Air travel and risk of venous thromboembolism

Abstract

The possible link between long journeys, particularly by air, and subsequent risk of developing venous thromboembolism (VTE) has recently received great attention in the media. Until recently, there were a few studies investigating such an association, and the evidence was limited to either small, retrospective studies [1,2], case reports [3,4], or animal studies [5]. Case reports have received most attention, particularly because of coverage in the media. The most celebrated patient is probably former US President Richard M. Nixon, who in 1974 suffered from left-sided deep vein thrombosis (DVT) on board Air Force One, the presidential aircraft, en route from the US to Europe, the Middle East, and the Soviet Union. Despite ongoing anticoagulation treatment, he was hospitalized several times because of serious recurrences of pulmonary embolism (PE). Finally, it was found necessary to ligate the left iliac vein, which was presumed to be the source of embolism. The illness itself and surgical complications reportedly contributed to his not having to testify in the Watergate hearings [6]. Two recent case-control studies have reached different conclusions [7,8]. Ferrari et al. [7] investigated 160 patients with VTE, but only 9 of them had traveled by air, while Kraaijenhagen et al. [8] examined 788 patients with suspected VTE, but again only 17 of these had traveled by air. Both studies included all forms of travel, and they are therefore often erroneously referred as air travel studies. The subgroups of air passengers were obviously too small to conclude with certainty whether there is an association between air travel and risk of VTE. Although we do not presently know how long the potential risk for VTE is sustained after an air flight, the studies are further weakened by long follow-up period, i.e. up to 4 weeks after exposure. This reduces the possibility of finding clots related to the flight itself and increases the possibility that clots may have had other causes. In an interesting cohort study from the Charles de Gaulle Airport in France, Lapostolle et al. [9] investigated the association between exposure time, i.e. length of flying and serious PE. The study embraced more than 135 million air passengers who over a 7-year period traveled to or via the Charles de Gaulle Airport. Fifty-six passengers who sought the airport emergency immediately after landing were confirmed to have suffered serious PE, and the rate of serious PE increased with the length of the flight. The incidence was low and varied from 1 per million air passengers for flights lasting 10 h. However, the study only investigated passengers who were taken to the airport emergency immediately after arrival. Passengers who either died on the plane, passengers with less serious thrombosis, or thrombosis that produced late symptoms, and patients with asymptomatic thrombosis were not examined or included. Thus, the figures probably describe the tip of an iceberg, and the real risk of VTE may therefore be much greater. Scurr et al. [10] used duplex ultrasonography within 48 h after a long flight in passengers over 50 years of age without risk factors for DVT and showed that up to 10% of the passengers developed signs of DVT. In another study, DVT was not detected by ultrasonography in healthy passengers with no risk factors, but these passengers were younger (mean age of 46 years). In passengers with risk factors such as previous VTE, thrombophilia, restricted mobility, cancer, or varicose veins, DVT was detected in 2.8% of the cases [11]. The results of these two studies have been questioned since ultrasonography may not be reliable for the detection of asymptomatic DVT [12]. The mechanism(s) of thrombosis related to air travel are still unknown, but may be related to at least three different factors, i.e. hypoxic and hypobaric environment inside airplanes, stasis of the lower extremities, and dehydration. Hypobaric hypoxia occurs in all passengers when the air pressure in the aircraft cabin is reduced. Current aircrafts are not designed to tolerate a large difference between the pressure in the cabin and the ambient pressure for a long period of time. For the cabin to tolerate a higher air pressure difference, the aircraft hull would have to be substantially heavier and a large portion of the engine power would go to maintain the cabin pressure. The consequence would be increased fuel consumption and less space for passengers.