Warfarin Institute of America

DEDICATED TO YOUR HEALTH SINCE 2000

Deep Vein Thrombosis and Air Travel: Who is at Risk?

 Debate continues about whether and to what extent air travel predisposes us to blood clots venous thromboembolism (VTE) and pulmonary embolism (PE) ¹. Thanks to the sustained and high profile media reporting of extreme examples, most of the American public polled for their opinion now believes that air travel frequently causes such events¹. Conclusions from case-control studies vary, with some finding little correlation between travel and risk of VTE and others reporting a 2-4 fold increase in risk¹. Whatever the case, the risk for VTE after long-haul flights remains a controversial issue².

 VTE after air travel was first recorded in 1954, but the magnitude of risk has not yet been resolved³. In the past decade at least 200 cases of traveler’s thrombosis have been reported in the literature². Every year the number of passengers traveling over long distances by air increases⁴. International air travel has increased to around 1.56 billion person trips annually³. Pulmonary embolism (PE) and/or deep vein thrombosis (DVT) occurring during or soon after air travel has been termed the "economy class syndrome" ⁵. The syndrome presents as two very different scenarios⁵. The most dramatic scenario is the occurrence of fatal or nonfatal PE during or immediately after a flight⁵. This is the scenario that has caught the attention of the press⁵. The second scenario is the occurrence of PE or DVT days or weeks after a flight⁵.

 VTE is a multifactorial disease resulting from the interaction between genetic and environmental risk factors⁶. Genetic risk factors include abnormalities causing inherited thrombophilia, such as deficiencies of the naturally occurring anticoagulants antithrombin, protein C, protein S, and mutations in genes encoding coagulation factor V (factor V Leiden) and prothrombin⁶. On the other hand, the environmental risk factors associated with an increased risk of VTE include cancer, recent surgery, pregnancy, use of oral contraceptives, and important for our purposes – prolonged immobilization⁶. It has recently been suggested that air travel should be included among transient risk factors for VTE⁶. The risk factors that lead to venous thrombosis during air travel are therefore are described as both patient and cabin-related⁵. Patient-related factors include older age and the presence of other risk factors for VTE⁵. Most of the reported patients have been older than 50 years and obese⁵. Cabin-related factors that are suspected include hypoxia (deficiency in the amount of oxygen reaching body tissues), low cabin humidity, dehydration, smoking, and most importantly prolonged sitting in cramped quarters⁵.

 Several studies have recently been published looking at the evidence associated with a correlation between air travel and increased risk of VTE. One such study noted that the annual risk of VTE is increased by 12% if one long haul flight is taken yearly³. According to the researchers, the average risk of death from flight-related VTE is small compared with that from motor vehicle crashes and injuries at work³. The individual risk of death from flight-related VTE for people with certain pre-existing medical conditions is, however, likely to be greater than the average risk of 1 per 2 million for passengers arriving from a flight³. Overall, VTE is four times more likely to develop within two weeks of arrival from a long haul flight, the so-called "hazard period" ³. Airlines and health authorities should continue to advise passengers on how to minimize risk³.

 Yet another study looked also looked at the risk of thromboembolism during air travel⁷. The average number of passengers per year who arrived at the study airport on flights originating abroad in the period analyzed was 6,839,222⁷. Sixteen cases of VTE were detected over the 6-year period⁷. All patients with travel-associated VTE had flight durations of greater than 6 hours⁷. The overall incidence of VTE was 0.39 per 1 million passengers⁷. On flights that lasted between 6 and 8 hours, the incidence was 0.25 per 1 million passengers, while on flights longer than 8 hours, the incidence was 1.65 per 1 million passengers⁷. Air travel is a risk factor for VTE, and the incidence of VTE increases with the duration of the air travel⁷. However, the low incidence of VTE among long-distance passengers, similar to that observed in other international airports, does not justify social alarm⁷.

 According to Dalen and colleagues, the people who are at greatest risk of VTE with prolonged sitting are the elderly people and those with other risk factors for VTE⁵. The people who are at the very highest risk are those with a history of VTE and those with thrombophilia (disorder in which there is a tendency to the occurrence of thrombosis)⁵. All of those who are at increased risk should avoid prolonged sitting by getting up and walking frequently during long trips by airplane, car, or train⁵. Recent studies suggest that VTE secondary to long air flights may be preventable⁵. Two randomized studies have demonstrated a marked reduction in VTE in patients who wore below-the-knee elastic stockings during long flights⁵. One small study randomized 200 "high-risk" passengers to receive a single dose of low-molecular-weight heparin (1000 IU per 10 kg of body weight) or placebo 2 to 4 hours before long airline flights⁵. The incidence of DVT was 4.8% in the control group⁵. There were no cases in those randomized to low-molecular-weight heparin⁵. It seems clear that prolonged sitting should be avoided, especially in those who are at risk of VTE: the elderly, those with other known risk factors for VTE, and especially those with a history of VTE or who are known to be thrombophilic⁵. In addition to frequent ambulation during long journeys, those at increased risk of VTE may benefit from the use of elastic stockings⁵.

Similarly, Schwarz and colleagues diagnosed venous thrombotic events in 27 passengers (2.8%) and 12 controls (1.0%)². Of these, 20 passengers (2.1%) and 10 controls (0.8%) presented with isolated calf muscle venous thrombosis, whereas 7 passengers (0.7%) and 2 controls (0.2%) presented with deep venous thrombosis². Symptomatic pulmonary embolism was diagnosed in 1 passenger with deep venous thrombosis². All of these individuals had normal findings at baseline ultrasonography². Passengers with isolated calf muscle venous thrombosis or deep venous thrombosis had at least 1 risk factor for venous thrombosis (>45 years of age or elevated body mass index in 21 of 27 passengers)². The follow-up after 4 weeks revealed no further venous thromboembolic event². Long-haul flights of 8 hours and longer double the risk for isolated calf muscle venous thrombosis². This translates into an increased risk for deep venous thrombosis as well². In our study, flight-associated thrombosis occurred exclusively in passengers with well-established risk factors for venous thrombosis²

 Another recent study showed that in the month preceding thrombosis, air travel was reported by 31 patients (15%) and 16 controls (8%)⁶. Thrombophilia was present in 102 patients (49%) and 26 controls (12%), and oral contraceptives were used by 48 patients and 19 controls⁵. The authors concluded that air travel is a mild risk factor for VTE, doubling the risk of the disease⁶. When thrombophilia or oral contraceptive use is present, the risk increases to 16-fold and 14-fold, respectively, indicating a multiplicative interaction⁶. The researchers also concluded that simple behavioral measures could decrease the risk of VTE⁶. Some of the preventive measures recommended during flights include increased water consumption, limitation of alcohol, avoidance of constricting clothes and leg crossing, and mild leg exercise⁶. It has also been pointed out that more aggressive preventive measure such as elastic stockings or anticoagulant drugs should be implemented in high-risk individuals⁶. These individuals include people with thrombophilia or previous VTE⁶.

 The purpose of another recent study was to assess the prevalence of clinical and laboratory risk factors in patients who develop VTE following travel⁸. The design was a case series of 58 consecutive patients presenting with VTE within 30 days of travel⁸. The main outcome measures were prevalence of clinical and laboratory risk factors for VTE, time to presentation, mode and duration of travel⁸. Forty-eight of 58 patients developed VTE following air travel⁸. Thirty-four patients had traveled for more than 8 hours and most patients were diagnosed with VTE within 1 week of completing their journey⁸. Pulmonary embolism occurred in 24 patients, proximal deep vein thrombosis in 23 patients, calf vein thrombosis in four patients, and superficial thrombophlebitis in seven patients⁸. At least one clinical or laboratory risk factor (other than travel) was found in 49 patients and two or more risk factors were found in 30 patients⁸. The most common risk factors were estrogens, a past history of thrombosis, and factor V Leiden⁸. These retrospective uncontrolled data suggest that at least one clinical or laboratory risk factor is present prior to travel in more than 80% of patients who develop VTE within 30 days of travel⁸.

 Perhaps the strongest evidence that prolonged air travel predisposes to thrombosis comes from the travel history of people who present with PE immediately after landing¹. Two independent analyses suggest that the risk of early embolism increases exponentially with travel times beyond 6 hours and may reach 1:200,000 passengers traveling for more than 12 hours¹. The most likely explanation is venous stasis in the legs from prolonged sitting, and there is evidence that elastic support stockings may prevent deep vein thrombosis in people who travel long-distances¹. Case reports suggest that in most cases, travel-related thrombosis has affected people who were also at risk because of previous thrombosis, recent injury, or other predispositions¹.

 In a prospective, controlled study, Schwarz and colleagues examined 160 passengers before and after return from a long-haul flight and 160 age-matched and sex-matched, non-traveling volunteers using venous compression ultrasound⁹. Deep vein thrombosis was not observed in either group⁹. Isolated calf muscle vein thrombosis (ICMVT) was present in 4/160 (2.5%) flight passengers and in 1/160 (0.6%) controls⁹. ICMVT has been described as the first step to developing a DVT⁹. All subjects with ICMVT were clinically asymptomatic, and ICMVT was located in the soleal muscle veins in all four subjects⁹. Three of the four passengers with ICMVT had other risk factors for thrombosis⁹.

 Scurr and colleagues found 12/116 passengers (10%) developed symptomless DVT in the calf (five men, seven women) ⁴. None of these passengers wore elastic compression stockings, and two were heterozygous for factor V Leiden (FVL)⁴. Four further patients who wore elastic compression stockings, had varicose veins and developed superficial thrombophlebitis⁴. None of the passengers who wore class-I compression stockings developed DVT⁴. We conclude that symptomless DVT might occur in up to 10% of long-haul airline travelers⁴. Wearing of elastic compression stockings during long-haul air travel is associated with a reduction in symptomless DVT⁴.

 The so-called LONFLIT study was planned to evaluate the incidence of DVT occurring as a consequence of long flights¹⁰. In the LONFLIT 1 study, 335 subjects at low risk for DVT and 339 at high risk were studied¹⁰. All flights were in the economy class and the average flight duration was 12.4 hours¹⁰. The mean age of the subjects was 46 years with a range from 20-80 years¹⁰. DVT diagnosis was made by ultrasound scans within 24 hours after the flights¹⁰. In low risk subjects no events were recorded while in high risk individuals, 11 had a DVT (2.8%)¹⁰. In the LONFLIT 2 study, the authors studied 833 subjects with a mean age of 44.8 years¹⁰. 422 subjects were used as controls and 411 used below-the-knee compression stockings¹⁰. Again, the average flight duration was 12.4 hours¹⁰. Scans were made before and after the flights¹⁰. In the control group there were 4.5% of subjects with DVT while only 0.24% of subjects had DVT in the stockings group¹⁰. The difference was significant¹⁰. The incidence of DVT observed when subjects were wearing stockings was nearly 19% lower than in the controls¹⁰. In conclusion, long-haul flights are associated with DVT in 4-5% of high risk subjects, and below-the-knee stockings are beneficial in reducing the incidence of DVT¹⁰.

 Yet another study looked at the risk factors for the development of air travel-associated acute VTE¹¹. Eklof and colleagues performed a retrospective study of 254 patients admitted from 1988 to 1993 under the diagnosis of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) that identified 44 patients who developed symptoms during or after air flight¹¹. There were 24 males and 20 females with a mean age of 63 years¹¹. Flight times were 5-17 hours¹¹. Twenty-eight patients (63.6%) had DVT only, five patients (11.4%) PE only, and 11 patients (25%) had a DVT and PE¹¹. Five patient-related risk factors were identified: history of previous DVT (34%), presence of chronic disease or malignancy (25%), hormone therapy (16%), recent lower limb injury (11%), and recent surgery or femoral catheterization (9%)¹¹. We can speculate about the role of seven cabin-related risk factors: low humidity, hypoxia, diuretic effect of alcohol, insufficient fluid intake, smoking, "coach" position, and immobilization¹¹. In travelers with patient-related risk factors, the cabin-related risk factors are superimposed and may increase the risks for air travel-related acute VTE¹¹. Active prophylaxis is recommended¹¹.

 A statement recently issued by the World Health Organization (WHO) declared that "a link probably exists between air travel and venous thrombosis," but "such a link is likely to be small, and mainly affects passengers with additional risk factors" ².

 Editor's Note:  Since this was written, I had a chance to speak with several cardiologists who were contemplating a flight from the US to Australia for a professional meeting.  They were almost all going to give themselves a dose of subcutaneous low molecular weight heparin before each long flight. 

thrombosis and air travel: record linkage study. BMJ. 2003;327:1072-1076.