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

1

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.

2

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

3

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.

4

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

5

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.

1. 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.

2. 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

6

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.

3. Blood tests

o 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.

o 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

4. 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.

7

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

8

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

9

1.3.2 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

10

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.

11

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

12

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

external air at high altitude, which is sucked in, and compressed by the engines, before

13

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

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

14

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.

Table 3 Guidelines for Advice to Passengers

Complaint of leg edema without history of venous thrombosis

15

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

Reference

16

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.htm l

(Accessed on 14 January 2008)

17