Behind The Medical Headlines

Flight-related DVT

• Dr D Dawson, Emergency Department, Manchester Royal Infirmary, Manchester, England
• Dr K Mackway-Jones, Emergency Department, Manchester Royal Infirmary, Manchester, England

Summary

As long-haul travel becomes more popular and affordable, public concern has increased about the possible connection between long-haul travel and the development of potentially-fatal deep vein thromboses (DVTs). In this article Dr Debbie Dawson and Dr Kevin Mackway-Jones examine the evidence in relation to flight-related DVT.

Declaration of interests: No conflict of interests declared

Earlier this year, a BBC news item¹ brought to our attention, once again, the issue of DVT and its association with travel, in particular long-haul air travel. It has yet to be fully established that air travel is a risk factor for DVT, though an association between the two is generally accepted and conceivable despite the limited evidence available to us. Most research in this field has been carried out using case controlled studies where selection bias reduces reliability of results. Randomised controlled trials (RCTs) are not a useful means of assessing the incidence of DVT from air travel due to the impracticalities of randomising, the large number of passengers that would be required to provide accurately powered results,² and also because occurrences of flight-related DVT are low and often asymptomatic. In spite of the limited evidence available, a systematic review³ investigating DVT in relation to air travel found the incidence of symptomatic DVT ranged from 0% to 0.28%; and the incidence of asymptomatic DVT ranged from 0% to 10.34%.

The condition and its potential to evolve into pulmonary embolism (PE), has led to a great deal of media attention, with phrases such as ‘economy class syndrome’ and ‘travellers’ thrombosis’ being coined. Consequently, it is a cause for widespread concern. In addition, researchers are still trying to ascertain why flight-acquired DVT occurs. While prolonged immobilisation has been assumed to be the reason for the condition, research indicates that it may not be the only mechanism involved. What is also unclear is exactly who is at risk and what (if any) advice and preventative measures should be recommended by clinicians.

Air travel vs immobility

It is inevitable during the course of a long-haul flight for passengers to experience periods of prolonged immobilisation. Immobility is certainly a recognised risk factor associated with DVT as lack of muscle motion leads to blood stasis which in turn can lead to thrombus formation. Other situations where mobility is decreased, such as surgery, hospitalisation or limb paralysis, are also acknowledged for their potential to precipitate a diagnosis of DVT. As a result, it is generally accepted that immobilisation during long-haul air travel is the foundation of flight-related DVT.

It is unclear whether the same risk applies to other modes of prolonged travel or sitting, for example, long-distance coach journeys. This question complicates the whole flight-related DVT issue and has led to theories that there are additional underlying risk factors specific to air travel that increase the risk of DVT.

A recent study in the Lancet⁴ attempts to provide further insight into this particular uncertainty. The aim of the study was to discover whether flying leads to a hypercoagulable state. The researchers measured activated coagulation markers, thrombin-antithrombin complex (TAT), prothrombin fragment 1 and 2 (F1 and F2) and D-dimer, in a sample of 71 healthy volunteers aged between 18 and 40 years; some of this number included had the factor V Leiden mutation and/or took the oral contraceptive pill, both of which are recognised risk factors for venous thrombosis. Blood samples were taken before, during and after an eight-hour flight; the volunteers then had the same tests performed for two additional control scenarios, eight hours of movie-watching and daily life, with a 2–3 week gap between each session.

This research demonstrated more coagulation abnormalities after a flight than after movie-watching or normal daily activity. Those found to have the highest rise in activated coagulation markers had both the factor V Leiden mutation and took the oral contraceptive pill. No participants developed an actual venous thrombosis during the course of the study. The researchers conclude their results demonstrate that flight induces a mechanism for thrombus formation in addition to immobilisation alone, in some individuals.

One possible mechanism for thrombus formation associated with flight is a condition known as ‘hypobaric hypoxia’. This condition can occur due to decreased pressure in the aircraft cabin resulting in a diminished supply of airborne oxygen and might induce coagulation.⁵ However, a recent study failed to substantiate this possibility.⁶

Who is at risk?

Formation of a DVT often involves the cumulative effects of multiple risks. It is therefore advisable for those who already have high or moderate risk factors associated with the condition to avoid additional risk factors. Thus, for example, an individual with a previous DVT, who is obese and over 50 years of age, who requests hormone replacement therapy, may be advised against taking it. Where additional risk factors cannot be avoided, prophylactic measures during times of increased risk, as with hospitalisation, surgery and pregnancy should be considered in an attempt to avoid acute thrombus formation. Low molecular weight heparins might be considered for these individuals.

Those with predisposing risk factors for DVT ought to regard long-haul flight as an additional risk factor, and should consider a preventative intervention to avoid flight- related thrombosis; available evidence suggests that though these events are rare, they are more likely to occur in those at increased high risk. Not all predisposing risk factors threaten the same degree of risk and a physician should be consulted regarding an individual’s relative risk prior to a long-haul air journey.

How to prevent DVT

Primary care physicians are often challenged by worried expectant travellers regarding measures to help avoid flight-related DVT. They may be hesitant to prescribe pharmacological interventions because of the potential side effects, yet be sceptical regarding the benefits of mechanical aids, namely elastic compression stockings.

Both LMWH⁷ and elastic compression stockings⁸ have been shown to reduce the risk of travel-related DVT and its symptoms. Cesarone et al.⁷ compared LMWH, high-dose aspirin and no prophylaxis by randomising 300 high-risk participants (249 completed the study). The results showed thrombotic events (including ‘superficial events’ – thromboses in the superficial veins of the leg which should not be classified as DVTs) occurred in 4.8% of the no prophylaxis group, 3.6% of the aspirin group, and in 0.6% of the LMWH group.

Elastic compression stockings are known to be effective in preventing DVT in hospitalised patients,⁹ and in individuals with a previous DVT, they reduce the risk of thrombus recurrence and damage caused by post-thrombotic syndrome (PTS).¹⁰ The value of these stockings in relation to protection for long-haul flight passengers has been evaluated in a systematic review, including the results of ten trials that randomised between compression stockings and no stockings.⁸ A pooled sample of 2,856 participants, with varying degrees of risk, whose flights were of at least seven hours were included. There were no deaths, PEs or DVTs reported during the research; during follow-up, 50 participants developed asymptomatic DVT, five from those randomised to wear stockings and 45 from those without stockings (P<0.00001). The researchers also noted that wearing stockings had a significant impact on reducing oedema in the legs. In those at low or moderate risk, 1.45% (21 out of 1,446) developed asymptomatic DVT compared with 2.43% (29 out of 1,191) of those at high-risk. Differentiating between low- and moderate-risk individuals would have been of interest here, but in practical terms, 90% of all events occurred in those without stockings, regardless of risk.

Post-flight trouble: what to do

There have been several media reports of travellers going on to develop overt DVTs and/or PEs. The clinical diagnosis of PE is notoriously difficult, and investigation is always required where individuals present with suggestive symptoms. Travellers who develop leg stiffness, pain or swelling, or chest tightness, pain or breathlessness, in the weeks after long-haul air travel should consult a doctor, and doctors consulted by such travellers need to consider DVT and PE very seriously.

References

1. http://news.bbc.co.uk/1/hi/health/4788774.stm
2. Adi Y, Bayliss S, Rouse A, Lip G, Taylor RS. Air travel as a risk factor for venous thromboembolism (VTE) and the effectiveness of preventative measures. West Midland Health Technology Assessment Group. Department of Public Health and Epidemiology, University of Birmingham; Report No. 39; 2002.
3. Adi Y, Bayliss S, Rouse A, Taylor RS. The association between air travel and deep vein thrombosis: systematic review and meta-analysis. BMC Cardiovascular Disorders 2004; 4(7):1–8.
4. Schreijer AJ, Cannegieter SC, Meijers JC, Middeldorp S, Buller HR, Rosendaal FR. Activation of coagulation system during air travel: a crossover study. Lancet 2006; 367(9513):832–8.
5. Crosby A, Talbot NP, Harrison P, Keeling D, Robbins PA. Relation between acute hypoxia and activation of coagulation in human beings. Lancet 2003; 361:2207–08.
6. Toff WD, Jones CI, Ford I et al. Effect of hyperbaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function and endothelial activation. JAMA 2006; 295:2251–61.
7. Cesarone MR, Belcaro G, Nicolaides AN et al. Venous thrombosis from air travel: the LONFLIT3 study – prevention with aspirin vs low-molecular-weight heparin (LMWH) in high-risk subjects: a randomized trial. Angiology 2002; 53(1):1–6.
8. Clarke M, Hopwell S, Juszczak E, Eisinga A, Kjeldstrom M. Compression stockings for preventing deep vein thrombosis in airline passengers. The Cochrane Database of Systematic Reviews 2006; 02:CD004002.
9. Amaragiri SV, Lees TA. Elastic compression stockings for prevention of deep vein thrombosis. The Cochrane Database of Systematic Reviews 2000; 03:CD001484.
10. Prandoni P, Lensing AW, Cogo A et al. The long-term clinical course of acute deep venous thrombosis. Annals of Internal Medicine 1996; 125(1):1–7.