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Air travellers are rightly concerned to know the level of risk, who is likely to be affected, and what precautions they should take. Answers are, however, constrained by a serious lack of definitive information, as the evidence is limited to case series of DVT or PE discovered during or soon after air travel, and a few case-control studies with limited power and contradictory results.

Prolonged travel in a seated position can cause venous stasis, so that an association of VTE with travel would be consistent with Virchow's classic postulate that venous stasis contributes to VTE. However, the present evidence regarding air travel as a cause of VTE is circumstantial and could be misleading. VTE is a common disorder with an annual incidence of about one per 1000 population for DVT and 0.5 per 1000 for PE.¹⁰ Its incidence is age-dependent and rises to nearly 1% per annum in the elderly.¹¹ Given the high community prevalence of VTE and exponential growth in worldwide air travel by all age groups, the reports of flight-related VTE from isolated islands and at busy airports could therefore be mere coincidence. Clinical suspicion of VTE is notoriously misleading, so that retrospective reports might be contaminated by diagnostic bias, and recall bias could influence surveys of predisposing air travel.

Prospective case-control studies seek to minimise bias and estimate risk by obtaining a history of travel from patients with VTE and also from contemporary age-matched and sex-matched controls. Two recent studies from cities with busy international airports have given opposing results. In Nice, 39 of 160 patients with VTE (24.4%) had travelled during the previous four weeks (nine by plane, 28 by motorcar and two by train), compared with 7.5% of 160 age-matched but not sex-matched controls visiting a cardiology outpatient clinic. In this study, recent travel raised the odds ratio (OR) for VTE to 4.0 (95% confidence interval, 1.9-8.4; P < 0.0001).¹² By contrast, when 788 patients with a clinically suspected DVT were interviewed in Amsterdam before diagnostic testing, recent travel was no more prevalent in the 186 patients who had DVT than in the 602 where tests excluded DVT (the OR for DVT after any recent travel, prolonged travel, or air travel was 1.0; 95% CI, 0.3-1.4).¹³ These case-control studies do not decide the issue, as the control groups were suboptimal^12,13 or the study was too small to exclude an important effect of prolonged air travel.¹³

In the absence of good evidence to the contrary, it is prudent to assume that air travel can provoke VTE, although the absolute risk remains uncertain and is probably quite small in most people. This conclusion derives from the Paris airports emergency medical service report.³ By relating the number of people with PE detected during or immediately after a flight to the total number of arrivals, the report derived an overall incidence of about one PE per 3 000 000 arriving travellers³ ("true" risk is likely to be somewhat higher, as about two-thirds of travel-related VTE presents after patients leave the airport¹⁴). The Paris airports report also observed an obviously greater incidence when travel times were longer than 12 hours.³ As 10 of the 11 inflight deaths from PE recorded in the Heathrow report occurred during prolonged flights,⁴ it is likely that travel duration will prove to be important. It is essential that this still-isolated information is verified and extended with further studies.

Advice on prevention is based on assumptions about pathogenesis. In addition to the presumption of venous stasis, there are studies of aircrew or volunteers during prolonged real or simulated flights that suggest dehydration,^15,16 stress and climatic change,¹⁵ and early activation of the blood-clotting system¹⁷ might also contribute. Business and first class passengers are not immune, so more generous seating space is unlikely to be the answer (and "economy class syndrome" is most likely a misnomer).

The following general advice has no direct supporting evidence but is common sense, harmless, inexpensive, and likely to be appropriate, particularly for flights longer than 6-8 hours.^18,19 These general precautions are directed at preventing venous stasis and include regular foot exercises to activate the plantar and calf muscle pumps, a generous fluid intake, avoiding excessive alcohol (especially when combined with the use of hypnotics), and wearing loose clothing while travelling. Prolonged movement about the cabin during flight is discouraged because this may bring other hazards, including from unexpected clear air turbulence.

Travellers with an above-average risk of thrombosis should seek specific medical advice on additional preventive measures before travelling. Case series suggest that people with previous VTE, chronic venous insufficiency, recent surgery, chronic heart and lung disease, cancer, old age and those who are overweight are all at greater than average risk. Oral contraceptives, hormone replacement and inherited thrombophilia (including factor V Leiden) may predispose, but there is no good published evidence for this. Screening for factor V Leiden (activated protein C resistance) is not recommended in this or any other context if there is no personal or family history of VTE, as about 5% of people of European descent have this polymorphism, and most will never develop thrombosis.¹¹

As a generalisation, it usually takes two or three risk factors acting together to provoke VTE,¹¹ and, as this is likely to apply also in travellers, it is people with several concurrent risk factors who are most likely to require specific prophylaxis.

Aspirin alone is not likely to be appropriate, as the evidence that aspirin prevents DVT or PE is highly controversial and the plausible level of risk reduction is small.^20,21 Prescribing aspirin for all travellers may also cause sufficient excess bleeding to negate any benefit. Graded pressure support stockings to be worn during flight must be carefully fitted: too tight and they become a tourniquet, too loose and they are ineffective. And they are contraindicated in some people with advanced peripheral vascular disease. People at highest risk (including those with previous VTE) should consider self-injecting a low molecular weight heparin before and perhaps for some days after travel.

Few people die of PE without some warning from unexpected breathlessness, chest pain, or leg symptoms. Information kits about DVT and PE, predisposing factors and various clinical presentations should therefore be widely distributed to travellers before they leave home. People should know that, although symptoms of VTE may arise during flight, they are more often first noticed some time after landing. More importantly, we need better evidence. If the present media crisis and federal inquiry brings a greater awareness that VTE may develop during or soon after prolonged travel, and if it triggers a productive collaboration of airlines with investigators to measure the real risk and evaluate preventive measures, then it will have served a useful purpose.

Alex S Gallus
Professor of Haematology and Director of Pathology Services
Flinders Medical Centre and Repatriation General Hospital
Adelaide, SA

Ross I Baker
Director, Thrombosis and Haemophilia Service, Royal Perth Hospital and
Clinical Senior Lecturer in Medicine, University of Western Australia
Perth, WA

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©MJA 2001
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