Amsterdam, the Netherlands - Hours spent in cramped seating on airplanes is not the only cause of venous thrombosis (VT), a new crossover study suggests[1]. Researchers who compared markers of anticoagulation and fibrinolysis in people who spent eight hours on a plane with those of people who spent eight sedentary hours watching movies at sea level or just going about their daily lives say factors like low oxygen levels and reduced atmospheric pressure may help explain the increased thrombin generation on airplanes.

Commenting on the study to heartwire, senior author Dr Frits R Rosendaal (Leiden University Hospital, the Netherlands) said he and his coauthors were surprised to see that being sedentary at sea level was so different from sitting for long periods in a plane. Previous studies have concluded that the main contributor to so-called "economy-class syndrome" was too many hours spent sitting during long-haul flights.

"While this does not take away from immobilization as a major cause of thrombosis, it does show that something else contributes to risk while sitting in an airplane," he said. "We cannot know for sure what this would be and cannot rule out factors such as stress or air pollution, but the hypobaric hypoxia in an airplane seems a likely candidate."

Air pressure in an airplane is not maintained at what it is at sea level, he noted, but rather is equivalent to atmospheric pressure on a 7000- to 8000-ft mountain.

Individuals who were carriers of the factor V Leiden genetic mutation or who were taking oral contraceptives were at higher risk from air travel than individuals without these risk factors, Dr Anja JM Schreijer (Academic Medical Center, Amsterdam, the Netherlands) et al write in the March 11, 2006 issue of the Lancet.

Schreijer et al measured anticoagulation and fibrinolysis activation markers in 71 healthy volunteers prior to, during, and after an eight-hour flight, then again before, during, and after an eight-hour "movie marathon," and finally over eight hours of daily living. Individuals known to have the factor V Leiden mutation as well as women taking oral contraception were intentionally included in the study.

The authors report that median concentrations of thrombin-antithrombin (TAT) complex increased during the flight but actually decreased following the time in the cinema and after eight hours of daily life. A high response in TAT levels occurred in 17% of individuals after flying, but much lower responses were seen in the other two settings. Higher responses also occurred in a combination of TAT, markers of activated coagulation (prothrombin fragment 1 and 2), and D-dimer concentrations after the flight than after the other two settings. The changes were most marked in "susceptible" participants, namely those taking oral contraceptives or carrying the factor V Leiden mutation.

"We conclude that the coagulation and fibrinolytic system are activated in some susceptible individuals after an eight-hour flight, indicating an additional mechanism to immobilization for air-travel-related thrombosis," the authors write. Most likely contenders are the reduced atmospheric pressure and lower oxygen levels found on airplanes, they suggest. Other factors, such as dehydration and anxiety, while possible contributors, were unlikely to have affected participants in their study, Schreijer et al add.

To heartwire, Rosendaal emphasized that even though air travel confers an approximately threefold increase in thrombotic risk, "this is not an enormous risk in the absolute sense." Overall, it is something like 1:5000 travelers for flights over four hours, he adds, although there are "risk groups, risk flights, and risk behaviors that increase the risk."

In an accompanying Comment, Dr Hans Stricker (Ospedale La Carita, Locarno, Switzerland) notes that strategies such as intermittent calf contraction to improve blood return, avoidance of alcohol or sedatives, and use of compressive stockings may help reduce the risk of potentially fatal thromboembolism during and after flights [2]. While 400-mg aspirin for three days may not be effective, single-dose, weight-adjusted low-molecular-weight (LMW) heparin may be effective in certain higher-risk individuals.

"We do not favor an indiscriminate use of prophylactic heparin because the incidence of mostly asymptomatic and distal deep vein thrombosis is estimated to be less than 4% after long-haul flights and fatal pulmonary embolism is rare," Stricker writes.

That said, he adds, "The study by Schreijer and colleagues shows us that women on oral contraception and individuals with a mutation of factor V should be offered the possibility of extended prophylactic measures, such as LMW heparin or compressive stockings."

For his part, Rosendaal told heartwire that his primary recommendation for people concerned about their risk of VT during air travel is regular exercise.

"Elastic stockings, aspirin, and stronger antithrombotic drugs are not without risk—ill-fitted elastic stockings may well cause thrombosis, and antithrombotic drugs can induce hemorrhage. I think none of these interventions have a proven positive benefit/risk ratio, and indiscriminate use should be discouraged. Since it is difficult to imagine a side effect of exercise, I recommend regular exercise during prolonged travel."

He does not advocate screening for factor V Leiden because his recommendations would be no different for people with this mutation than for people without it. Screening would only be "costly" and "cause misery" without altering preventive strategies, he said.