What are the common causes of provoked pulmonary embolism (PE)?

Causes of Provoked Pulmonary Embolism

Provoked PE occurs when identifiable, transient risk factors trigger venous thromboembolism, with the most common causes being recent surgery (especially major orthopedic procedures), active malignancy, prolonged immobilization, and trauma. 1

Strong Risk Factors (Odds Ratio >10)

The following conditions carry the highest risk for provoking PE and should be immediately recognized 2:

• Major orthopedic surgery, particularly hip or knee replacement—risk is highest in the first 2 postoperative weeks but remains elevated for 2-3 months 1
• Major trauma including lower limb fractures 1
• Hospitalization for heart failure or atrial fibrillation 2
• Myocardial infarction 1
• Spinal cord injury 1, 2
• Previous VTE (increases recurrence risk) 2

Moderate Risk Factors (Odds Ratio 2-9)

These conditions substantially increase PE risk 2:

• Active malignancy—particularly cancers of the uterus, pancreas, breast, stomach, and metastatic disease 1, 3
• Chemotherapy 1, 2
• Central venous catheters—though upper extremity clots rarely cause fatal PE 1
• Autoimmune diseases 2
• Hormone replacement therapy—risk varies widely depending on formulation used 1
• Arthroscopic knee surgery 2

Weak Risk Factors (Odds Ratio <2)

While individually less potent, these factors often combine to provoke PE 2:

• Prolonged immobilization (>1 week)—including bed rest and lower limb immobility from stroke 1
• Obesity 1
• Pregnancy and early puerperium—especially with operative delivery 1
• Oral contraceptives—current low-dose formulations carry lower risk than older preparations 1
• Advanced age (>40 years, with risk doubling each decade) 1
• Diabetes mellitus, arterial hypertension, hypercholesterolemia 1
• Long-distance air travel 1
• Varicose veins 2

Special Populations

Surgical Patients

The risk of VTE is highest during the first 2 postoperative weeks but remains elevated for 2-3 months after major surgery. 1 Non-orthopedic surgery carries lower risk than orthopedic procedures, and antithrombotic prophylaxis significantly reduces perioperative VTE incidence 1

Medical Inpatients

Over 80-90% of PE patients have identifiable predisposing factors 1. Common triggers in hospitalized medical patients include 1:

• Cardiorespiratory disorders (congestive heart failure, chronic lung disease)
• Acute infections 1
• Blood transfusion and erythropoiesis-stimulating agents 1

Pediatric Patients

In children, PE is usually associated with DVT and is rarely unprovoked. 1 Serious chronic medical conditions and central venous lines are the primary triggers 1

Important Clinical Considerations

Multiple risk factors dramatically increase PE risk through additive effects. 1 When assessing patients, recognize that:

• The majority of symptomatic DVT involves proximal clots, which lead to PE in 40-50% of cases, often without clinical manifestations 1
• Cardiovascular risk factors (smoking, obesity, hypercholesterolemia, hypertension, diabetes) may represent indirect associations mediated through coronary artery disease complications rather than direct PE triggers 1, 2
• Occult malignancy should be considered in patients presenting with unprovoked PE or recurrent PE 1
• Failure to rapidly achieve therapeutic anticoagulation levels independently predicts early recurrence 1

Common Pitfalls

Do not overlook temporary risk factors in patients who appear otherwise healthy—young women on oral contraceptives presenting with isolated pleuritic chest pain are very unlikely to have PE if respiratory rate is <20/min with normal chest radiograph 1, but the presence of additional risk factors changes this assessment dramatically.

Recognize that recurrence is more frequent after unprovoked VTE versus provoked events with temporary risk factors, particularly surgery. 1 This distinction critically impacts anticoagulation duration decisions.