What is Venous Thromboembolic Disease?
Venous thromboembolic disease (VTE) is a life-threatening condition characterized by blood clot formation in the venous system, encompassing deep vein thrombosis (DVT), pulmonary embolism (PE), superficial vein thrombosis (SVT), and thrombosis in other vascular territories including the portal vein, mesenteric vein, inferior vena cava, superior vena cava, and pelvis. 1
Core Pathophysiology
VTE represents a blood clot that most frequently originates in the deep veins of the legs or pelvis (DVT), which can break free from the vein wall and travel to the lungs, blocking pulmonary blood supply (PE), potentially causing death. 1
The underlying mechanisms follow Virchow's Triad, which includes three fundamental elements:
- Venous stasis (blood flow slowing or pooling) 2
- Vascular injury (damage to blood vessel walls) 2
- Hypercoagulability (increased blood clotting tendency) 2
Clinical Significance and Mortality Impact
VTE is a leading cause of morbidity and mortality in hospitalized patients, with approximately 500,000 VTE events occurring annually in the USA and over 600,000 DVT events plus 400,000 PE events across the European Union. 1
The mortality burden is substantial:
- An estimated 28,726 hospitalized patients diagnosed with VTE die annually in the USA 1
- Three-quarters of 500,000 VTE-related deaths in Europe were from hospital-acquired VTE 1
- In cancer patients specifically, VTE increases the likelihood of death by 2- to 6-fold 1
- VTE affects nearly 10 million people worldwide annually 3
Hospital-Related VTE Events
52% of annually reported VTE in the USA are related to current or recent hospitalization, with 25% occurring during inpatient stay and 75% happening within 92 days of hospital discharge (median 19.5 days). 1
Anatomical Classification
The NCCN defines VTE broadly across multiple vascular territories 1:
Deep Vein Thrombosis (DVT) categories:
- Upper extremity and superior vena cava 1
- Lower extremity (including inferior vena cava, pelvis, iliac, femoral, and popliteal veins) 1
- Distal lower extremity (calf veins) 1
- Splanchnic vasculature 1
- Central venous access device (CVAD)-related DVT 1
Other VTE manifestations:
Risk Factor Categories
Systemic Risk Factors
- Acquired thrombophilias (antiphospholipid syndrome) 4
- Pregnancy and postpartum state 4
- Hormonal contraceptives and hormone replacement therapy 4
- Malignant diseases (10% of patients with idiopathic VTE develop cancer later) 4
- Advanced age 1
- Obesity 1
- Critical illness (ICU/CCU stays increase VTE risk 1.65-fold) 5
Local Risk Factors
- Compression by solid tumors or cysts 4
- Abdominal operations and infections 4
- Membranous obstruction of the IVC (particularly in Asian countries) 4
- Behçet's disease (particularly in Asia) 4
Cancer-Specific Considerations
In cancer patients, VTE pathophysiology includes hypercoagulability from procoagulants like tissue factor expressed by cancer cells, vessel wall damage, and vessel stasis from direct tumor compression. 1 Additional risk factors include chemotherapeutic regimens, surgical procedures, and prolonged immobilization. 1
Clinical Presentation Spectrum
VTE manifestations range from asymptomatic (up to 20% of IVC thrombosis cases, particularly with large collaterals) to sudden death as the presenting manifestation of PE. 4, 6
Common pitfall: SVT is more likely to be symptomatic than DVT, presenting with pain, tenderness, erythema, and palpable cord, yet approximately 20-40% of patients with SVT have concurrent DVT that requires ultrasound evaluation. 7
Chronic Complications
Impaired thrombus resolution leads to two major chronic complications: postthrombotic syndrome (PTS) occurring in up to 50% of patients after symptomatic DVT, and chronic thromboembolic pulmonary hypertension (CTEPH). 8 These complications are associated with substantial morbidity, high healthcare expenses, and reported death rates of up to 40% at 10 years. 8