What are the risk factors for pulmonary embolism?

Risk Factors for Pulmonary Embolism

Pulmonary embolism risk factors are stratified by strength: strong risk factors (OR >10) include lower limb fractures, hip/knee replacement, major trauma, myocardial infarction within 3 months, previous VTE, and spinal cord injury; moderate risk factors (OR 2-9) include active malignancy, chemotherapy, acute infections (pneumonia, UTI, HIV), autoimmune diseases, central venous catheters, and hormonal therapies; weak risk factors (OR <2) include bed rest >3 days, diabetes, hypertension, and obesity. 1

Strong Risk Factors (Odds Ratio >10)

The highest-risk conditions for PE development include:

• Major orthopedic surgery, particularly hip or knee replacement, which carries the strongest association with PE 1
• Lower limb fractures and major trauma, which dramatically increase thrombotic risk through both immobilization and endothelial injury 1
• Spinal cord injury, which combines profound immobilization with neurogenic hypercoagulability 1
• Recent myocardial infarction (within 3 months), reflecting the shared pathophysiology of inflammation, hypercoagulability, and endothelial injury between venous and arterial thrombosis 1
• Previous venous thromboembolism, as recurrence risk remains substantially elevated even after initial treatment 1

These conditions warrant aggressive thromboprophylaxis in hospitalized patients. 2

Moderate Risk Factors (Odds Ratio 2-9)

Malignancy

• Active cancer, especially pancreatic, hematologic, lung, gastric, brain, uterine, breast, and stomach malignancies, significantly increases PE risk 1
• Metastatic disease carries the highest cancer-associated PE risk 1
• Chemotherapy independently increases thrombotic risk beyond the malignancy itself 1
• The association between PE and occult malignancy is significant, with many patients diagnosed with PE later found to have previously undetected cancer 2

Acute Medical Conditions

• Acute infections, specifically pneumonia, urinary tract infection, and HIV, increase PE risk through inflammatory mechanisms 1
• Cardiorespiratory disorders, particularly congestive heart failure, congenital heart disease, and irreversible airways disease, contribute to venous stasis 3, 2
• Autoimmune diseases create a pro-thrombotic inflammatory state 1

Iatrogenic and Device-Related

• Central venous catheters cause endothelial injury and provide a nidus for thrombus formation 1
• Postoperative intensive care combines multiple risk factors including immobility and inflammation 3

Hormonal Factors

• Combined oral contraceptives increase VTE risk 2-6 fold, with third-generation agents (containing desogestrel or gestodene) carrying higher risk than second-generation formulations 3, 4
• Hormone replacement therapy and other estrogen therapies increase PE risk, particularly in combination with other risk factors 2, 1
• Pregnancy and the postpartum period increase risk 5-fold compared to non-pregnant women of similar age, with 75% of DVT occurring antepartum and 66% of PE occurring postpartum 3
• Pre-eclampsia, cesarean section, and multiple births further amplify pregnancy-related risk 2

Weak Risk Factors (Odds Ratio <2)

• Prolonged bed rest (>3 days) or immobilization, even short-term (one week), predisposes to VTE through venous stasis 3, 1
• Obesity has been confirmed as an independent risk factor 2, 1
• Diabetes mellitus and arterial hypertension carry modest associations 1
• Advanced age, particularly over 40 years, shows exponentially increasing PE risk, though this may reflect higher frequency of comorbidities rather than age itself 3, 2

Inherited Thrombophilia

• Inherited or acquired thrombophilia is found in 25-50% of patients with PE 2
• Factor V Leiden mutation increases PE risk 3-5 fold alone, but in combination with estrogen therapy, this risk rises to 35-fold 2
• Prothrombin 20210A mutation, antithrombin III deficiency, protein C and S deficiencies, and hyperhomocysteinemia are other important genetic defects 3
• Thrombophilia should be considered in patients with documented unexplained thrombotic episodes below age 40, recurrent DVT or PE, and positive family history 3

Clinical Implications and Common Pitfalls

All patients with possible PE should have clinical probability assessed and documented using validated risk scores (Wells, Geneva), as the presence of risk factors significantly influences pre-test probability and guides diagnostic strategies. 2, 1

Key Pitfalls to Avoid:

• Not recognizing that PE risk increases exponentially with age rather than linearly 2
• Failing to consider thrombophilia in young patients with unexplained thrombotic episodes 2
• Overlooking the synergistic effect of multiple risk factors, particularly the 35-fold increase when Factor V Leiden combines with estrogen therapy 2
• Underestimating immobility as a risk factor, even short-term immobilization of one week can predispose to VTE 3, 2
• Overlooking that almost one in two cases of PE occur in the absence of a classical predisposing factor, requiring high clinical suspicion even without obvious risk factors 3