THE ECONOMY CLASS SYNDROME

Introduction
Air travel is associated with a risk of deep vein thrombosis and pulmonary embolism,
which may be fatal. The exact incidence of thromboembolism in relation to air travel is
uncertain, though it has been estimated that at least 5% of all cases of deep venous
thrombosis may be linked to air travel. The term “economy class syndrome” has been
coined to describe the phenomenon, and this also emphasizes the role of impairment of
venous circulation due to prolonged immobility in a cramped position, in the
pathogenesis of the thrombosis.1
The mechanism for thrombosis in travelers is probably due to a combination of
immobilization, dehydration and underlying factors. Patients with disease that
predisposes them for thrombosis, such as antiphospholipid syndrome or cancer, are
probably at a much greater risk. The highest risk groups include the elderly, pregnant
women, those suffering serious medical conditions such as cancer and those with recent
orthopedic surgery (legs or knees).
Prevention consists of adequate hydration (drinking, abstaining from alcoholic
beverages and caffeine), moving around and calf muscle exercises. In patients with a
known predisposition for thrombosis, aspirin is often prescribed, as this acts as a mild
anticoagulant. Severe risk for thrombosis can prompt a physician to prescribe injections
with low molecular weight heparin (LMWH), a form of prophylaxis already in common
use in hospital patients.
There is clinical evidence to suggest that wearing compression socks whilst
travelling also reduces the incidence of thrombosis in people on long haul flights. A
randomised study in 2001 compared two sets of long haul airline passengers, one set
wore MediUK mediven travel compression hosiery the others did not. The passengers
were all scanned and blood tested to check for the incidence of DVT. The results showed
that asymptomatic DVT occurred in 10% of the passengers who did not wear
compression socks. The group wearing compression had no DVTs. The authors
concluded that wearing elastic compression hosiery reduces the incidence of DVT in long
haul airline passengers.2

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 CHAPTER 1
Economy Class Syndrome

1.1 Definition
The economy class syndrome is the occurrence of deep vein thrombosis in air travelers.
The term was first coined in the late 1980s when it turned out that people who had
traveled long distances by airplane were at an increased risk for thrombosis, especially
deep venous thrombosis and its main complication, pulmonary embolism. Although all
these diseases had been recognized for a long time, the possibility of litigation against
airline companies brought them into the limelight when this "syndrome" was reported.2

1.2 Deep Venous Thrombosis (DVT)

Deep Vein Thrombosis (DVT) is a thrombus formation in a deep vein of the body. They
commonly inhabit the femoral vein. Patients presenting with symptoms of a DVT are
considered high-risk patients because of the sequelae that may follow. 3
Venous clots most often occur in the deep veins of the leg which is called deep
vein thrombosis (DVT), or deep vein clot. Venous thrombosis in the lower limbs can be
confined to the superficial leg veins, or may extend to involve the deep veins of the calf,
or the more proximal veins such as the superficial femoral, common femoral, or even the
iliac veins. Thrombosis is significantly more common in the left leg, probably due to the
fact that the femoral artery on that side passes anterior to the vein and may compress it.
Thrombosis in the superficial veins of the legs often occurs in varicosities, but is usually
self-limiting. By contrast, the risk of pulmonary embolism is much higher when proximal
veins are involved. 4
Three predisposing factors are always present in the development of DVT, known
as Virchow’s Triad: vessel wall injury, blood stasis, and hypercoagulability.
Damaged endothelium may be caused by direct trauma, infections of surrounding
soft tissue, intravenous catheters or prolonged use of them. The trauma reveals
subendothelial tissue which releases platelet activating factors, initiating coagulation
cascade, results in platelet adhesion to the wall and the beginning of thrombus formation.

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 Blood stasis in the veins interferes with nutrition to the endothelial lining,
rendering the wall susceptible to minute thrombus formation. Causes of venous stasis are
immobilization or inactivity, typically following a stay in hospital, long plane flight,
application of a cast, illness, or caused by poor deep venous muscle pump from
apropulsive gait. Stasis may also be caused by sluggish or impaired venous return to the
heart following CVA, congestive heart failure, myocardial infarct, and valvular
incompetence.
Hypercoagulability of blood may be caused by haematological conditions such as
anaemia and polycythemia vera, through infectious disease such as typhoid and
pneumonia, as a secondary complication to nephrotic disease, or hypercoagulable drugs
and oral contraceptives. 3

Fig 1: Deep Vein Thrombosis (DVT of the Leg

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1.2.1 Sign & Symptoms 5
There may be no symptoms referable to the location of the DVT, but the classical
symptoms of DVT include pain, swelling and redness of the leg and dilation of the
surface veins. In up to 25% of all hospitalized patients, there may be some form of DVT,
which often remains clinically inapparent (unless pulmonary embolism develops).
There are several techniques during physical examination to increase the detection
of DVT, such as measuring the circumference of the affected and the contralateral limb at
a fixed point (to objectivate edema), and palpating the venous tract, which is often tender.
Physical examination is unreliable for excluding the diagnosis of deep vein thrombosis.
In phlegmasia alba dolens, the leg is pale and cool with a diminished arterial pulse
due to spasm. It usually results from acute occlusion of the iliac and femoral veins due to
DVT. In phlegmasia cerulea dolens, there is an acute and nearly total venous occlusion of
the entire extremity outflow, including the iliac and femoral veins. The leg is usually
painful, cyanosed and oedematous. Venous gangrene may supervene.
It is vital that the possibility of pulmonary embolism be included in the history, as
this may warrant further investigation (see pulmonary embolism). A careful history has to
be taken considering risk factors (see below), including the use of estrogen-containing
methods of hormonal contraception, recent long-haul flying, and a history of miscarriage
(which is a feature of several disorders that can also cause thrombosis). A family history
can reveal a hereditary factor in the development of DVT.

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 Fig 2: DVT with phlebitis in the leg

1.2.2 Etiology 5
Virchow's triad is a group of 3 factors known to affect clot formation: rate of flow, the
consistency (thickness) of the blood, and qualities of the vessel wall. Virchow noted that
more deep venous thrombosis occurred in the left leg than in the right and proposed
compression of the left common iliac vein by the overlying right common iliac artery as
the underlying cause (see May-Thurner syndrome).
The most common risk factors are recent surgery or hospitalization. 40% of these
patients did not receive heparin prophylaxis. Other risk factors include advanced age,
obesity, infection, immobilization, female sex, use of combined (estrogen-containing)
forms of hormonal contraception, tobacco usage and air travel ("economy class
syndrome", a combination of immobility and relative dehydration) are some of the better-
known causes. Thrombophilia (tendency to develop thrombosis) often expresses itself
with recurrent thromboses.
It is recognized that thrombi usually develop first in the calf veins, "growing" in
the direction of flow of the vein. DVTs are distinguished as being above or below the

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popliteal vein. Very extensive DVTs can extend into the iliac veins or the inferior vena
cava. The risk of pulmonary embolism is higher in the presence of more extensive clots.

1.2.3 Diagnosis 5
The gold standard is intravenous venography, which involves injecting a peripheral vein
of the affected limb with a contrast agent and taking X-rays, to reveal whether the venous
supply has been obstructed. Because of its invasiveness, this test is rarely performed.
Physical examination
• Homan's test: Dorsiflexion of foot elicits pain in posterior calf. However, it must
be noted that it is of little diagnostic value and is theoretically dangerous because
of the possibility of dislodgement of loose clot.
• Pratt's sign: Squeezing of posterior calf elicits pain.
However, these medical signs do not perform well and are not included in clinical
prediction rules that combine best findings in order to diagnose DVT.
Probability scoring
In 2006, Scarvelis and Wells overviewed a set of clinical prediction rules for DVT, on the
heels of a widely adopted set of clinical criteria for pulmonary embolism.
Wells score or criteria: (Possible score -2 to 9)
1) Active cancer (treatment within last 6 months or palliative) -- 1 point
2) Calf swelling >3 cm compared to other calf (measured 10 cm below tibial
tuberosity) -- 1 point
3) Collateral superficial veins (non-varicose) -- 1 point
4) Pitting edema (confined to symptomatic leg) -- 1 point
5) Swelling of entire leg - 1 point
6) Localized pain along distribution of deep venous system -- 1 point
7) Paralysis, paresis, or recent cast immobilization of lower extremities -- 1 point
8) Recently bedridden > 3 days, or major surgery requiring regional or general
anesthetic in past 12 weeks -- 1 point
9) Previously documented DVT -- 1 point
10) Alternative diagnosis at least as likely -- Subtract 2 points

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 Interpretation:
Score of 2 or higher - deep vein thrombosis is likely. Consider imaging the leg
veins.
Score of less than 2 - deep vein thrombosis is unlikely. Consider blood test such
as d-dimer test to further rule out deep vein thrombosis.
Blood tests
D-dimer
In a low-probability situation, current practice is to commence
investigations by testing for D-dimer levels. This cross-linked fibrin degradation
product is an indication that thrombosis is occurring, and that the blood clot is
being dissolved by plasmin. A low D-dimer level should prompt other possible
diagnoses (such as a ruptured Baker's cyst, if the patient is at sufficiently low
clinical probability of DVT.
Other blood tests
Other blood tests usually performed at this point are
• complete blood count
• Primary coagulation studies: PT, APTT, Fibrinogen
• liver enzymes
• renal function and electrolytes
Imaging the leg veins
Impedance plethysmography, Doppler ultrasonography, compression ultrasound scanning
of the leg veins, combined with duplex measurements (to determine blood flow), can
reveal a blood clot and its extent (i.e. whether it is below or above the knee). Duplex
Ultrasonography,due to its high sensitivity, specificity and reproducibility, has replaced
venography as the most widely used test in the evaluation of the disease. This test
involves both a B mode image and Doppler flow analysis.

As mentioned above, the sequelae following DVT may cause serious

complications, including sudden death. The most important of these is when part of the
thrombus breaks off to form an embolism, which can lodge in a lung and give rise to
pulmonary embolism.

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1.3 Pulmonary Embolism 4
A pulmonary embolism (PE) is a blood clot that develops in a blood vessel elsewhere in
the body (most commonly from the leg), travels to an artery in the lung, and forms an
occlusion (blockage) of the artery. An embolism to the lung may cause serious life-
threatening consequences and, potentially, death. Most commonly, a PE is the result of a
condition called deep vein thrombosis (blood clot in the deep veins of the leg).
The heart, arteries, capillaries, and veins make up the body's circulatory system.
Blood is pumped with great force from the heart into the arteries, then into the capillaries
(small blood vessels in the tissues) and returns to the heart through the veins. Much of the
force of the heartbeat is lost when the blood enters the veins and results in the slowing
down of the blood flow through the veins back to the heart. Under certain conditions,
decreased blood flow may contribute to clot formation.
As we know venous clots most often occur in the deep veins of the legs. Once a
clot has formed in the deep veins of the leg, there is a potential for part of the clot to
break off and travel (embolize) through the bloodstream to another area of the body.
Deep vein thrombosis is the most common cause of a pulmonary embolism. Therefore,
the term venous thromboembolism (VTE) may refer to deep vein thrombosis and/or the
complication, pulmonary embolism.
Other less frequent sources of pulmonary embolism are a fat embolus, amniotic
fluid embolus, air bubbles, and a deep vein thrombosis in the upper body. Clots may also
form on the end of an indwelling intravenous (IV) catheter, break off, and travel to the
lungs.

1.3.1 Risk Factors 6

Risk factors that are associated with the processes that may increase the risk of a venous
thromboembolism include:
• genetic conditions that increase the risk of blood clot formation
• surgery or trauma (especially to the legs)
• situations in which mobility is limited, such as extended bed rest, flying or riding
long distances, or paralysis
• previous history of clots

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• older age
• cancer and cancer therapy
• certain medical conditions, such as heart failure, chronic obstructive pulmonary
disease (COPD), hypertension (high blood pressure), stroke, and inflammatory
bowel disease (chronic inflammation of the digestive tract)
• certain medications, such as oral contraceptives (birth control pills) and hormone
replacement therapy (estrogen pills for postmenopausal women)
• pregnancy (during and after pregnancy, including cesarean section)
• obesity
• varicose veins (enlarged veins in the legs)
• cigarette smoking

Fig 3: Pulmonary Embolism

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Symptoms 7
The following are the most common symptoms for pulmonary embolism.
• sudden shortness of breath (most common)
• tachypnea (rapid breathing)
• chest pain (usually worse with breathing)
• a feeling of anxiety
• a feeling of dizziness, lightheadedness, or fainting
• palpitations (heart racing)
• coughing up blood (hemoptysis)
• sweating
• symptoms of deep vein thrombosis, such as:
o pain in the affected leg (may occur only when standing or walking)
o swelling in the leg
o soreness, tenderness, redness, and/or warmth in the leg(s)
o redness and/or discolored skin
• may be associated with cyanosis (blue discoloration, usually of the lips and
fingers)
• collapse
• circulatory instability.
About 15% of all cases of sudden death are attributable to PE. The type and extent of
symptoms of a pulmonary embolism will depend on the size of the embolism and
whether the person already has existing heart and/or lung problems.

1.3.3 Pathology 8
• Large or small blood clots may occlude major or minor branches of the
pulmonary arterial circulation.
• Large emboli may cause acute cor pulmonale. Saddle thrombus is a blood clot
which is seen at the bifurcation of the pulmonary artery. This could result in
sudden death with no pathologic change in the lungs

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 • Smaller emboli lodge distally depending on their size. There is hemorrhage into
the adjacent lung parenchyma Ten percent of emboli cause wedge-shaped
hemorrhagic infarctions which extend to the peripheral lung.
• Infarction occurs when there is underlying heart failure or other diseases causing
inadequacy of bronchial arterial supply. Infarcts are typically pyramidal with base
at the pleura. The lung parenchyma dies (there are no nuclei in the septa) and
there is often hemorrhage into the infarcted lung tissue If the cardiovascular
function is adequate, the bronchial circulation will maintain tissue viability
resulting in hemorrhage but no infarct.

1.4 Air Travel and Thrombosis 1

There are many published reports which link venous thromboembolism with air travel.
The first report concerned that of a physician who traveled from Boston to Venezuela in
1946 on a nonstop flight lasting 14 hours. The development of thrombosis in the setting
of flight has been euphemistically termed the “economy class syndrome,” reflecting the
importance of sitting for long periods in cramped conditions in the pathogenesis.
However, venous thrombosis is not exclusively associated with air travel; it has also been
documented following long car, bus or even train journeys.
During periods of extended inactivity in cramped conditions such as a long plane
flight or even a long car ride, normal blood circulation can be restricted. This can cause
leg fatigue and discomfort and may contribute to the serious problem of Economy Class
Syndrome or DVT. Activity of the calf muscles is needed to contract veins and propel
blood from the legs back to the heart. Without this activity, blood can pool in the veins of
the leg and form DVT, a blood clot in the legs. The problem may not be obvious until a
traveler arrives and begins normal activity. That's when the clot can dislodge and migrate
to the lungs where it can cause a pulmonary embolism, a dangerous and often deadly
condition.

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 Fig 4 : Thromboembolism in Air traveler

A case-controlled study from France reported a history of recent travel (with a

journey exceeding 4 hours) in 39 of 160 patients with thromboembolism of whom 9 had
flown, 2 had traveled by train and 28 by car. Furthermore, thrombosis is by no means
restricted to those in the relatively confined conditions of economy class, and thus the
alternative term of “travelers’ thrombosis” has been suggested. The risk of
thromboembolism associated with confinement in cramped conditions has been
recognized for some years.
Simpson, the distinguished forensic pathologist, noted a rise in the incidence of
sudden death from pulmonary embolism associated with the onset of the night bombing
raids on London at the beginning of the Second World War. These deaths usually
occurred in elderly people who had spent a night sleeping uncomfortably in deck chairs,
in an air raid shelter. Simpson recognized that the primary cause was mechanical

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impairment of venous circulation due to squatting for a prolonged period, and he
recommended that bunks should be installed in the shelters.
The incidence of symptomatic venous thromboembolism in association with air
travel is low, although no prospective studies have been conducted to quantify the risk
with precision. However, even though the risk is low, the sheer numbers of passengers
traveling magnifies the effect so that significant numbers of cases will be encountered in
clinical practice. Two studies from Hawaii, a destination accessible only by air, with a
typical journey time of over 5 hours, uncovered air travel as a risk factor in 44 of 254
(17%) patients with thromboembolism in one study and in 33 of 134 (24%) in the other.
Most reports involve venous thrombosis in the lower limbs, but there are also reports of
cerebral venous thrombosis, and arterial thrombosis, associated with long flights.
It is possible to derive some general conclusions from a survey of published cases.
Thromboembolism is rarely observed after flights of 5 hours duration, and typically the
flights are of 12 hours duration or more. The risk rises with age, and older subjects over
the age of 50, are more at risk, while those under the age of 40 years, are less vulnerable.
Symptoms of thromboembolism do not usually develop during, or immediately after the
flight, but more typically appear within 3 days of arrival, when the patient may present
far away from the airport, and thus the causal link may not be immediately apparent.
Symptoms of thrombosis or pulmonary embolism have been reported up to 2 weeks after
a long flight. Pulmonary embolism may also be the first manifestation, without any
symptoms in the lower limbs. In a study of 61 cases of sudden death in airline passengers
on flights arriving at Heathrow airport in London between 1979 and 1982, pulmonary
embolism was identified as the cause at autopsy in 11 (18%) cases. Ten cases had
involved flights of longer than 12 hours duration.

1.4.1 Specific Risk Factors

There are also specific risk factors to air travel, including relative immobility for a
prolonged period in a cramped position. Both unusually tall, and short individuals, are
particularly vulnerable. Most airline seats have fairly rigid metal frames designed for
safety in the event of an accident, but the metal bar at the front edge may compress the
popliteal vein. Dehydration is also a problem, as cabin air is derived from the cold, dry

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external air at high altitude, which is sucked in, and compressed by the engines, before
being pumped into the cabin, after heating. Excessive consumption of alcohol will also
contribute to the development of dehydration through its diuretic effect, and the sedative
effect will also encourage immobility.

1.4.2 Prevention
A number of general measures may be taken to minimize the risk of thrombosis
associated with long air journeys. Adequate hydration should be ensured during the
flight. It is not necessary to abstain from alcohol, but excessive consumption should be
avoided, as this will both promote diuresis, and discourage mobility. Simple stretching
exercises during flight, such as flexion and extension of the ankles, will help to promote
circulation in the lower limbs, and occasional short walks in the cabin are recommended.
Deep breaths assist the venous return, and the pulmonary circulation. Although, in
recent years, the pitch of some aircraft seats has been increased, and adjustable foot rests
have been installed, mobility is still restricted. An aisle seat or one next to an exit offers
more space, although the latter are usually only allocated to able-bodied individuals in
case passenger assistance is required to open doors in the event of an emergency. Hand
luggage stowed under seats will also restrict movement.
In the absence of randomized controlled studies, it is not possible to give
evidence-based recommendations regarding prophylactic treatment to prevent
thromboembolism, but nevertheless some conclusions may be drawn from experience in
other settings . For people regarded to be at risk of thrombosis, the wearing of elasticated
stockings on both legs may be helpful, and these are cheap and readily available without
prescription. The stockings should extend above the knee, and care should be taken to
ensure that they do not slip and cause constriction in the popliteal area.
Quite apart from reducing the risk of thrombosis, elasticated stockings help to
prevent edema in the legs and feet, which can itself cause discomfort. Since major
surgery, particularly orthopedic, is a well recognized risk factor for thrombosis, it may be
advisable to postpone nonessential journeys immediately after such an operation. For
individuals with a definite thrombotic risk, for example a history of thrombosis and an
identified thrombophilic defect such as protein C deficiency, it would be prudent to get a

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single injection of low molecular weight heparin by subcutaneous injection, immediately
before the flight. The precise dose varies according to the particular product used, but a
suitable prophylactic dose of dalteparin is 2,500 units by subcutaneous injection, 1 or 2
hours before flight. Care should be taken to avoid inadvertent intramuscular injection, as
this is likely to result in the formation of a significant hematoma. Heparin should not be
used when there is a pre-existing hemorrhagic condition (e.g., thrombocytopenia), or
other medical condition where there is a potential for bleeding (e.g., peptic ulceration).
Stockings, of course, represent a perfectly safe alternative in such cases.
The use of aspirin has been advocated for general prophylaxis by some. Aspirin is
certainly a potent anti-platelet agent, and has a definite role in preventing thrombosis in
the arterial tree (such as transient ischemic attacks, or myocardial infarction). However,
platelets play only a minor role in the development of venous thrombosis. A meta-
analysis of 55 clinical studies involving some 8,500 patients showed that aspirin is of
some prophylactic value, and reduced the risk of venous thromboembolism by around
25% in a predominantly surgical setting.
This degree of risk reduction is certainly significant, but is considerably less than
can be achieved with heparin, or even compression stockings. A more recent, and larger
prospective study, demonstrated a similar reduction in the incidence of venous
thromboembolism, when aspirin was used in the setting of hip fracture during major
orthopedic surgery. On balance, a single aspirin tablet taken prior to a long flight may be
of some prophylactic value and is primarily suitable for individuals with no documented
high-risk factors.
Aspirin, in contrast to warfarin, is not contraindicated for flight crew. Aspirin is
certainly not contraindicated in subjects already using low doses of heparin for
thromboprophylaxis, but the combination is probably best avoided in this setting, in order
to avoid the potential for hemorrhagic complications.
Elasticated stockings, or low molecular weight heparin, should be considered by
individuals considered to be at moderate or high risk of thromboembolism, by virtue of
their medical history.

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Table 3 Guidelines for Advice to Passengers
Complaint of leg edema without history of venous thrombosis
1. Exercise legs (including walking around the cabin) and deep breathing at regular
intervals.
2. Keep well hydrated using clear fluids.
3. Avoid excessive alcohol.
4. Avoid sleeping in an uncomfortable position, especially with hypnotics.
5. Consider use of low compression stockings.

History of previous venous thrombosis and/or thrombophilia.

Prophylactic measures to be considered for long haul flights:
1. Aspirin.
2. Bilateral stockings covering foot to above knee.
3. Low molecular weight heparin before flight.

Recent surgery/injury to lower limbs Advise patient to avoid journey.

If not, prophylaxis essential in view of high risk.

Fig 5: Simple stretching exercises during flight

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 Reference

1. Paul L.F. Giangrande. 2000, Jurnal Travel Medicine, Thrombosis and Air Travel.
P 149 – 154.
2. Gorlin R. Economy Class Syndrome. 5 September 2007. Available at:
http://en.wikipedia.org./wiki/Economy_Class_Syndrome.html. (Accessed on 14
January 2008)
3. Smith Jr. Deep Venous Thrombosis (DVT). 24 October 2001. Available at:
http://en.latrobeuniversity.org./latrobe/Deep_Venous_Thrombosis.html.
(Accessed on 14 January 2008)
4. Richard Shepherd 2003, Simpson’s Forensic Medicine, Unexpected and Sudden
Death from Natural Causes. P126
5. Jeremy F. Pulmonery Embolism. 10 January 2007. Available at:
http://www.meghealth.org/greystone/heart/pulembo.html. (Accessed on 14
January 2008)
6. Jeremy F. Pulmonery Embolism. 10 January 2007. Available at:
http://www.meghealth.org/greystone/heart/pulembo.html. (Accessed on 14
January 2008)
7. Doucette S. Deep vein thrombosis. 3 January 2008. Available at:
http://en.wikipedia.org/wiki/Deep_vein_thrombosis. (Accessed on 14 January
2008)
8. Fergusson D. Pathology of Pulmonary Embolism. 7 July 2004.
http://www.meddean.luc.edu/lumen/Meded/elective/pulmonary/pe/pe.html
(Accessed on 14 January 2008)

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