Venous Thromboembolism

2.1.1 Overview of Venous Thromboembolism

VTE refers to all forms of pathologic thrombosis occurring within the venous

circulation, represents a spectrum from simple superficial thrombophlebitis to fatal

pulmonary embolism. Most venous thrombosis occurs at the deep veins of the lower

extremities, giving rise to deep vein thrombosis (DVT). They also can occur in other

parts of body, including the veins of the upper extremities, pelvis, abdomen, and

cerebral venous sinuses. Pulmonary embolism (PE) is the most life-threatening

manifestation of VTE, which occurs when a clot dislodges from the site of formation

and embolizes into pulmonary arteries. Death from PE can occur within minutes after

the onset of symptoms, before effective treatment is given.^19,20

2.1.2 Epidemiology of Venous Thromboembolism

The actual incidence of VTE is unknown because the disease is often clinically

silent. The annual incidence rate of VTE is reported to be 104-183 events per 100,000

persons in the Caucasian populations (Table 2.1).^21-25 The annual incidence of VTE

increases markedly with age, from less than 5 cases per 100,000 persons under 15

year-old to 149 events per 100,000 persons over the age of 80.²¹

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The prevalence of VTE varies among different ethnic cohorts. Compared to

Caucasian populations, the incidence of VTE is significantly higher among African-

American and significantly lower among Asian populations.^22,26,27 Among Asian

populations, the estimated annual incidence of VTE is 14-57 per 100,000 persons (Table

2.1).^8,10,28,29 The incidence ranges from 2.5 events per 100,000 person-years in those

younger than 30 years to 100 events per 100,000 person-years in those aged over 80

years.¹⁰ Although the annual incidence of VTE among Asian populations has been

perceived to be lower than Caucasian populations, it appears to be rapidly increasing.^8,30

Along with rapid aging of the population, VTE is a major healthcare problem which

causing significant mortality, morbidity and healthcare resource expenditure in our

aging society.

Table 2.1 Incidence of venous thromboembolism reported in different populations Incidence per 100,000

Location Study design VTE DVT PE

America

Minnesota (Silverstein et al. 1998)²¹ California (only Caucasian)²² (White et al. 2005)

Worcester (Spencer et al. 2009)³¹

Population-based study

French (Oger et al. 2000)²⁴ Norway (Naess et al. 2007)²⁵

Population-based study

Hong Kong (Cheuk et al. 2004)²⁸ Singapore (Molina et al. 2009)²⁹ Taiwan (Lee et al. 2010)¹⁰ Korea (Jang et al. 2011)⁸

Population-based study

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2.1.3 Risk Factors for Venous Thromboembolism

VTE is a multifactorial condition involving genetic and both constant and transient

acquired risk factors. In 1884, Virchow’s triad first described three primary factors

contribute to the formation of thrombosis: abnormalities in blood flow (venous stasis),

abnormalities in blood constituents (hypercoagulability), and abnormalities in the vessel

wall (vascular endothelial injury). Risk factors for VTE, include increasing age,

malignancy, prolonged immobility, major surgery, major trauma, prior VTE, chronic

heart failure, and inherited or acquired thrombophilia, alter one or more of the

components of the triad (Table 2.2).³² There is convincing evidence that the risk of VTE

increases in proportion to the number of predisposing factors.^32,33

Compared with residents in the community, hospitalization without surgery or

nursing home confinement is associated with 8-folds increased risk of VTE.³⁴

Hospitalization and nursing home residence together account for almost 60% of incident

VTE events occurring in the community, with hospitalization for medical illness and

hospitalization for surgery accounted for 22% and 24% of VTE, respectively.²

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Table 2.2 Risk factors for venous thromboembolism Strong risk factors (odd ratio > 10)

Fracture (hip or leg) Hip or knee replacement Major general surgery Major trauma

Spinal cord injury

Moderate risk factors (odd ratio 2-9) Arthroscopic knee surgery

Central venous lines Chemotherapy

Congestive heart or respiratory failure Hormone replacement therapy

Weak risk factors (odd ratio < 2) Bed rest > 3 days

Immobility due to sitting (e.g. prolonged car or air travel) Increasing age

Laparoscopic surgery (e.g. cholecystectomy) Obesity

Pregnancy (antepartum) Varicose veins

Adapted from Anderson FA, Jr., Spencer FA. Risk factors for venous thromboembolism.

Circulation 2003;107:I9-16.

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2.1.4 Complications of Venous Thromboembolism

VTE is an important worldwide healthcare burden associated with significant

morbidity and mortality. It is reported to be the third common cardiovascular causes of

death after myocardial infarction and stroke.³⁵ The 1-week survival rate after a PE is

only 71%, and almost 25% of all cases of PE essentially present as sudden death.³⁶ In

USA, 100,000-300,000 VTE-related deaths occur every year and PE had been declared

to be the most common preventable cause of hospital death and the significant target to

improve patient safety in hospitals.³⁷

Recurrence of VTE is common. Despite anticoagulant therapy, about 30% of

patients develop recurrent VTE within the next ten years, with the highest recurrence

rate within the first year after their first VTE event.^38,39 Men have a higher rate of

recurrence than women (relative risk of recurrent VTE: 1.6).^40,41 In addition, survivors

of VTE always suffer from long-term complications, including post-thrombotic

syndrome and chronic thrombotic pulmonary hypertension. One-third to one-half of

patients with lower extremity DVT develop post-thrombotic syndrome during 20 years

of follow-up, characterized by pain and swelling, and in severe cases with venous

ulceration. These conditions can be disabling for patients and have great impact on

healthcare costs. Subsets of VTE patients require long-term anticoagulation to prevent

additional clots, which also decreases their quality of life and places them at an

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increased risk for adverse bleeding episodes.^37,38

2.1.5 Clinical Presentations of Venous Thromboembolism

The signs and symptoms of VTE are nonspecific. Furthermore, many patients with

VTE were asymptomatic. A leg DVT commonly presents with pain, erythema, and

swelling of the affected limb. Physical examination may show palpable cord, warmth,

and unilateral edema.^42,43 Patients with upper extremity or neck DVT often complain

with upper extremity or head or neck swelling, erythema, and/or discomfort.⁴⁴

Symptoms associated with PE depend on the degree of vascular obstruction, the

magnitude of inflammatory response, and the patient’s cardio-pulmonary reserve.

Patients may present with dyspnea, hypoxemia, tachycardia, pleuritic chest pain,

hemoptysis or even collapse with shock or pulseless electrical activity cardiac arrest.^20,43

2.1.6 Diagnosis of Venous Thromboembolism

Duplex ultrasonography remains the test of choice in the investigation and

diagnosis of clinically suspected DVT. Although ultrasound is highly sensitive for the

detection of proximal DVT, it is less accurate for isolated DVT of the calf. The ideal

method, invasive venography, is used when a definitive answer is required. Newer

image modalities such as magnetic resonance venography and computerized

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tomography (CT) scan can detect thrombosis of vessels proximal to the inguinal

ligament and intra-abdominal vessels. Another advantage of magnetic resonance

venography and CT scan is their ability to provide information about surrounding

structures that may lead to alternative diagnosis.^20,42-44

Gold standard for the diagnosis of PE is pulmonary angiography, but it is an

invasive procedure that involves injection of contrast dye into pulmonary artery and

associated with 0.5% of mortality. Nowadays, CT scan has become the most commonly

used imaging test to diagnose PE. Before CT scan, ventilation-perfusion (V/Q) scan was

the first-line imaging modality of PE. Spiral CT scan can detect emboli in the

pulmonary arteries whereas V/Q scan measures the distribution of blood and air flow in

the lungs.^20,42,43

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