Does chemotherapy increase the risk of pulmonary embolism (PE)?

Chemotherapy Significantly Increases the Risk of Pulmonary Embolism

Yes, chemotherapy substantially increases the risk of pulmonary embolism (PE) and venous thromboembolism (VTE), with cancer patients receiving chemotherapy having a 7-fold increased risk compared to cancer patients not receiving chemotherapy. 1

Magnitude of Risk

The evidence from major oncology guidelines demonstrates a clear and substantial risk increase:

• Cancer patients on chemotherapy have a 6.5-fold increased risk of VTE compared to the general population 1
• The 7-fold risk elevation is specifically attributable to chemotherapy administration when comparing cancer patients receiving versus not receiving chemotherapy 1
• Overall VTE incidence ranges from 7.3% at 3.5 months to 13.5% at 12 months after starting chemotherapy in real-world cohorts 2
• Asymptomatic PE occurs in approximately 15% of lung cancer patients receiving chemotherapy, indicating significant underdiagnosis 3

Mechanisms of Chemotherapy-Induced Thrombosis

The European Society for Medical Oncology (ESMO) identifies four distinct mechanisms by which cytotoxic chemotherapy increases PE risk 1:

• Acute vascular endothelial damage from direct toxic effects
• Chronic endothelial injury leading to prothrombotic state
• Depletion of natural anticoagulants (protein C, protein S, antithrombin III)
• Platelet activation promoting clot formation

High-Risk Chemotherapy Regimens

Certain chemotherapy agents carry particularly elevated thrombotic risk 1:

• Cisplatin-based regimens increase VTE risk by 1.67-fold through endothelial injury, platelet activation, and renal damage 4
• Bevacizumab with chemotherapy increases VTE by 33%, with overall VTE incidence of 11.9% (any grade) and 6.3% (high-grade) 1
• Thalidomide plus doxorubicin in multiple myeloma carries up to 34% VTE rate 1
• Lenalidomide with high-dose dexamethasone in relapsed myeloma shows similarly elevated rates 1

Risk Stratification for Chemotherapy Patients

The ESMO guidelines provide a validated predictive model for chemotherapy-associated VTE 1:

Cancer site risk scores:

• Very high risk (stomach, pancreas): 2 points 1
• High risk (lung, lymphoma, gynecologic, bladder, testicular): 1 point 1

Laboratory risk factors (1 point each): 1

• Platelet count ≥350,000/µL
• Hemoglobin <10 g/dL or erythropoiesis-stimulating agent use
• Leukocyte count >11,000/µL

Patient factors:

• BMI ≥35 kg/m²: 1 point 1

Risk categories: 1

• Low risk (score 0): 0.5% VTE rate
• Intermediate risk (score 1-2): 2% VTE rate
• High risk (score ≥3): 7% VTE rate

Clinical Impact and Mortality

The development of PE during chemotherapy has severe prognostic implications 1:

• VTE increases mortality risk 3-fold in cancer patients 1
• 30-day risk of death, shock, or recurrent PE triples when cancer patients develop VTE 1
• 3-month all-cause mortality reaches 26.4% in cancer patients with VTE versus 4.1% without 1
• Major bleeding risk increases to 11% at 3.5 months and 19.8% at 12 months in chemotherapy patients who develop VTE 2

Common Pitfalls

Underestimation of asymptomatic PE: Most oncologists underestimate VTE prevalence, and asymptomatic PE is frequently missed on staging CT scans 1, 3. Incidental PE found on imaging should be treated identically to symptomatic PE 1.

Central venous catheter contribution: The combination of chemotherapy plus central venous catheters creates additive thrombotic risk, particularly with cisplatin-based regimens 4, 5.

Timing of highest risk: VTE risk peaks in the first few months after cancer diagnosis and during early chemotherapy cycles 1, 3, requiring heightened vigilance during this period.

Antiangiogenic agent synergy: The thrombogenic effects of bevacizumab, thalidomide, and lenalidomide are amplified when combined with chemotherapy and corticosteroids 1, necessitating consideration of prophylaxis in high-risk scenarios.