Customize your JAMA Network experience by selecting one or more topics from the list below.
PULMONARY EMBOLISM (PE) and/or deep vein thrombosis (DVT) occurring during or soon after air travel has been termed the economy class syndrome.1 Three reports in this issue of the ARCHIVES provide additional insights regarding this syndrome.2-4
The syndrome presents as 2 very different scenarios. The most dramatic scenario is the occurrence of fatal or nonfatal PE during or immediately after a flight. This is the scenario that has caught the attention of the press (and some personal injury lawyers). The second scenario is the occurrence of PE or DVT days or weeks after a flight.
Lapostolle et al5 described 56 patients who were diagnosed with PE after arrival at Charles de Gaulle airport (Paris, France) from 1993 to 2000. In each case, the symptoms occurred during the flight, on standing on arrival, or in the Jetway. All had traveled more than 2480 miles (3968 km). Fortunately, only 1 patient died, and the incidence of PE was low: 56 cases of PE among 135 million passengers arriving at the airport during a 7-year period (0.4 cases of PE per 1 million arriving passengers). They found that the incidence of PE increased as a function of the distance traveled. The incidence for those traveling less than 3100 miles (4960 km) was 0.01 case per 1 million passengers compared with 1.5 cases per 1 million passengers for those traveling more than 3100 miles (4960 km) and 4.8 cases per 1 million passengers for those traveling more than 6200 miles (9920 km). Pérez-Rodriguez et al2 report a similar study from Madrid, Spain, in this issue of the ARCHIVES. During a 6-year period, 16 patients were diagnosed with PE on arrival from international flights to Madrid. The incidence of PE was identical to that reported from Paris by Lapostolle et al5: 0.39 cases of PE per 1 million arriving passengers. Pérez-Rodriguez et al2 also noted an increased incidence in longer flights.
Did these pulmonary emboli originate from DVT that formed during the flight, or did they originate from DVT that was present before the flight began? Cheung and Duflou6 reported the results of postmortem examination of 14 patients who died of PE during flight or shortly after arriving at the Sydney airport (Sydney, Australia) during a 6-year period. In 4 cases, the pulmonary emboli were old, indicating that the PE had occurred prior to the flight. In 9 cases, the pulmonary emboli were "fresh," consistent with their having reached the lungs during the flight. However, the duration that they had been in leg veins was not certain. These patients may already have had deep vein thrombi when they came on board, and the thrombi may have embolized to the lungs during the flight. These reports indicate that symptomatic PE during or immediately after airline flights is very rare and may or may not be related to the flight.
There is considerably more information available regarding the second scenario, which is far more common: venous thromboembolism (VTE) occurring after air travel. Homans,7 in 1954, was the first to report PE associated with air travel. He reported 2 cases after long air trips and an additional 2 cases associated with long automobile trips.
In 1977, Symington and Stack1 reported an association between travel and VTE. They reported that among 182 cases of VTE diagnosed in Glasgow, Scotland, over a 3-year period, 8 (4%) developed acute symptoms after a journey. The journeys lasted from 3 to 24 hours (average, 10 hours). Three journeys were by air, 3 by car, and 2 by rail. They did not report the prevalence of recent journeys in a control group. All of the patients were middle-aged or older, and 6 of the 8 had a history of venous disease. They attributed the venous thrombosis to stasis secondary to sitting and the pressure of the edge of the seat on the back of the calves. Symington and Stack1 noted that the term economy class syndrome has been used to describe venous problems associated with flying.
Subsequent to the report by Symington and Stack,1 4 case-control studies compared the prevalence of a history of recent travel in patients with VTE with a control group, as given in Table 1. Of the 4 studies,4,8-10 3 found a positive relationship between recent travel and VTE; the study by Kraaijenhagen et al9 did not find a relationship. In the 4 studies, a history of recent travel was present in 13.3% of the 1192 patients with VTE compared with 6.9% in the 1608 controls.
The clearest evidence that travel can increase the incidence of VTE comes from studies that have performed duplex ultrasonography of the legs before and after air travel (Table 2).
Schwarz et al,3 in this issue of the ARCHIVES, report the results of ultrasonography of the leg veins of 964 passengers performed before and after flights lasting longer than 8 hours and compared the findings with those in 1213 nonflying controls. The incidence of DVT in the passengers was 2.8% compared with 0.98% in the nonflying controls. Most thrombi were asymptomatic and limited to calf muscle veins.
Belcaro et al11 randomized 833 subjects at high risk of VTE to use or not use below-the-knee elastic stockings during flights (in economy class) of an average of 12 hours. The incidence of DVT in those not wearing stockings was 4.5% compared with 0.24% in those wearing elastic stockings. In a similar study, Scurr et al12 reported an incidence of asymptomatic calf vein DVT of 10% in 116 subjects randomized to a control group compared with no cases of DVT in passengers randomized to wear elastic stockings during flights of at least an 8-hour duration. The overall incidence of DVT after long-distance flights in the 1502 patients not wearing elastic stockings in these 3 studies3,11,12 was 3.9%.
The risk factors that lead to venous thrombosis in this setting have been described as being patient-related and cabin-related.13 Patient-related factors include older age and the presence of other risk factors for VTE. Most of the reported patients have been older than 50 years, and many have been reported to have been obese. As shown in Table 3, most patients with this syndrome had 1 or more risk factors for VTE. A history of venous disease is especially frequent; in 3 reports in which a history of VTE was assessed,1,3,14 34 (43%) of 79 patients had a history of VTE (Table 3).
Two reports in this issue of the ARCHIVES have studied the prevalence of thrombophilia in patients with VTE associated with air travel. Martinelli et al4 found that 18 of 31 patients with VTE associated with air travel had thrombophilia—most frequently factor V Leiden or hyperhomocystinemia. The odds ratio for VTE after air travel in patients with thrombophilia was 16.1 (95% confidence interval, 3.6-70.9) compared with those without thrombophilia and without air travel. In the report by Schwarz et al,3 20 of the 27 patients with VTE associated with air travel had a hypercoagulable state.
These reports make it clear that VTE after long air flights is most likely to occur in older flyers with a history of VTE and/or other risk factors for VTE. The reports by Martinelli et al4 and Schwarz et al3 in this issue of the ARCHIVES suggest that most of these patients may have thrombophilia, as first suggested by Homans7 in 1954.
A variety of cabin-related factors that have been suspected to predispose to VTE including hypoxia, low cabin humidity, dehydration, and smoking.6 However, the most frequently cited factor is prolonged sitting in cramped quarters. Nearly all reported cases have occurred in flights longer than 6 hours. It is believed that the prolonged immobility attendant to sitting as well as pressure on the calves by the passenger's seat can cause venous stasis leading to thrombosis. In the report by Lapostolle et al,5 53 of the 56 passengers who had PE reported that they never left their seat during the flight. Since seating in economy class is more cramped than in first class, passengers in economy class are more likely to remain seated throughout the flight. The term economy class syndrome seems appropriate. However, it should be noted that the reason that most of the reported cases of flight-related VTE have occurred in patients traveling in economy class is that most passengers fly in economy class!
Prolonged sitting, as first suggested by Homans,7 is clearly the key factor leading to VTE in patients who have risk factors for VTE, especially if they have thrombophilia.3,4,7 Prolonged sitting in crowded bomb shelters during the London Blitz during World War II was reported to be the cause of a significant increase in fatal PE.18 The increased PE deaths occurred in, or just after leaving, air raid shelters. Most had sat on deck chairs for many hours (often all night) for many nights. The author noted that the front edge of the chairs pressed into legs, compressing the veins. Most of the patients were older than 60 years, and many were reported to be obese.18
Naide,19 in 1952, reported an increased incidence of VTE in tall men (>6 feet [>180 cm]). He suggested that a contributing factor was "the cramped positions that tall persons are frequently forced to assume for considerable periods, especially when sitting." (The current reports of VTE associated with air travel do not report the patients' height!) Homans7 attributed the VTE associated with travel to prolonged sitting. He noted that "prolonged dependency stasis, a state imposed by airplane flights, automobile trips, and even attendance at the theater is able, unpredictably, to bring on thrombosis in the deep veins of the leg." He also suggested that thrombophilia may be a factor in these cases.
Dexter,20 in a 1972 article titled "The Chair and Venous Thrombosis," traced the history of chairs, "chair sitting," and venous thrombosis. He found that chair sitting and venous thrombosis appeared at about the same time in history. The first documented case of venous thrombosis was in the 13th century.21 Henry VIII of England's case of venous thrombosis in the 16th century was only the third known case. The chair came into use in Europe in the 16th century, but prolonged chair sitting was uncommon until the 20th century with the introduction of travel by automobile and air and the widespread adoption of a sedentary lifestyle characterized by prolonged sitting. Dexter20 speculated that the significant increase in the incidence of VTE in the 20th century can be attributed, in part, to a sedentary lifestyle leading to prolonged chair sitting. He noted that during chair sitting, the leg muscles remain immobile for minutes at a time leading to venous stasis, which may result in venous thrombosis with prolonged chair sitting.
The people who are at greatest risk of VTE with prolonged sitting are the elderly people and those with other risk factors for VTE. The people who are at the very highest risk are those with a history of VTE and those with thrombophilia. 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 train.
Recent studies suggest that VTE secondary to long air flights may be preventable. Two randomized studies11,12 have demonstrated a marked reduction in VTE in patients who wore below-the-knee elastic stockings during long flights (Table 2). One small study22 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 flights. The incidence of DVT was 4.8% in the control group. There were no cases in those randomized to low-molecular-weight heparin (P<.002).
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 thrombophilic. In addition to frequent ambulation during long journeys, those at increased risk of VTE may benefit from the use of elastic stockings.
Economy Class Syndrome: Too Much Flying or Too Much Sitting? Arch Intern Med. 2003;163(22):2674–2676. doi:10.1001/archinte.163.22.2674
Create a personal account or sign in to: