Deborah Nicolls Barbeau

Background

Venous thromboembolism (VTE) consists of two related conditions: 1) deep vein thrombosis (DVT) and 2) pulmonary embolism (PE). DVT occurs when there is a partial or complete blockage of a deep vein 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 two- to four-fold increased risk of VTE following air travel. In 2001, the World Health Organization 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 goals of this project are to determine the magnitude of the risk of VTE due to air travel, to determine the effect of other factors on the association, and to study the effect of preventive measures on risk. The results of Phase I of the project were published recently. Phase II will address the effect of preventive measures.

Risk for Travelers

Several factors have been associated with an increased risk for developing VTE (Box 2-4).

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 found that long-distance travel (≥4 hours) doubled the risk of VTE. The effect was greatest 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, BMI >30 kg/m², and height >1.9 m (approximately 6 ft 3 in). Some of these effects were greatest following air 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.

Occurence

Two recent retrospective cohort studies 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 organizations. The overall incidence of VTE following flights >4 hours was 1.4 per 1,000 person-years. The absolute risk of VTE 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 >25 kg/m² and those with height <1.65 m (5 ft 5 in) or >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 five 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 are 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.

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 (e.g., duplex venous ultrasound, venography, computed tomography (CT) scans, and magnetic resonance imaging) 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

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. No significant effect was seen in any of the pharmacologic interventions. Compression stockings (10–20 mm Hg and 20–30 mm Hg) were shown to significantly reduce the risk of asymptomatic DVT; however, four 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.

All travelers should keep hydrated, wear loose-fitting clothing, and make efforts to walk and stretch at regular intervals during long-distance travel. Compression stockings may be beneficial to travelers with other risk factors for VTE. Currently no convincing data suggest that pharmacologic interventions reduce the risk of significant VTE during travel.

The American College of Chest Physicians published the 8th edition of their Antithrombotic and Thrombolytic Therapy Evidence-Based Clinical Practice Guidelines in a June 2008 Supplement to 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 (Grade 1C).
• For long-distance travelers with additional risk factors for VTE, we recommend the general measures listed above. If active thromboprophylaxis is considered because of a perceived high risk of VTE, we suggest the use of properly fitted, below-knee graduated compression stockings (GCS), providing 15–30 mm Hg of pressure at the ankle (Grade 2C), or a single prophylactic dose of low-molecular-weight heparin (LMWH), injected prior to departure (Grade 2C).
• For long-distance travelers, we recommend against the use of aspirin for VTE prevention (Grade 1B).

References

1. Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I9–16.
2. World Health Organization. WHO Research into Global Hazards of Travel (WRIGHT) project: Final Report of Phase I. Geneva (Switzerland): World Health Organization; 2007 [cited 2008 May 30]. Available from:http://www.who.int/cardiovascular_diseases/wright_project/en.
3. Kuipers S, Cannegieter SC, Middeldorp S, et al. The absolute risk of venous thrombosis after air travel: a cohort study of 8,755 employees of international organisations. PLoS Med. 2007;4(9):e290.
4. Goodacre S, Sutton AJ, Sampson FC. Meta-analysis: the value of clinical assessment in the diagnosis of deep venous thrombosis. Ann Intern Med. 2005;143(2):129–39.
5. Kuipers S, Schreijer AJ, Cannegieter SC, et al. Travel and venous thrombosis: a systematic review. J Intern Med. 2007;262(6):615–34.
6. Geerts WH, Bergqvist D, Pineo GF, et al.; American College of Chest Physicians. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):381S–453S.