What is the primary problem in Venous Thromboembolism (VTE)?

The Primary Problem in Venous Thromboembolism

The primary problem in VTE is that it represents a major cause of morbidity and mortality, with blood clots forming in deep veins (DVT) or traveling to the lungs (PE), leading to serious complications including death, recurrent thrombosis, and chronic debilitating sequelae. 1

Core Pathophysiology

VTE encompasses two main clinical manifestations that share a common underlying pathologic process:

• Deep vein thrombosis (DVT) occurs when blood clots form in the deep veins, most commonly in the legs, pelvis, or upper extremities 1
• Pulmonary embolism (PE) develops when thrombi break free and travel to the pulmonary vasculature, potentially causing fatal obstruction 1, 2

The fundamental pathophysiologic triad driving VTE includes hypercoagulability, vessel wall damage, and venous stasis 1. In cancer patients specifically, tumor cells express procoagulants such as tissue factor that directly activate the coagulation cascade 1.

Magnitude of the Clinical Problem

Incidence and Prevalence

• The annual incidence in the general Western population is approximately 1.0 per 1000 for DVT and 0.5 per 1000 for PE 1
• In the United States, VTE accounts for 200,000 to 300,000 hospitalizations annually 1
• Approximately 500,000 VTE events occur annually in the USA, with an estimated 28,726 hospitalized patients dying from VTE each year 1

Mortality Impact

• Between 5% and 10% of all in-hospital deaths are directly caused by PE 1
• In autopsy studies, more than 70% of major PEs had been missed by clinicians during life 1
• The prevalence of unsuspected PE at autopsy ranges from 3% to 8% 1
• Patients with untreated PE face a 26% risk of fatal recurrent embolism and another 26% risk of nonfatal recurrence 1

Special High-Risk Populations

Cancer Patients

Cancer dramatically amplifies VTE risk and worsens outcomes:

• The 2-year cumulative incidence of VTE in cancer patients ranges from 0.8% to 8% 1
• Cancer patients have a 7-fold increased risk of VTE while receiving chemotherapy compared to non-cancer patients 1
• Among hospitalized cancer patients, 5.4% develop VTE, with rates increasing 36% from 1995 to 2002 1
• Cancer patients have a 3-fold higher risk of recurrent VTE compared to patients without malignancy 1
• The probability of readmission for recurrent VTE within 183 days is 22% for cancer patients versus 6.5% for those without cancer 1
• Patients with metastatic disease have a 4-13 times higher VTE rate compared to those with localized disease 1

Surgical and Hospitalized Patients

• The frequency of DVT varies by surgical procedure: 5% after herniorrhaphy, 15-30% after major abdominal surgery, and 50-75% after hip fracture surgery 1
• Hospitalized cancer patients are at even higher risk, with VTE development increasing both morbidity and mortality 1
• Most hospitalized medical patients have at least one risk factor for VTE, and this risk persists for several weeks after discharge 1

Consequences and Complications

Acute Complications

• Massive PE presents with shock and/or hypotension (systolic blood pressure <90 mmHg or pressure drop of 40 mmHg for >15 minutes) 1
• Fatal PE risk is 3-fold greater in cancer patients undergoing surgery compared to non-cancer patients undergoing similar procedures 1
• VTE diagnosis is associated with a 2-fold increase in in-hospital mortality (odds ratio 2.01,95% CI 1.83-2.22) 1

Chronic Complications

• Post-thrombotic syndrome (PTS) develops in up to 50% of patients after symptomatic DVT 3
• Chronic thromboembolic pulmonary hypertension (CTEPH) occurs in a small but significant number of patients after PE 3
• These chronic complications are associated with substantial morbidity, high healthcare expenses, and significant adverse impact on long-term quality of life 3
• Impaired thrombus resolution is the common denominator behind both PTS and CTEPH 3

Risk Factors

Primary (Congenital) Risk Factors

The most common genetic defects include 1:

• Factor V Leiden mutation (causing activated protein C resistance in 90% of cases)
• Prothrombin 20210A mutation
• Antithrombin III deficiency
• Protein C and S deficiencies
• Hyperhomocysteinemia

Secondary (Acquired) Risk Factors

Major secondary risk factors include 1:

• Age >60-65 years
• Active malignancy and chemotherapy
• Recent surgery or trauma
• Immobilization (even short-term, as brief as one week)
• Acute infections
• Stroke with paralysis
• Critical illness
• Previous VTE history
• Renal failure
• Thrombocytopenia

Common Pitfall

Almost one in two cases of PE and DVT occur in the absence of a classical predisposing factor, making risk assessment challenging 1. This underscores the importance of maintaining clinical suspicion even when obvious risk factors are not present.

The Recurrence Problem

VTE is characterized by high recurrence rates:

• The risk of recurrent VTE is greatest in the first few months after diagnosis and can persist for many years 1
• Cancer patients face a 3-fold higher recurrence risk compared to non-cancer patients 1
• Death rates reach up to 40% at 10 years following VTE 3