Table Of ContentDeep Vein Thrombosis & Pulmonary Embolism
Deborah Nicolls Barbeau
BACKGROUND
Venous thromboembolism (VTE) consists of 2 related conditions: 1) deep vein thrombosis (DVT) and 2)
pulmonary embolism (PE). DVT occurs when a deep vein is partially or completely blocked by a blood clot,
most commonly in the legs. The clot may break off and travel to the vessels in the lung, causing a life-
threatening PE.
VTE associated with air travel was first described in the early 1950s. Previous studies have shown a 2- to 4-fold
increased risk of VTE after air travel. In 2001, the World Health Organization (WHO) set up the WHO
Research into Global Hazards of Travel (WRIGHT) Project, a large collaborative research study to confirm the
association between VTE and air travel. The results of phase I of the WRIGHT Project were published in June
2007 and are discussed below. Several epidemiologic and pathophysiologic studies were performed during
phase I to determine the magnitude of the risk of VTE due to air travel, the effect of other factors on the
association, and the mechanism by which air travel leads to VTE. Studies into the effect of preventive measures
on VTE risk during travel were deferred to phase II of the project.
RISK FOR TRAVELERS
Several factors have been associated with an increased risk for developing VTE (Box 2-07). Combined effects
have been observed between these established risk factors and different forms of travel. A population-based
case-control study of adults receiving treatment for their first VTE (performed as part of the WRIGHT Project)
found that long-distance travel longer than 4 hours increased the risk of VTE 2-fold compared with not
traveling. The effect was largest in the first week after travel but remained elevated for 2 months
Travel by air increased the risk to the same extent as travel by bus, train, or car, suggesting that the increased
risk of air travel is due primarily to prolonged immobility. Synergistic effects were noted with factor V Leiden
mutations, women who used oral contraceptives, body mass index (BMI) more than 30 kg/m2, and height more
than 1.9 m (approximately 6 ft 3 in). Some of these effects were largest after air travel compared with other
forms of travel. Furthermore, people shorter than 1.6 m (approximately 5 ft, 3 in) had an increased risk of VTE
only after prolonged air travel. These findings suggest that additional factors related to air travel may be
involved in the increased risk for VTE.
Box 2-07. Risk factors for venous thromboembolism (VTE)1
Risk factors for developing VTE include:
Recent major surgery2
Paralytic spinal cord injury
Multiple trauma
Malignancy
Congestive heart failure or respiratory failure
Hormone replacement therapy, oral contraceptive
Previous venous thromboembolism
Inherited hypercoagulable condition
Acquired hypercoagulable condition
Pregnancy
Age >40 years
Obesity
Immobility
Male
1Adapted from Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003 Jun
17;107(23 Suppl 1):I9–16.
2Especially cardiothoracic, abdominal, major orthopedic surgery.
OCCURRENCE
A recent meta-analysis investigating the association between travel and VTE found a 2-fold higher risk for VTE
in travelers compared with nontravelers. Significant variability was noted in the outcomes of the studies
included in the review. This variability was directly related to the method used to select the comparison group
in each study. When studies that used people referred for VTE evaluation as comparisons were excluded from
the meta-analysis, the remaining studies showed a 3-fold higher risk of VTE associated with travel. The risk for
VTE increased with travel duration. Each 2-hour increase in travel duration resulted in an 18% higher risk for
VTE.
Two retrospective cohort studies (performed as part of the WRIGHT Project) address the issue of air travel–
associated VTE incidence. The first was a cohort of 2,499 healthy Dutch commercial pilots. The incidence of
VTE in this group was 0.3 per 1,000 person-years. When the data were adjusted for age and sex, the rate was
not different from that in the general Dutch population. There was no association between the number of hours
flown.
The second study was among 8,755 employees of several international companies and organizations. The
overall incidence of VTE after air travel was 1.4 per 1,000 person-years. The incidence of VTE within 8 weeks
of a long-haul flight (>4 hours) was 3.2 per 1,000 person-years compared with an incidence of 1.0 per 1,000
person-years in employees who did not fly. The absolute risk of VTE per flight more than 4 hours was 1 per
4,656 flights. The rates of VTE were higher in women, especially those using oral contraceptives. Incidence
was also higher in employees with a BMI more than 25 kg/m2 and those with height less than 1.65 m (5 ft 5 in)
or more than 1.85 m (6 ft 1 in). The risk of VTE increased with flight duration and with the number of times the
employee flew during an 8-week period; the risk of VTE tripled in employees who went on 5 or more long-haul
(>4 hours) flights. Each extra flight increased the risk of VTE 1.4-fold. The risk of VTE was highest in the first
2 weeks after a long-haul flight and gradually decreased to baseline after 8 weeks.
Both these studies were performed among populations that were younger (mean age 35–40 years) and healthier
than the general population and are not, therefore, generalizable to a higher-risk population.
CLINICAL PRESENTATION
Symptoms of DVT include swelling, redness, pain, or tenderness and increased warmth over the skin. It may be
difficult to distinguish from muscle strain, injury, or skin infection. Prospective studies have shown that many
leg DVTs are asymptomatic; therefore, the first symptoms may be due to a PE.
Symptoms of PE range from mild and nonspecific to acute, resembling heart attack or stroke. Once a clot has
traveled to the lungs, common symptoms of PE are chest pain and shortness of breath. Other symptoms include
dizziness, fainting, anxiety, and malaise. PE can occur in the absence of overt signs of DVT.
DIAGNOSIS
Specialized imaging tests (duplex venous ultrasound, venography, CT scans, and MRI) are needed to make a
definitive diagnosis of DVT. Helical CT or ventilation-perfusion scans are commonly used to diagnose PE.
PREVENTIVE MEASURES FOR TRAVELERS
Although results are not available for phase II of the WRIGHT Project, several randomized controlled trials
have been performed to assess the effect of prophylactic measures on VTE risk after air travel. All studies
examined the risk of asymptomatic DVT in travelers making flights ≥7 hours. All travelers were encouraged to
do regular exercises and to drink nonalcoholic beverages during the flight. DVT was diagnosed by venous
ultrasound from 90 minutes to 48 hours after the flight. Interventions that were studied include compression
stockings, aspirin, low-molecular weight heparin, and various natural extracts with anticoagulant properties.
Compression stockings (10–20 mm Hg and 20–30 mm Hg) were shown to significantly reduce the risk of
asymptomatic DVT; however, 4 travelers wearing compression stockings in one study developed superficial
thrombophlebitis. Symptomatic DVT and PE were not observed in any of the travelers enrolled in the studies.
The LONFLIT3 study was a randomized trial conducted to compare the effects of aspirin and a low-molecular-
weight heparin (enoxaparin) versus no treatment in the prevention of VTE in 300 high-risk patients (such as
previous DVT, coagulation disorders, severe obesity, limitation of mobility due to bone or joint problems,
neoplastic disease within the previous 2 years, or large varicose veins). Aspirin (400 mg daily for 3 days,
starting 12 hours before air travel) did not reduce the frequency of DVT compared with controls (4.8% in
people not on prophylaxis; 3.6% in people taking aspirin). No DVT and one superficial thrombosis were
identified in people using enoxaparin prophylaxis (1 dose at 1,000 IU per 10 kg of body weight injected 2–4
hours before the flight). Although these results are encouraging for the use of low-molecular-weight heparin to
prevent VTE in high-risk patients, the study size and number of patients with DVT were small. Currently no
convincing data suggest that pharmacologic interventions reduce the risk of significant VTE in low-risk
travelers.
The American College of Chest Physicians (ACCP) published the eighth edition of their Antithrombotic and
Thrombolytic Therapy Evidence-Based Clinical Practice Guidelines in a June 2008 supplement to the journal
CHEST. Recommendations for long-distance travel associated VTE are the following:
For travelers who are taking flights >8 hours, the following general measures are recommended:
avoidance of constrictive clothing around the lower extremities or waist, maintenance of adequate
hydration, and frequent calf muscle contraction (ACCP grade 1C: strong recommendation, low-quality
evidence).
For long-distance travelers with additional risk factors for VTE, the general measures listed above are
recommended. If active thromboprophylaxis is considered because of a perceived high risk of VTE, the
use of properly fitted, below-knee graduated compression stockings, providing 15–30 mm Hg of
pressure at the ankle (ACCP grade 2C: modest recommendation, low-quality evidence) or a single
prophylactic dose of low-molecular-weight heparin, injected before departure (ACCP grade 2C: modest
recommendation, low-quality evidence) are suggested.
For long-distance travelers, the use of aspirin to prevent VTE is not recommended (ACCP grade 1B:
strong recommendation, moderate-quality evidence).
BIBLIOGRAPHY
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