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Abstract & Commentary
Synopsis: There is an association between long-distance air flights and venous thromboembolism, but the role of traditional risk factors and prophylactic measures requires more study.
Source: Hughes RJ, et al. Lancet. 2003;362:2039-2044.
Virchow hypothesized that blood stasis is an important factor in venous thrombosis, and it undoubtedly is a major factor in the observed association between air travel and venous thromboembolism. However, the importance of other risk factors and the precise frequency of air travel-related thromboembolism are uncertain. Thus, Hughes and colleagues in New Zealand took advantage of their geographic isolation to study this problem by enrolling volunteers traveling at least 4 hours by air who were going to return within 6 weeks. Excluded were those with previous venous thromboembolism, on anticoagulants, post-major surgery within 6 weeks, with cancer within 6 months, with renal insufficiency, or pregnant. Enrollment stopped at 1000 subjects. All had baseline D-dimer studies, and 83 were excluded because of elevated values. Another 39 failed to return for their follow-up visit, leaving a total study population of 878. All subjects were evaluated clinically and told to keep a diary about their pre-, post-, and in-flight activities. Upon return they were contacted within 72 hours for blood work including D-dimer, thrombophilic risk factors, and anticardiolipin antibodies. D-dimers were repeated at 2 weeks and 3 months after travel, and any positive values or symptoms suggestive of venous thrombosis were evaluated further by lower extremity ultrasonography, pulmonary CT angiography, or ventilation perfusion scintigraphy.
The frequency of confirmed venous thromboembolism (VTE) was 1% (9/878)—4 with pulmonary emboli, 3 with proximal, and 2 with distal lower limb deep venous thrombosis. The mean total duration of air travel was 39 hours, most of which was in economy class (about 80%). With total air travel of £ 24 hours, 10% of subjects used compression stockings and when total air travel exceeded 24 hours, 18% did. Of the 112 subjects who were evaluated for venous thromboembolism, 76 were studied on initial return contact, 30 at 2 weeks, and 8 at 30 days. All of the subjects with confirmed VTE had a positive D-dimer at the initial review; 6 had risk factors for VTE pre-travel; 2 had thrombophilic abnormalities discovered in the post-travel testing; 2 traveled exclusively in business class; 5 used aspirin; and 4 wore compressive stockings. When those with VTE were compared to those without, there was no difference in length of travel (42 vs 39 hours), but no one with a total travel duration < 24 hours had VTE. Hughes et al concluded that there is an association between long-distance air flights and VTE, but the role of traditional risk factors and prophylactic measures requires more study.
Comment by Michael H. Crawford, MD
The major finding of this study is that long-duration air travel is associated with VTE even in patients with low to moderate risk, since high-risk patients were excluded. VTE was associated with total flight durations > 24 hours. Since the longest flight known from New Zealand is 14 hours, risk was associated with multiple flights within the 6-week window of the study. Since patients were studied when they returned, Hughes et al do not know which flight was the culprit. Two subjects were evaluated after outward flights because of symptoms suggesting VTE, but neither had VTE confirmed.
Thus, their data suggest that most VTE events occur after multiple flights within 6 weeks, usually after return from the trip.
The value of prophylactic measures was difficult to determine. One in 6 subjects used compressive stockings and almost one-third were on aspirin, which suggests that the study group may have been better informed than the more general flying public about the risks of VTE. Thus, the incidence of 1% in this study may have been an underestimate of the risk of VTE with total air travel > 24 hours. Also, the value of in-flight exercise, hydration, avoidance of alcohol, and other popular prophylactic measures could not be determined. However, some patients with documented VTE did use compressive stockings and aspirin and flew business class, so it is unlikely that these 3 measures are completely preventative. The only sure-fire preventative strategy was to not take air trips lasting > 24 hours total.
Dr. Crawford is Professor of Medicine, Associate Chief of Cardiology for Clinical Programs; University of California, San Francisco, Calif.