John H Scurr, Samuel J Machin, Sarah Bailey-King, Ian J Mackie, Sally McDonald, Philip D Coleridge Smith
Summary Introduction
1–3
Background The true frequency of deep-vein thrombosis Every year the number of 4passengers
–6 travelling over long
(DVT) during long-haul air travel is unknown. We sought to distances by air increases. Physicians working close to
major airports have seen individual cases presenting
7 with
determine the frequency of DVT in the lower limb during long- thromboembolic problems after air travel. Results of
haul economy-class air travel and the efficacy of graduated retrospective clinical series suggest that up to 20% of
elastic compression stockings in its prevention. patients presenting with 8thromboembolism have
undertaken recent air travel. Ferrari et al reported a
Methods We recruited 89 male and 142 female passengers strong association between deep-vein thrombosis (DVT)
over 50 years of age with no history of thromboembolic and long travel (>4 h) in a case-control study, although
problems. Passengers were randomly allocated to one of only a quarter of his patients with DV T travelled by air.
two groups: one group wore class-I below-knee graduated Kraaijenhagen and colleagues looked at travel in the
elastic compression stockings, the other group did not. All previous 4 weeks in patients presenting with DVT. They
the passengers made journeys lasting more than 8 h per concluded that travelling times of more than 5 h were not
flight (median total duration 24 h), returning to the UK within associated with increased risk of DVT. The true 9,10
6 weeks. Duplex ultrasonography was used to assess the frequency of this problem remains unknown and
deep veins before and after travel. Blood samples were controversial. Episodes of D V T can arise without any
analysed for two specific common gene mutations, factor V symptom. Less
11,12 than half the patients with symptomless
Leiden (FVL) and prothrombin G20210A (PGM), which D V T will develop symptoms, and only a few of those go
predispose to venous thromboembolism. A sensitive D- on to have a clinically
13 detectable pulmonary embolism. In
dimer assay was used to screen for the development of surgical series, a link between symptomless DVT,
recent thrombosis. symptomatic DVT, and pulmonary embolism has been
established. Patients undergoing surgical procedures
Findings 12/116 passengers (10%; 95% CI 4·8–16·0%) are assessed for risk, and appropriate prophylaxis is
developed symptomless DVT in the calf (five men, seven implemented. We undertook a randomised controlled
women). None of these passengers wore elastic Correspondence to: Mr J H Scurr, Lister Hospital, Chelsea Bridge
compression stockings, and two were heterozygous for FVL. Road, London SW1W 8RH, UK
Four further patients who wore elastic compression
(e-mail: medleg@mailbox.co.uk)
stockings, had varicose veins and developed superficial
thrombophlebitis. One of these passengers was
heterozygous for both FVL and PGM. None of the
passengers who wore class-I compression stockings
THE LANCET • Vol 357 • May 12, 2001
developed DVT (95% CI 0–3·2%).
For personal use. Only reproduce with permission from The Lancet Publishing Group.
ARTICLES
compressed the calf and measured the duration of reverse 479 total population
flow by colour or pulsed doppler sonography. Venous considered
reflux was defined as duration of reverse flow exceeding
0·5 s. The presence of current or previous venous
thrombosis was assessed from the B-mode image, colour 248 excluded
flow mapping, and compression assessment of veins
during B-mode imaging. Passengers who had evidence of 231 randomised
previous thrombosis were excluded.
Trial profile
two groups. The control group received no specific of no case of venous thrombosis in this number of
additional treatment; the other group was given passengers would have resulted in a 95% CI for the rate
class-I (German Hohenstein compression standard; of D V T of 0 –2%. To measure a thrombotic event
20–30 mm Hg) below-knee elastic compression stockings occurring in 2% or fewer passengers would require a very
(Mediven Travel; Medi U K Ltd, Hereford, UK). large study, and the low frequency would have limited
Participants were advised to put on the stockings before implications for air travellers. Data were analysed by
the start of travel and to remove the stockings after arrival contingency tables and calculation of the differences in
for every flight by which they travelled. Although the proportions,and 95% CIs by a computer program (CIA
stockings were allocated randomly, the passengers were version 1.1, 1989, BMA Publishers, London, UK). We
aware of the treatment. Passengers arranged their own air used median and interquartile range for haematological
travel. There was no collaboration with the airlines, data since data were not normally distributed.
although two passengers were upgraded from economy to Haematological data were included in the analysis only
business class. when volunteers were examined before and after travel.
All other analyses were done on an intention-to-treat
basis, which included all randomised participants.
Evaluation Results
Passengers reattended the Stamford Hospital within 48 h Volunteers were excluded before randomisation if they did
of their return flight. They were interviewed by a research not fulfil the entry requirements or could not attend
nurse and completed a questionnaire inquiring about: hospital for investigation both before and after travel
duration of air travel, wearing of stockings, symptoms in (figure). Thus, 231 of 479 volunteers were randomised. 27
9
the lower limbs, and illnesses and medication taken passengers were unable to attend for subsequent ultrasound
during their trip. Most passengers removed their 9
investigation because of ill-health (three), change of travel
stockings on completion of their journey. The nurse plans, or inability to keep appointments (24). Two who
removed the stockings from those passengers who had
continued to wear them. A further duplex examination
was then undertaken with the technician unaware of the
group to which the volunteer had been randomised. Statistics Hours flying time
Another blood sample was taken for repeat D-dimer Haemoglobin (g/L)
assay. In passengers for whom clinically significant Because of Number
insufficient WBC ( 10 /L)
abnormalities of the lower limb veins were detected on Age (years)
duplex ultrasonography, including calf vein thrombosis, published data we Packed cell volume
could not pre- Number of women
the volunteers ’ general practitioners were notified in (%) Platelets ( 10 /L)
writing so that treatment could be arranged. calculate sample
size. Since the Number with Number FVL positive
varicose veins
investigation was Number PGM
Days of stay
positive No stockings Stockings
116 115
62 (56–68) 61 (56–66)
61 (53%) 81 (70%)
41 45
17 (13–32) 16 (13–27)
22 (18–36) 24 (19–35)
7 4
1 3
intended as a pilot study, we chose a total of 200 Median (interquartile range) shown, unless otherwise indicated. WBC=white blood cells.
FVL=factor V Leiden. PGM=prothrombin gene mutation.
passengers. Recruitment was continued until 100
volunteers had been investigated in each group. A finding Table 1: Characteristics of study groups
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ARTICLES
Volunteers grouped according to presence of symptomless deep vein thrombosis (DVT) and superficial thrombophlebitis (SVT). Median (interquartile range) shown, unless otherwise
indicated. WBC=white blood cells. FVL=factor V Leiden. PGM=prothrombin gene mutation. ND=not detectable (below the limit of sensitivity of the assay, 32 pg/L). *D-dimer values are
those individual values greater than 32 pg/L, all other passengers had concentrations less than 32 pg/L.
Table 2: Age and haematological data in 200 passengers examined before and after air travel
Leiden (11) or prothrombin gene mutation (four). One such as malignant disease or thrombophilia. We
person had both gene mutations and had an episode of excluded patients with a history of serious illness or
thrombophlebitis. Two passengers with symptomless DVT previous thrombotic episodes and all those with post-
were factor V Leiden positive. The full blood count, platelet thrombotic vein damage on duplex ultrasonography. We
count, and D-dimer assays provided no prognostic believe that the thrombi detected in our study were
attributable to long-haul air travel. Environmental
changes that take place during long-haul air travel may
Number of participants
No stockings Stockings provoke calf vein thrombosis. Once the journey has been
9 11 completed these factors no longer apply, allowing
Aspirin spontaneous resolution of calf vein thromboses without
8 16
Hormone replacement therapy complication in most cases.
6 6
Thyroxine In our study no symptomless D V T was detected in the
10 12
Antihypertensives, including diuretics stocking group. In hospital practice there is evidence that
8 3 graduated compression stockings are effective at reducing
Antipeptic ulcer drugs
Table 3: All drugs taken by volunteers who attended for the risk of D V T after surgical treatment. Our findings
examination before and after air travel* strongly suggest that stockings also protect against
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ARTICLES
References
reduce the occurrence of venous thrombosis—ie, by pr ence of D V T —were excluded, ensuring that no
being active during the flight and drinking more fluids. e bias resulted from this factor. However, the
We could not assess the effect that participation in the vi stocking group contained more women
21
study had on the behaviour of volunteers while aboard o
the aircraft. These factors would have applied equally to u
both our study groups. Whether leg exercises, walking, or s
drinking water prevent thrombotic events after airline hi 1488
travel remains to be established. st
or
The randomisation procedure was not stratified or y
miminised for any factor, since we regarded this study as of
a pilot investigation, which resulted in even distribution e
between the study groups for most factors. Volunteers vi
with the most important predisposition to DVT—a d
1 P staghorn stone. J Endourol 1998; 12: 51–53.
a
t Milne R. Venous thromboembolism and travel: is there an
e association? J R Coll Phys Lond 1992; 26: 47–49.
2 l
Sahiar F, Mohler SR. Economy class syndrome. Aviat Space Environ
3 A Med 1994; 65: 957–60.
,
4 Nissen P. The so-called “economy class”syndrome or travel
F thrombosis. Vasa 1997; 26: 239–46.
u
5
c Ribier G, Zizka V, Cysique J, Donatien Y, Glaudon G, Ramialison C.
h Venous thromboembolic complications following air travel.
s Retrospective study of 40 cases recorded in Martinique. Rev Med
Intern 1997; 18: 601–04.
G
6 J Eklof B, Kistner RL, Masuda EM, Sonntag BV, Wong HP. Venous
. thromboembolism in association with prolonged air travel. Dermatol
Surg 1996; 22: 637–41.
A
7 i Ferrari E, Chevallier T, Chapelier A, Baudouy M. Travel is a risk
r factor for venous thromboembolic disease: a case-control study. Chest
1999; 115: 440–44.
t
r
a
v
e THE LANCET • Vol 357 • May 12, 2001
l
a
n
d
t
h
r
o
m
b
o
e
m
b
o
l
i
c
c
o
m
p
l
i
c
a
t
i
o
n
s
a
f
t
e
r
p
e
r
c
u
t
a
n
e
o
u
s
n
e
p
h
r
o
l
i
t
h
o
t
o
m
y
f
o
r
For personal use. Only reproduce with permission from The Lancet Publishing Group.
ARTICLES
8 Kraaijenhagen RA, Haverkamp D, Koopman MMW, Prandoni P, 20 Bendz B, Rostrup M, Sevre K, Andersen T, Sandset PM. Association
Piovella F, Büller H. Travel and the risk of venous thrombosis. Lancet between acute hypobaric hypoxia and activation of coagulation in
2000; 356: 1492–93. human beings. Lancet 2000; 356: 1657–58.
9 Kakkar VV, Howe CT, Flanc C, Clarke MB. Natural history of 21 Nicolaides AN, Irving D. Clinical factors and the risk of deep vein
postoperative deep-vein thrombosis. Lancet 1969; 2: 230–32. thrombosis. In: Nicolaides AN, ed. Thromboembolism: aetiology,
10 advances in prevention and management. Lancaster: MTP, 1975:
Negus D, Pinto DJ. Natural history of postoperative deep-vein 193–203.
thrombosis. Lancet 1969; 2: 645.
11 Kniffin WD Jr, Baron JA, Barrett J, Birkmeyer JD,
22
Dalen JE, Alpert JS. Natural history of pulmonary embolism. Prog
12 Cardiovasc Dis 1975; 17: 259–70. Anderson FA Jr. The epidemiology of diagnosed pulmonary embolism
and deep venous thrombosis in the elderly. Arch Intern Med 1994; 154:
13 Coon WW. Epidemiology of venous thromboembolism. Ann Surg 861–66.
1977; 186: 149–64.
23 Robinson KS, Anderson DR, Gross M, et al. Accuracy of screening
TH R IFT Consensus Group. Risk of and prophylaxis for venous compression ultrasonography and clinical examination for the
14 thromboembolism in hospital patients. Thromboembolic Risk diagnosis of deep vein thrombosis after total hip or knee arthroplasty.
Factors. BMJ 1992; 305: 567–74. Can J Surg 1998; 41: 368–73.
Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal 24 Cornuz J, Pearson SD, Polak JF. Deep venous thrombosis: complete
pulmonary embolism and venous thrombosis by perioperative lower extremity venous US evaluation in patients without known risk
administration of subcutaneous heparin. Overview of results of factors—outcome study. Radiology 1999; 211: 637–41.
15 randomized trials in general, orthopaedic, and urologic surgery.
N Engl J Med 1988; 318: 1162–73. 25 Westrich GH, Allen ML, Tarantino SJ, et al. Ultrasound screening
for deep venous thrombosis after total knee athroplasty. 2-year
16
Kazmers A, Groehn H, Meeker C. Acute calf vein thrombosis: reassessment. Clin Orthop 1998; 356: 125–33.
outcomes and implications. Am Surg 1999; 65: 1124–27.
Forbes K, Stevenson AJ. The use of power Doppler ultrasound in the
26
O’Shaughnessy AM, Fitzgerald DE. The value of duplex ultrasound diagnosis of isolated deep venous thrombosis of the calf. Clin Radiol
17 1998; 53: 752–54.
in the follow-up of acute calf vein thrombosis. Int Angiol 1997; 16:
142–46.
Mantoni M, Strandberg C, Neergaard K, et al. Triplex US in the
27 diagnosis of asymptomatic deep venous thrombosis. Acta Radiol
Meissner MH , Caps M T , Bergelin RO, Manzo RA, Strandness DE
18 Jr. Early outcome after isolated calf vein thrombosis. J Vasc Surg 1997; 38: 327–31.
1997; 26: 749–56.
Robertson PL, Goergen SK, Waugh JR, Fabiny RP. Colour-assisted
Colditz GA, Tuden RL, Oster G. Rates of venous thrombosis after 28 compression ultrasound in the diagnosis of calf deep venous
19 general surgery: combined results of randomised clinical trials. Lancet thrombosis. Med J Aust 1995; 163: 515–18.
1986; 2: 143–46.
Krunes U, Teubner K, Knipp H, Holzapfel R. Thrombosis of the
Bounameaux H, de Moerloose P, Perrier A, Reber G. Plasma 29 muscular calf veins-reference to a syndrome which receives little
measurement of D-dimer as a diagnostic aid in suspected venous attention. Vasa 1998; 27: 172–75.
thromboembolism: an overview. Thromb Haemost 1994; 71: 1–6.
THE LANCET • Vol 357 • May 12, 2001 1489
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