Published: September 2001

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Travellers' Thrombosis

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Prescriber Update 22: 8-14
September 2001

Medsafe Editorial Team

There is increasing suspicion amongst the travelling public and the media of an association between the occurrence of venous thromboembolism (VTE) and air travel.  However VTE can occur with other forms of travel and hence the term travellers' thrombosis.  Doctors must be aware of the risk factors for travellers' thrombosis, and if appropriate discuss the need for prophylaxis with at-risk patients who are contemplating long-distance travel.  The effectiveness of aspirin or low molecular weight heparin as prophylaxis in moderate and high-risk groups is theoretical at this stage.  It would be prudent to advise all travellers about lower leg exercises, hydration, and the symptoms of VTE.

The added risk of VTE after long-distance travel is unknown

At least 200 cases of deep vein thrombosis and pulmonary embolism (collectively known as venous thromboembolism, VTE) after travel have been reported in the last decade.¹  The background incidence of deep vein thrombosis (DVT) in the general population is approximately 1-2 per 1000 people per year,^1,2,3 and increases with age.⁴  In addition, up to 20% of the total population may have some degree of increased clotting tendency²; therefore it follows that some members of the public are at risk of coincidentally developing DVT when, or soon after, travelling.  However, several case series¹ and two case-control studies^5,6 do suggest an association between travel and a greater risk of VTE, although there is one prospective case-control study⁷ that did not show an association.  Consequently, there remains the possibility that the association could still be coincidental.

Despite paucity of evidence making it difficult to measure the actual incidence of VTE after air travel, or travel of any type, the added contribution of recent long-distance travel to VTE risk has been estimated as 0 to 0.4 per 1000 people per year.²  Using the mid value of 0.2 means that for every one million people taking one long journey in a year, there may be an extra 200 cases due to the risk from travel,² added to a background incidence of 1500 cases of clinically detectable VTE.  This risk estimate is likely to be higher for people with risk factors, and lower for those without.

Travellers' thrombosis rather than economy class syndrome

Immobility when seated was first recognised as a risk factor for the development of DVT in air raid shelters during World War II.⁸  Homans in 1954 reported five cases of DVT after prolonged sitting and suggested that "prolonged dependency stasis, a state imposed by airplane flights, automobile trips and even attendance at the theatre is able, unpredictably, to bring on thrombosis in the deep veins of the legs".⁹

The Select Committee on Science and Technology, House of Lords in the United Kingdom (UK), believes the term 'economy class syndrome' is seriously misleading and the term 'travellers' thrombosis' is more appropriate.²  Many of the published reports include cases of VTE which have occurred in business or first class, or in travellers using other forms of travel.^{5, 10,11}

It is not clear whether there are factors in the environment peculiar to air travel, such as time zone changes, seasonal shifts, air quality and dehydration, which heighten the risk of travellers' thrombosis over other forms of travel.¹  A study¹² in healthy male volunteers showed that hypobaric hypoxia can activate coagulation.  Clearly the various long-distance travel modalities share some similar environmental factors such as immobility, the sitting position, and possibly alcohol intake and use of sedative medicines.  Until more epidemiological evidence is available, travellers should be made aware of the risks of thrombosis associated with travel involving long periods of immobilisation.

Pre-existing risk factors contribute to DVT development and are independent of travel

A review¹ of data from 223 cases of travellers' thrombosis published in 2000 found that most people became symptomatic of VTE within four days (some during the journey itself), although occasionally cases were diagnosed as long as four weeks later.  At least one risk factor for VTE was present in 75-80% of cases, however most of the studies did not include thrombophilia screens.  In contrast, a case-control study⁵ found that post-travel DVT was more often idiopathic and only 25% of cases were associated with risk factors.

Until more evidence is available on the pathogenesis of travellers' thrombosis and from epidemiological studies, the risk factors for VTE with travel are considered to be the same as those for VTE under other circumstances.  The following list is derived from studies of VTE in surgical patients^2:

• Increasing age above 40 years
• Pregnancy
• Former or current malignant disease
• Blood disorders leading to increased clotting tendency
• Inherited or acquired impairment of blood clotting mechanisms
• Some types of cardiovascular disease or insufficiency
• Personal or family history of DVT
• Recent major surgery or injury, especially to lower limbs or abdomen
• Oestrogen hormone therapy, including oral contraception
• Immobilisation for a day or longer
• Depletion of body fluids causing increased blood viscosity.

In addition, there may be risks from varicose veins, obesity and current tobacco smoking.^1,13  The occurrence of VTE may require a combination of these risk factors to be present.^1,3

The minimum prophylactic recommendation is adequate hydration and mobilisation

Recommendations for prophylaxis of travellers' thrombosis are theoretically-based rather than supported by epidemiological evidence.  However, it is recommended that all travellers carry out frequent lower leg exercises, maintain adequate hydration, minimise alcohol intake and avoid sedative medicines.  Table 1 gives further recommendations.

In light of publicity about travellers' thrombosis, many travellers are taking aspirin before and during travel.  However the efficacy data for this are not yet available.  In addition, the benefit of aspirin in thrombosis prophylaxis needs to be weighed against the risks of its adverse effects such as bleeding.¹⁴

Two recent studies^15,16 have examined the effectiveness of elastic compression stockings in the prevention of symptomless DVT after long-haul air travel.  Scurr et al¹⁵ conducted a randomised controlled trial of travellers aged over 50 years with no history of thromboembolic problems, flying in economy class.  The results showed that twelve of the 100 participants not wearing stockings developed symptomless DVT, of whom four required low molecular heparin; whereas no DVTs were detected in the 100 participants wearing the stockings.  The LONFLIT Study16 included a randomised controlled trial exploring the use of stockings versus no stockings in subjects at increased risk of VTE.  They also found that stockings significantly reduced the incidence of VTE.

More needs to be known about the true incidence of DVT occurrence after all types of travel and the clinical significance of symptomless DVT.  The House of Lords has recommended that the UK Department of Health commission case-control research into travellers' thrombosis and preventative measures that may be taken.²  In New Zealand, there is a large prospective cohort study underway (NZATT, New Zealand Air Travellers' Thrombosis study), following 1000 long-distance travellers for VTE incidence.  This study includes a nested case-control design to address risk factor analysis.

Table 1:  VTE prophylaxis recommendations for travellers^1,2

Risk Categories	Risk factors	Prophylaxis
	None	Give travellers the following advice: frequent lower leg exercises regular mobilisation if practical maintain adequate hydration minimise alcohol intake avoid sedative medicines.
Low Risk	Age over 40; obesity; active inflammation; polycythaemia; recent minor surgery (within last three days)	As above plus consider the use of support tights/non-elasticated long socks.
Moderate Risk	Varicose veins; heart failure (uncontrolled); recent myocardial infarction; hormone therapy (including oral contraception and HRT); pregnancy/postnatal; lower limb paralysis; recent lower limb trauma (within six weeks); family history of VTE	All the above plus consider low dose aspirin (if no contraindication) +/- graduated compression stockings.
High Risk	Previous VTE; known thrombophilia; recent major surgery (within six weeks); previous cerebrovascular accident; malignancy	Discuss with travellers the possibility of avoiding or delaying travel.  Otherwise, as above but consider low weight molecular heparin instead of aspirin.

Consumer information is available

Many airlines are now issuing health information leaflets with tickets, as well as providing health advice and information on their web sites.^17,18,19  Information about DVT is also provided by in-flight video and audio channels, and in the airlines' magazines.

In addition, medical practitioners should include advice and education about the symptoms of VTE as part of pre-travel guidance about disease conditions that might be encountered while travelling (e.g. gastroenteritis, malaria).  Doctors have an important role to play in assessing the need for active prophylaxis and recommending preventative strategies for VTE to patients.  Remind patients with known risk factors to check with their doctor prior to embarking on any form of long-distance travel.  Patients with other medical conditions²⁰ (e.g. chronic lung disease, diabetes, otitis media) that may be adversely affected by travel should undergo pre-flight assessment of health status and suitability to travel.

Competing interests (authors): none declared

References

1. Kesteven PJL. Traveller's Thrombosis. Thorax 2000;55 (Suppl 1):S32-S36.
2. House of Lords Select Committee on Science and Technology. Air Travel and Health, Session 1999-2000 5^th Report, HL Paper 121-I. The Stationery Office, London. http://www.parliament.the-stationery-office.co.uk/pa/ld199900/ldselect/ldsctech/121/12101.htm
3. Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999;353:1167-1173.
4. Hansson PO, Welin L, Tibblin G, et al. Deep vein thrombosis and pulmonary embolism in the general population. Arch Int Med 1997;157:1665-1670.
5. Ferrari E, Chevallier T, Chapelier A, et al. Travel as a risk factor for thromboembolic disease. A case control study. Chest 1999;115:440-444.
6. Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients. Arch Int Med 2000;160:3415-3420.
7. Kraaijenhagen RA, Haverkamp D, Koopman MMW, et al. Travel and risk of venous thrombosis. Lancet 2000;356:1492-1493.
8. Simpson K. Shelter deaths from pulmonary embolism. Lancet 1940;ii:744.
9. Homans J. Thrombosis of the deep leg veins due to prolonged sitting. N Eng J Med 1954;250:148-149.
10. Symington IS, Stack BHR. Pulmonary thromboembolism after travel. Br J Chest 1977;17:138-140.
11. Milne R. Venous thromboembolism and travel: is there an association? J R Coll Physicians Lond 1992;26:47-49.
12. Bendz B, Rostrup M, Sevre K, et al. Association between acute hypobaric hypoxia and activation of coagulation in human beings. Lancet 2000;356:1657-1658.
13. Kesteven PJL, Robinson BJ. Clinical risk factors for venous thrombosis associated with air travel. Aviat Space Environ Med 2001;72(2):125-128.
14. Gallus AS, Baker RI. Economy class syndrome. M J Aust 2001;174:264-265.
15. Scurr JH, Machin SJ, Bailey-King S, et al. Frequency and prevention of symptomless deep-vein thrombosis in long-haul flights: a randomised trial. Lancet 2001;357:1485-1489.
16. Belcaro G, Geroulakos G, Nicolaides AN, et al. Venous thromboembolism from air travel: The LONGFLIT study. Angiology 2001;52(6):369-374.
17. http://www.britishairways.com/health
18. http://www.qantas.com.au/flights/essentials/healthinflight.html
19. http://www.airnz.co.nz/travel/travelguide/traveltips.jsp
20. British Airways Health Services. Your patient and air travel - a guide to physicians. eGuidelines http://www.eguidelines.co.uk/eguidelinesmain/guidelines/summaries/wp_air_travel.htm (Note: registration is required to access this web site. Go to eguidelines.co.uk/registration.htm).