Kuipers, S.
Citation
Kuipers, S. (2009, September 24). Air travel and venous thrombosis : results of the WRIGHT study : Part I: Epidemiology. Retrieved from https://hdl.handle.net/1887/14014
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Chapter 8
Summary
S. Kuipers
In venous thrombosis (VT), a blood clot develops in a vein, usually a deep vein of the leg, causing obstruction of the blood flow. This results in swelling, redness and pain of the affected limb. When part of this blood clot detaches, a potentially fatal condition, called pulmonary embolism (PE), may occur. A frequent
complication of venous thrombosis is the post-thrombotic syndrome, a disabling condition with persistent swelling and pain of the affected extremity.
Individuals at older age and those with certain genetic risk factors, such as the factor V Leiden mutation, the prothrombin 20210A mutation, protein S or C deficiency and Antithrombin III deficiency, are at increased risk for developing venous thrombosis. However, this usually does not occur until environmental risk factors are present as well. Common environmental factors that are known to increase the risk of venous thrombosis are surgery (especially orthopedic surgery), trauma, immobilization, plaster cast, malignant diseases, pregnancy or delivery and use of oral contraceptive- or hormone replacement therapy.
Another environmental risk factor that may increase the risk of venous thrombosis is long distance travel.
Long distance travel may lead to blood clot formation due to several
pathophysiological mechanisms. Around 1850, the pathologist Virchow already posed three possible causes of thrombosis: venous stasis, damage of the vessel wall and changes in blood composition. Damage of the vessel wall seems to be more important in the development of arterial thrombosis (such as a myocardial infarction or ischemic stroke). In air travel, both venous stasis and changes in the blood composition may occur. Firstly, venous stasis may be the result of the prolonged immobility that occurs when passengers sit in a cramped position in an airplane seat. Dehydration due to the low air humidity in an airplane may lead to venous stasis as well. Furthermore, changes in the blood composition may arise due to the hypobaric hypoxia present in airplane cabins, exposure to jet fuel or other flight-related factors.
This thesis describes the results of several studies on epidemiological aspects of the association between long distance travel and venous thrombosis.
The first chapter serves as an introduction and provides an outline of the studies in this thesis.
Summary 106
Chapter 2 is a review that summarizes all literature available on the association between travel and venous thrombosis up to January 1st 2007. Both
epidemiological research and studies on possible mechanisms responsible for venous thrombosis during and after travel are discussed. From this review article, we conclude that long distance travel increases the risk of venous thrombosis approximately 2-4 fold. Furthermore, a dose-response relationship between the risk of severe pulmonary embolism and duration of travel strongly suggests a causal association. The mechanism responsible for this increased risk of VT after air travel was not sufficiently studied to draw solid conclusions, but one controlled study showed evidence that not only immobilization but other air travel specific factors lead to coagulation activation.
In the 3rd chapter the use of prophylactic measures to prevent travel-related thrombosis by visitors of three international conferences in Australia was assessed through a survey that was sent to all overseas attendants of these conferences. We showed that a considerable number (over 80%) of them used some kind of preventive measure during travel. The type of preventive measures varied between conference, professional background, risk groups and nationality.
Delegates of a haemostasis and thrombosis conference and especially medical doctors used more aggressive prophylaxis than delegates of the conferences that did not concern thrombosis.
The 4th chapter describes a study in a cohort of frequently flying employees of large international companies or organizations. In this cohort, the absolute risk of developing symptomatic venous thrombosis within 8 weeks of flights longer than 4 hours was 1 in 4656 flights. This risk increased with flight duration, up to 1 in 1264 after flights longer than 16 hours. Furthermore, the risk increased when employees were exposed to several flights in a short period of time (since exposure to air travel was defined as a period of 8 weeks after a flight, these 8- week time-windows were frequently overlapping) and it decreased with time after a long haul flight. The risk returned to baseline after approximately 8 weeks after the flight. Individuals that were most at risk for developing travel-related venous thrombosis in this cohort were young travellers, women – especially those taking oral contraceptives – , individuals who were particularly short or tall and those with a body mass index over 25kg/m2.
In the 5th chapter, the effect of increased coagulation factors and that of
interaction with other risk factors for venous thrombosis in long distance travellers is assessed. In a case-control study amongst 334 long distance travellers, we
number of coagulation abnormalities (factor II, VIII and IX, prothrombin mutation and factor V Leiden mutation) and with the overall number of risk factors present per individual (coagulation factors, high body mass index and oral contraceptive use). The relative risk was highest in female travellers using oral contraceptives who also had high levels of FVIII (odds ratio 51.7, CI95 5.4-498). Combinations with the factor V Leiden mutation were associated with a particularly high relative risk as well. All these effects were superimposed on the relative risk of travel itself, which is about two in this population.
In the 6th chapter, the effect of other transient risk factors for venous
thrombosis on the risk of air-travel related venous thrombosis was evaluated.
Transient risk factors that had the most pronounced effect on the risk of travel-related venous thrombosis were recent surgery, oral contraceptive use and malignant diseases.
The 7th chapter describes the results of a study on occurrence of venous thrombosis amongst commercial airline pilots in the Netherlands. In this follow up study amongst 2630 pilots, the incidence rate of venous thrombosis was 0.3/1000 person years (CI95 0.1-0.6). This incidence rate was lower than in the general Dutch population and in a population of frequently flying employees of international companies or organisations. Compared to the general Dutch population, the age- and sex adjusted relative risk for venous thrombosis was 0.8 (CI95 0.7-1.0). The incidence rate of venous thrombosis in the airline pilots did not increase with number of flight-hours per year, nor was it associated with rank of the pilots.
From all studies described in this thesis, we conclude that the absolute risk of venous thrombosis after long distance travel in the general population is not high enough to promote widespread use of aggressive prophylaxis, such as anticoagulant therapy. The general advice that is now provided to air travellers (prevention of venous stasis by walking around, refraining from sleeping medication and drinking plenty non-alcoholic beverages) seems sufficient for most healthy air travellers although the effect of these measures has insufficiently been established. However, some subgroups of travellers are at increased risk for developing travel-related venous thrombosis, especially when several risk factors are combined in one traveller. For these subgroups of people with a highly increased risk, the risk-benefit ratio may favour the use
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of prophylactic measures. To date, it is not known which prophylactic measure is most suitable for prevention of travel-related thrombosis. Large randomized trials are required to assess who would benefit most from special exercises, elastic compression stockings, mechanical devices that promote venous blood flow or low molecular weight heparin.
