonal influences, including pregnancy and estrogen therapy, which increase clotting risk2 .
- Chronic illnesses like cancer and inflammatory diseases that predispose individuals to thrombosis2 .
Prompt recognition and treatment of DVT are critical to prevent pulmonary embolism. Anticoagulant medications are the mainstay of therapy to reduce clot formation and embolization1 .
Air Embolism Causes
Air embolism is a less common cause of pulmonary embolism, occurring when air enters the venous system and obstructs pulmonary circulation6 . This can happen accidentally during medical procedures or trauma. Common causes include:
- Iatrogenic events such as central venous catheter placement and manipulation6 .
- Major surgeries, particularly cardiac and neurosurgical operations, which may introduce air into the bloodstream6 .
- Endoscopic procedures and contrast angiography, where air can be inadvertently introduced6 .
- Lung biopsies that allow air entry into pulmonary veins6 .
- Chest trauma disrupting vascular integrity6 .
- Decompression sickness in divers, leading to arterial gas embolism due to rapid ascent6 .
Although rare, air embolism is a medical emergency requiring immediate recognition and management to prevent severe cardiopulmonary complications7 .
Fat Embolism Sources
Fat embolism syndrome results from fat globules entering the circulation and lodging in pulmonary vessels, causing obstruction and inflammation2 . This condition is most often associated with trauma and orthopedic procedures. Key sources include:
- Long bone fractures, especially of the femur or pelvis, which release fat from bone marrow into the bloodstream2 .
- Surgical manipulation of bones during orthopedic operations, which can dislodge fat globules2 .
- Bone marrow necrosis due to hematologic diseases or treatments, which may precipitate fat embolism2 .
Fat embolism typically presents shortly after trauma or surgery and requires supportive care and monitoring2 .
Amniotic Fluid Embolism
Amniotic fluid embolism (AFE) is a rare but severe obstetric emergency occurring around the time of delivery8 . It involves the entry of amniotic fluid into the maternal circulation, triggering a sudden cardiopulmonary collapse8 . Initially thought to be caused by mechanical obstruction of pulmonary vessels, current understanding favors an immunologic reaction as the primary mechanism8 . The precise pathophysiology remains incompletely understood and is an area of ongoing research8 .
AFE is life-threatening and requires rapid diagnosis and intensive supportive treatment8 .
Tumor Embolism Origins
Tumor embolism occurs when malignant cells enter the circulation and obstruct pulmonary vessels8 . Certain adenocarcinomas have a higher propensity to cause tumor embolism in the lungs. Malignancies commonly associated with increased pulmonary embolism risk include lung, breast, and gastrointestinal cancers8 . Tumor emboli are rare compared to thrombotic causes but represent an important consideration in cancer patients presenting with respiratory symptoms8 .
Septic Embolism Causes
Septic emboli are infected clots or tissue fragments that embolize to the lungs, causing both infection and vascular obstruction8 . They often originate from infected thrombi in deep veins or from right-sided heart valve infections. Risk factors include intravenous drug use and infective endocarditis8 . Septic pulmonary embolism requires antimicrobial therapy alongside management of the embolic obstruction8 .
Foreign Body Embolism
Foreign body embolism results from nonbiological particles introduced into the bloodstream that obstruct pulmonary vessels8 . Common sources include:
- Intravenous drug users injecting insoluble substances8 .
- Medical device coatings or debris introduced during interventions8 .
Though rare, foreign body embolism can cause significant pulmonary vascular obstruction and inflammation8 .
Is Pulmonary Embolism Hereditary?
A family history of venous thromboembolism (VTE) is a recognized risk factor for pulmonary embolism3 . Inherited thrombophilias, caused by gene mutations, increase the risk of abnormal blood clotting and subsequent PE3 . These genetic conditions disrupt the balance of coagulation and anticoagulation, predisposing individuals to thrombosis3 .
Key inherited thrombophilias include:
- Factor V Leiden mutation, which causes resistance to activated protein C and increases clot risk3 .
- Antithrombin deficiency, impairing natural anticoagulation3 .
- Protein C deficiency, reducing anticoagulant activity3 .
- Protein S deficiency, impairing the protein C anticoagulant pathway3 .
Inherited thrombophilia alone increases risk but usually requires additional acquired factors to cause PE. The combination of genetic and environmental risk factors synergistically raises the likelihood of pulmonary embolism3 .
Pulmonary Embolism Risk Groups
Pulmonary embolism can affect individuals across all demographics, but risk varies based on age, sex, ethnicity, and other factors3 . Non-modifiable risk factors include:
- Older age, particularly over 40, due to age-related changes in coagulation and venous function3 .
- Female sex, with increased risk related to hormonal factors such as pregnancy and contraceptive use3 .
- Ethnic disparities, with higher incidence and mortality among Black populations, partly due to healthcare inequities and implicit bias3 .
Addressing healthcare disparities is essential to reduce mortality differences and improve outcomes in high-risk groups3 .
Key Risk Factors
Medical History
Several medical conditions and histories increase the risk of pulmonary embolism:
- Previous venous thromboembolism, which strongly predicts recurrence3 .
- Cancer and cancer therapies, especially brain, ovary, pancreas, colon, stomach, lung, and kidney cancers3 .
- Heart diseases such as heart failure, myocardial infarction, and stroke3 .
- Autoimmune and inflammatory diseases, including lupus and inflammatory bowel disease3 .
- COVID-19 infection, particularly severe cases, increases PE risk9 .
Geography
Seasonal and regional variations influence pulmonary embolism incidence and mortality. The winter season is associated with higher PE occurrence and deaths, likely due to reduced mobility, cold-induced vasoconstriction, and respiratory infections3 . Environmental factors such as air pollution also correlate with increased venous thromboembolism risk3 .
Lifestyle
Behavioral factors play a significant role in PE risk:
- Prolonged immobility, such as extended bed rest or long travel, promotes venous stasis and clot formation2 .
- Tobacco use increases the risk of blood clots, especially in combination with other risk factors3 .
- Obesity contributes to increased clotting risk3 .
- Regular physical activity and smoking cessation are advised to lower PE risk3 .
Medications
Certain medications influence clotting and PE risk:
- Hormonal therapies, including estrogen-containing birth control pills and hormone replacement therapy, increase clotting factors and PE risk2 .
- Chemotherapy agents can elevate thrombosis risk in cancer patients3 .
“Evaluation of pulmonary embolism includes assessment of clinical probability and, if indicated, d-dimer testing. Most patients with low-risk pulmonary embolism can be treated with oral anticoagulants.”
— Susan R. Kahn, McGill University10
Summary and Key Points
Pulmonary embolism is a complex condition primarily caused by blood clots originating in deep veins, with multiple other embolic sources contributing less commonly. Risk factors encompass genetic predispositions, medical history, lifestyle, and environmental influences. Early recognition and management are critical to reduce morbidity and mortality.
Key takeaways include:
- Deep vein thrombosis is the leading cause of pulmonary embolism, with venous stasis, endothelial injury, and hypercoagulability as central mechanisms3 .
- Non-thrombotic emboli such as air, fat, amniotic fluid, tumor cells, septic emboli, and foreign bodies are less common but important causes2 .
- Inherited thrombophilias significantly increase PE risk but often require additional acquired factors to trigger embolism3 .
- Older age, female sex, and Black ethnicity are associated with higher PE risk, highlighting the need for targeted prevention and equity in healthcare3 .
- Lifestyle modifications, including physical activity and smoking cessation, alongside careful management of medical conditions and medications, can reduce PE risk3 .
