FLIGHT RELATED DEEP VEIN THROMBOSIS  

SMJ 2002: 47(6) 123-126

  Justin MC Yeung BMedSci, BMBS, MRCS(Ed)  Specialist Registrar in General Surgery

  Krishna Lingam MBCHB(Glas), MD(Glas), FRCS(Glas) Consultant Vascular Surgeon

  Department of Vascular Surgery, Derbyshire Royal Infirmary, UK. DE1 2QY

Correspondence and requests for reprints:-

Mr Justin MC Yeung

Division of Vascular Medicine

Derbyshire Royal Infirmary

DE1 2QY

Tel +44 (01332) 254966

Fax +44 (01332) 254968

justinyeung@doctors.org.uk

Source of Support:- Nil

Abstract

Background:                

Flight Related Deep Vein Thrombosis (DVT) is a potentially life threatening condition. It is more commonly known as the Economy Class Syndrome as it has been linked to the lack of space within the Economy Class Cabin. Millions of people travel by air each year and yet relatively very few people are aware of its aetiology and methods of prevention.

Aims:               

This review article aims to provide background information on DVT and its relationship with flight travel. It also highlights the current available methods of diagnosis, treatment and prevention.

Methods:           

Medline search of articles centred on Economy Class Syndrome, DVT, and Pulmonary Embolus.

Results:           

Although the incidence of symptomatic DVT occurs in 1:2000 within the general population, patient factors such as thrombophilia and hormonal therapy increase this risk.  More importantly, air travelers are at greater risk because of immobility and compression of the venous system; dehydration related to the dry cabin atmosphere and diuretic substances like caffeine and alcohol; and finally decreased air pressure and cabin hypoxia which lead to a reduced fibrinolytic activity and stimulation of the coagulation cascade. 

Conclusion:           

The term Economy Class Syndrome should be renamed Flight Related Deep Vein Thrombosis as it can occur in any passenger irrespective of class.

  Key Words:-            Flight Related DVT, Economy Class Syndrome, Deep Vein Thrombosis

Introduction:

Deep vein thrombosis related to air travel received media attention when several young fit individuals died from pulmonary embolism secondary to deep vein thrombosis associated with long haul travel.  The possible link between deep vein thrombosis and air travel is not new. It was first put forward by Homan in1954 when he reported a case of a doctor who developed deep vein thrombosis after a long haul flight ¹. He went on to postulate that any activity that involved immobility for a long length of time would predispose to the development of deep vein thrombosis. He included airplanes flights, automobile travel and even a visit to the theatre! Symington and Stack coined the term ‘Economy Class Syndrome’ in 1977 ². In their retrospective study of 183 cases of pulmonary embolism, eight patients gave a history of recent travel. In these eight patients, three had travelled by air and were all in the economy class. They proposed that passengers travelling in the economy class had the added disadvantage of having to travel in a cramped “coach” position with restricted legroom when compared to the business class or first class travel. They suggested that deep vein thrombosis affected travellers only in the economy class where they had to travel in this cramped position and therefore called it the Economy Class Syndrome. It is interesting to note that a similar syndrome had been described during the Blitz where people sitting in air raid shelters for long periods of time, developed pulmonary emboli ³. The term economy class syndrome is misleading as this implies that it affects only economy class passengers. This however is not true as there have recently been cases of deep vein thrombosis even in first class passengers. The term economy class syndrome should not be used and instead the term Flight Related Deep Vein Thrombosis or Traveller-Related Deep Vein Thrombosis should be used. There is currently only circumstantial evidence and no epidemiological evidence to support the link between air travel and deep vein thrombosis. There is no information on how common is travel related deep vein thrombosis, what the risk factors are and how it can be prevented. What is known though is that deep vein thrombosis may be associated with any long distance travel whether by car, air, coach or train. This risk may be increased in long haul flights where passengers remain immobile in seated position for long periods of time.

Incidence of Deep Vein Thrombosis

Heathrow Airport is the world's busiest airport with over 62 million passengers passing through it last year ⁴.  The relationship between air travel and DVT is only based on circumstantial evidence with no real epidemiological evidence available ⁵.  Retrospective studies have suggested up to 20% of patients diagnosed with thromboembolism have had a history of recent air travel. In one case, a retrospective study of 254 patients admitted from 1988 to 1993 under the diagnosis of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) identified 44 with a history of recent air travel ^6,7,8. 

When we look at a wider picture, the annual incidence of deep vein thrombosis within the UK is also difficult to quantify, as many patients are asymptomatic with relatively small venous thrombi.  We do however know with respect to hospital patients that in 30% of all general surgical patients without any DVT prophylaxis and in 70% of all orthopaedic patients without prophylaxis develop a DVT ^9,10,11,12. In order to obtain a rough estimate of the incidence of DVTs, we need to extrapolate using known data on pulmonary embolism. To make sense of the calculation, we need to understand that it is the development of a PE following a DVT, which causes significant morbidity and mortality.  We know that approximately 20,000 patients with symptomatic PE die each year in the United Kingdom ¹³.  This is only approximately 10% of all symptomatic pulmonary emboli and therefore this means there are 200,000 symptomatic PE’s per year within the UK ^{14, 15}.  We also know that about 15-20% ^16,17 of DVT’s lead to a symptomatic PE and therefore extrapolating from this there is a potential incidence of 1 million DVT’s per annum.  This is a striking figure when one considers the total population within the UK is only 65million. What is known though is that the incidence of symptomatic DVT occurs in about 1 in 2000 in the general population ¹⁸. Scurr et al. ¹⁹ performed a prospective study where they recruited a total of 231 patients (89 male and 142 female) who were taking an eight-hour long haul airplane trip.  50% of them were given knee-high stockings and the other 50% were not given any anti-thrombotic measures.    Prior to their airplane journey, they had duplex scan of their venous system carried out and a similar exercise carried out after the return leg of their journeys. The findings were quite startling in that in the group of patients that did not have stockings, 12 developed symptomless DVTs whereas in the group that wore the stockings there were no incidence of DVTs.

Pathophysiology of Flight Related Deep Vein Thrombosis

The development of the Flight Related Deep Vein Thrombosis is multifactorial.  Venous thrombi are formed by stasis and are mainly composed of red blood cells intertwined with fibrin.  As very few platelets are involved, drugs that affect platelet function are less effective for DVT prophylaxis. The likely sequence of development of flight related DVT in susceptible individuals are as follows. The cramped coach position of the air traveller causes compression of the popliteal vein. Secondly the immobility causes decreased amount of activity thereby a reduction in the muscle pump function ²⁰.  Both these factors increase the likelihood of stasis.  The dry atmosphere within the air cabin coupled with a decreased fluid intake causes a haemoconcentration. Consumption of alcohol and caffeine lead to diuresis, which further compounds the problem of heamoconcentration in the blood. The final insult is brought about by decreased air pressure and the presence of cabin hypoxia (due to the fact that air within the cabin is recycled). This leads to a reduced fibrinolytic activity, an increased release of vein wall relaxin factors, promoting venous stasis, and finally leading to an increased stimulation of the coagulation cascade ²¹.

 Who are at risk of developing Flight Related Deep Vein Thrombosis?

In the general population, the risk of developing deep vein thrombosis and pulmonary thromboembolism are listed on Table 1. These groups make up to 90 to 95% of all those who get DVT and/or PE.  Again there are no epidemiological studies of risk factors. While it is difficult to be certain, the lack of exercise or immobility is thought to be the major underlying risk factors. It is difficult to say whether the flight itself caused deep vein thrombosis or whether these people were already at risk due to other factors as DVT is a common condition and that more people than ever travel by air every year. The recent document on travel related deep vein thrombosis (DVT) released by the Department of Health has emphasized the risk for women who are on hormonal treatment such as the oral contraceptive pill and HRT ¹⁸. What it also stresses is that the vast majority of air passengers do not need to take any medication to prevent DVT formation and those who are at greatest risk, can simply reduce their chances by following exercises documented in their article. Significant risk factors for Flight Related DVT include a previous deep vein thrombus as well as a history of taking the oral contraceptive pill (OCP). There has been some evidence for an interaction between combined OCPs and the factor V Leiden mutation leading to a higher risk of venous thromboembolism in women who have this heritable thrombophilic defect ²². In Caucasian populations, factor V Leiden is very prevalent, being present in between 3% and 7% of Europeans and white North Americans ²². Hormone replacement therapy increases this risk especially if there is a previous DVT history ²³.  Patients with a history of malignancy have a higher risk and indeed deep vein thrombosis may be an early presentation of malignancy. Blood coagulation is activated by tissue factor and cancer procoagulants that are expressed in the cancer cells. Other factors, which activate cells like monocytes and endothelial cells, include cytokines. Activated coagulation predisposes to venous thrombosis ²⁴. Briefly mentioned is the concept of inherited hypercoagulable conditions. These include genetic mutations like protein C and protein S, Factor V Leiden and factor II G20210 A ^25,26. Serum risk indicators, such as hyperhomocysteinemia have also been documented ²⁷. Recent surgery including abdominal, pelvic and orthopaedic surgery, or immobility due to conditions such as stroke also predispose to venous stasis.  Finally, less obvious but equally important is that varicose veins can increase the risk of developing DVT due to reflux and the stasis of venous blood within the venous vascular tree. All these are important risk factors for the formation of Flight Related DVT ²⁸.

Table 1

People at greater risk of developing a DVT

Diagnosis of Deep Vein Thrombosis and Pulmonary Thromboembolism

The diagnosis of DVT is sometimes difficult and failure to exclude a DVT can cause significant morbidity and mortality. Fortunately, clinical probability models with the aid of D-dimers and imaging techniques such as duplex scanning, provide promising diagnostic algorithms for both DVT and PE ^29,30,31,32. D-dimer levels is a blood test that provides information on the presence of fibrin formation or dissolution that occurs with ongoing thrombosis. However, as they can be elevated in conditions such as cancer, surgery or infectious disease, this is not a specific test for DVTs. The diagnostic usefulness of measuring plasma D-dimers was looked at in 117 patients hospitalized for with suspicion of a DVT or PE. Only 50% of positive D-dimers had a proven DVT or PE by pulmonary angiography or venogram ³³. What is relevant in clinical practice is the question whether the absence of D-dimers excludes the presence of a venous thrombosis. Research has failed to demonstrate that this is the case and that as there is a false negative value for this test, it cannot be used solely for DVT diagnosis ^34,35.  Traditionally a venogram has been the gold standard for DVT investigations.  However this has been superceded by non-invasive techniques such as the duplex scan which combines real-time ultrasound scanning with Doppler to illustrate the presence of thrombus within the venous system.  Doppler uses sound waves, which has its frequency shifted by the Doppler Shift principle, and allows the determination of the rate of blood flow. With the absence of venous blood flow or the inability to compress the venous system on the Duplex machine, the diagnosis of DVT is highly likely. In the presence of a good clinical history and a positive D-dimer, investigations must be performed to exclude a DVT. In the presence of a negative duplex scan but with a positive D-dimer, the duplex scan must be repeated. However, if both the D-dimers and duplex prove negative, a DVT can be safely excluded ³⁰.

Patients who present with a symptomatic PE (clinical signs of breathlessness with possible haemoptysis) will normally have a chest x-ray as a first line investigation. The signs within the chest x-ray, however, may be minimal. Signs of consolidation or the presence of pruning of the arterial vasculature may sometimes be evident.  A radionucleotide ventilation perfusion scan (VQ scan) can be used for the diagnosis of pulmonary emboli and this is quantified by the presence of a ventilation to perfusion defect. However, in many cases, the VQ scan can be difficult to interpret especially with the presence of other lung pathology. The present gold standard is the use of spiral CT angiography ³⁶. In addition, a patient with a high likelihood of a PE and who is shocked will need an immediate investigation and in these cases a spiral CT is the ideal radiological test³⁷.

Prophylaxis of Deep Vein Thrombosis    

Treatment and prophylaxis for DVT formation is controversial.  Drug treatments such as Aspirin are widely used as it has been shown to be effective for DVT prevention ³⁸.  The PEP trial (pulmonary embolism prevention) looked at 13,000 hip fracture patients of which there were a third less incidence of PE and DVT in those on Aspirin treatment ³⁹.  However there are risks involved with taking this drug, which includes peptic ulcer disease. The ideal dose of Aspirin for DVT prophylaxis is not exactly known but the PEP trial did show 160mg to be very effective.  As mentioned previously, due to the fact that the venous clot is mainly composed of red blood cells rather than platelets, then altering the coagulation cascade may prove to be a more effective method of prophylaxis than using Aspirin alone. 

There are 2 main groups of Heparin in common use today; the low molecular weight heparins, such as Tinzaparin and the unfractionated heparins, such as Calciparin.  The differences between the two are numerous.  Low molecular weight Heparin (LMWH) has a much lower molecular weight (on average 5,000 Daltons compared with the 15,000 molecular weight of unfractionated Heparin).  LMWH does have an action on antithrombin III (a coagulation factor) but due to its smaller weight, it has a longer half-life and a more predictable dose as there is less interaction with other serum proteins.  LMWH mainly inactivates factor Xa of the coagulation cascade and therefore is far superior compared to unfractionated Heparin.  There are also lower bleeding risks, there is a lower risk of Heparin-induced thrombocytopaenia and finally there is a reduced incidence of new thrombotic episodes ⁴⁰. LMWH is given as a once daily dose and there is no need for regular blood level monitoring. Recent evidence from the USA suggests that there is a higher risk of developing a spinal haematoma following a spinal anaesthetic and therefore its application in surgery has been limited ⁴¹.

Mechanical means of DVT prophylaxis must also be taken into account.  TED stockings help by reducing the cross-sectional area within the calf muscles.  By doing so, there is an improvement of venous flow and an increased emptying of pockets of stasis near to valve cusps.  Pressure is greater at the dorsal venous plexus and is gradually decreased as one moves up the leg.  There is strong evidence for the effectiveness of TED stockings.  Analysis of fifteen randomised trials showed that stockings decreased the risk of DVT by 64% in patients undergoing general surgical procedures ⁴².  It has also been shown that knee length stockings to be just as effective as above knee stockings.  Based on the experience that we have, stockings should be used 2 hours prior to their operation and continued until the patient is mobile. Similarly for passengers undergoing an airplane journey the stockings must be applied prior to boarding, and used until they are fully mobile.  The effects of above knee stockings are compromised when the knee is flexed in the 'sitting position'.   There are unfortunately complications with the use of stockings.  They impair the oxygenation of tissues and a 10mmHg of pressure leads to a 10% reduction of blood flow.  As a result, care must be taken when prescribing these stockings for patients with peripheral arterial disease and those patients with diabetes as they are at greatest risk.  The prescription of stockings are contra-indicated in those with an ankle brachial pressure index of less than 0.7 and we must stress that diabetic patients may have a falsely high reading due to the calcification of their blood vessel wall.  Compared with other agents, TED stockings with the use of LMWH is much better than either stockings or Heparin alone.

What advice should be given to the traveller?

As the result of public outcry surrounding the Economy Class Syndrome, the Government set up a House of Lords select committee in late 2000 ⁴³.  The press was critised for exaggerating the risks associated with the Economy Class syndrome.  They also stated that the term Economy Class Syndrome should not be used but instead, Flight Related DVT or Traveller’s Thrombosis would be more appropriate.  Finally it was suggested that airlines should provide a package of advice and provide accommodation for patients above the average size.  As you can see from Table 2, the advice for air travellers of low risk should mobilize as much as possible and exercise their calf muscles whilst seated.  They are also told to avoid excess alcohol and caffeine and to observe and act on advice given in in-flight media.  Those at moderate risk, such as those on the oral contraceptive pill, should perhaps take a low dose Aspirin and consider TED stockings.  The advice for high-risk air travellers included postponing their flight or they were advised to take LMWH. Prevention, although ideal, can be expensive for the individual passenger as illustrated in Table 3.  Unfortunately, patients who are at greatest risk of developing a Flight Related DVT are prevented from occupying the emergency exits, which provide the greatest amount of leg room, due to the risk imposed by the individual due to their size or immobility.

Table 2

Advice for Low Risk Passengers to help Prevent DVT

Table 3

Costs for DVT Prevention

Conclusion

The term Economy Class Syndrome should be replaced with either Flight Related Deep Vein Thrombosis or Traveller-Related Deep Vein Thrombosis. It can occur in any traveller irrespective of class of travel. There is an association between air travel and deep vein thrombosis but there is currently no epidemiological evidence to support air travel as causation of deep vein thrombosis. The risk is thought to be related to lack of exercise and immobility during long haul flights (greater than four hours). All passengers should be encouraged to mobilize during the flight and avoid excessive alcohol and caffeine intake and to keep well hydrated. All air flight carriers will have in flight leaflets giving further information as to what is available in-flight to combat deep vein thrombosis. The high risk and moderate risk travellers should seek medical advice before travel. Currently the Department of Health, Department of Transport, Local Government and the Regions have set up the Aviation Health Working Party who will oversee the research into Travel-Related Deep Vein Thrombosis and provide advice to air travellers and the airline industry.

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