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John Homans, M.D.,- THROMBOSIS OF THE DEEP LEG VEINS DUE TO PROLONGED SITTING, The New England Journal of Medicine, January 28, 1954.

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“SPONTANEOUS” thrombosis, according to DeCamp, Landry, Ochsner and DeBakey1, represents between 4 and 5 per cent of all venous thrombosis in limbs (the lower limbs almost exclusively). The very word indicates that the conditions under which the disease occurs in ambulatory persons have not been recognized. How sudden muscular efforts and strains may cause thrombosis in the deep lower-leg veins of even young and active men has been pointed out by Crane,s but such an influence is as often absent as present. Perhaps Naide’s3 accounts of thrombosis in tall men gives a better hint of the nature of the exciting factor. It suggests that prolonged dependency stasis, a state imposed by airplane flights, automobile trips and even attendance at the theatre, is able, unpredictably, to bring on thrombosis of this sort. During the London “blitz” pulmonary embolism often followed immediately on long periods of sitting in air-raid shelters, as described by Simpson.4 His account reveals the nature of the insecure propagating process in the deep veins of the calf, notably in how few hours of sitting still a fatal thromboembolism may be set up. As a preventive, he pleads for bunks in the shelters. The cases described below indicate the importance of recognizing the prolonged sitting position as the occasion of a not too rare disease.

Case1, An active 54-year-old physician flew from Boston to Venezuela on July 4, 1946. The flying time was about 14 hours, in hops of 6 or 7 hours. In Caracas he was much on his feet, and he returned on July 7. On this flight he took short naps, but his calves did not rest upon a support, though he crossed his knees at times. On reaching home, an hour or 2 after leaving the plane, he noticed lameness in his right calf, but hobbled about on that day (July 8). On July 9, examination revealed slight deep tenderness over the posterior tibial vessels, rather high in the calf, and definite painful resistance to dorsiflexion of the foot. There was no edema, cyanosis or skin infection (such as might cause popliteal adenitis). A diagnosis of deep phlebothrombosis was made The prothrombin was found to be 100 per cent. Having easy access to a blood laboratory and with active teaching to do, the patient desired to remain ambulatory. A semi-elastic bandage was worn from toes to knee, to maintain as far as possible an even venous compression, and he was given 300 mg. of Dicumarol. During the 2 succeeding days, smaller doses followed, and on July 12, the 3d morning after the disease had been noticed and treatment started, pain and lameness, already lessened on the previous day, were found to be absent. The prothtombin was 15 per cent, and there was slight oozing of blood from the nose. From this time on, no medication was used. Complete recovery followed and has since been maintained.

Immediately after a long airplane flight, a well localized venous thrombosis, in one of the major vascular systems of the upper calf, accompanied by a mild inflammatory reaction, was favorably influenced by Dicumarol and gave no further signs as soon as the prothrombin fell to 15 per cent. Evidently a very early process was checked and healed before it had time to spread. The rapid disappearance of pain and lameness was remarkable, but since the treatment of such an early, acute disease, without bed rest, is so rare an event, it is impossible to say whether or not it should have been expected.

Peter H Beighton and Peter R Richards, Hillingdon Hospital – CARDIOVASCULAR DISEASE IN AIR TRAVELLERS, Brit Heart J., 1968, 30, 367

There has been a great increase in civil aviation in the post-war years. In 1966, more than a million passengers a month passed through London Airport. Flying has become so safe and convenient that many disabled people elect to travel by this means. In fact, as many as 5 per cent of passengers on routine scheduled services are suffering from some form of disability, though less than 1 per cent are self-declared invalids.

In the modern jet airliner, the passengers are exposed to a mild degree of hypoxia at ordinary cruising altitudes, due to the reduction in cabin atmospheric pressure. This degree of hypoxia is insufficient to affect healthy adults, but may prove an embarrassment to passengers with impairment of the cardiovascular or respiratory systems. This group accounts for up to 20 per cent of self-declared invalids.

This paper analyses some 25 patients who were admitted to Hillingdon Hospital, a large general hospital near London Airport, during the years 1963, 1964 and 1965. All had collapsed with conditions affecting their cardiovascular systems, either during or immediately after a normal routine flight. The pertinent physiological and environmental factors are discussed, and the routine procedure for handling invalid passengers is described.

Ian S Symington and Bryan H R Stack – PULMONARY THROMBOEMBOLISM AFTER TRAVEL, Br J Dis Chest (1977) 71, 138
Summary: Pulmonary thromboembolism developed in eight parties shortly after travel. Pre-existing vein disease was present in this group. Possible prophylactic measures are suggested.
Introduction: Venous stasis predisposes to intravascular deep vein thrombosis (Virchow 1856). It would be expected that travellers who sit for long periods in motor vehicles, trains or aircraft would be prone to develop deep vein thrombosis and its thromboembolic sequelae. There have been few reports, however, of this occurrence. Beighton and Richards (1968) describe one death from paradoxical embolism after air travel and Horsley et al. (1975) reported seven cases of deep venous thrombosis and pulmonary thromboembolism in a series of 186 medical emergencies among holidaymakers in Cornwall, many of whom had presumably travelled there by car. We wish to describe eight cases of pulmonary thromboembolism which occurred after travel.

J.A. Ledermann, Ali Keshavarzian, Hillingdon Hospital – ACUTE PULMONARY EMBOLISM FOLLOWING AIR TRAVEL – Postgraduate Medical Journal (February 1983) 59, 104-105

Three cases of pulmonary embolism following long air flight are described. There was no previous history of venous disease. The symptoms were transient in one and severe in two. The occurrence of pulmonary embolism immediately after air travel is emphasized.

R Sarvesvaran MBBS (Ceylon), DMJ (Clin et Path) – SUDDEN NATURAL DEATHS ASSOCIATED WITH COMMERCIAL AIR TRAVEL, Med Sci. Law (1986) Vol. 26, No. 1

A study of the causes of sudden natural deaths associated with commercial air travel, during the period February 1979 to January 1982 at the world’s busiest international airport (Heathrow, London) was undertaken. Amongst long-distance passengers, fatal pulmonary embolism caused 18 per cent of deaths, 81.8 per cent occurring amongst females.

M Marshall and J A Dormandy – OEDEMA OF LONG DISTANT FLIGHTS, Phlebology (1987) 2, 123-124

Introduction: Swelling of the legs is not necessarily a symptom of disease, but can be a consequence3 of the fact that man was not meant to sit immobile for 14 hours. It can be found in persons with healthy veins, if they are subject to an extreme orthostatic load. Such loads may be of various types, but certainly include sitting cramped in a condition of almost complete immobility, as is customary nowadays in international flights. Flights lasting more than 2 to 3 hours often lead to oedema of the legs. The object of this randomised double blind controlled study, on the occasion of a 15 hour flight of a number of European phlebologists to the 9th World Congress for Phlebology in Kyoto, was to document the extent of the oedema and the degree to which it can be prevented by drugs.
Methods: The maximum circumference of the foot around the heel (H-size) and the smallest circumference around the ankle (B-size) were measured in 19 participants half an hour after the departure of the aircraft and 3 hours and 14 hours later. None of the subjects had past history of venous disease or chronic leg oedema. All the measurements were carried by the same investigator (M.M) and each set of measurements took one and a half hours. Subjects were measured in the same sequence each time. Only the usual amount of movement was allowed. A horse-chestnut seed extract (Venostasin retard) or placebo medication was started 10 days prior to the beginning of the flight and was continued twice daily until the landing in Tokyo. (Each 300mg capsule of horse-chestnut seed extract is standardised to contain 50 mg of triperpene glycosides; manufactured by Klinge Pharma Munchen 80).
Results: Ten participants in the study received Venostasin retard, nine received the placebo. The mean (and standardisation deviation) of B-size in the treated and control groups at the beginning of the flight were 22.5 (1.1) cm and 22.1 (1.4) cm respectively.

H. Landgraf, M.D., Ph.D., B. Vanselow, M.D., Ph.D., D. Schulte-Huermann, M.D., Ph.D., M.V. Mülmann, M.D., Ph.D., L. Bergau, M.D., Ph.D. – ECONOMY CLASS SYNDROME: RHEOLOGY, FLUID BALANCE, AND LOWER LEG EDEMA DURING A SIMULATED 12-HOUR LONG DISTANCE FLIGHT – Aviation, Space and Environmental Medicine – October 1994

In order to study pathological chances that might lead to deep vein thrombosis and pulmonary embolism in long-distance air travel passengers, 12 healthy volunteers were investigated during 4 simulated 12-h flights (day and night). The influence of repeated leg exercise was compared with constant sitting. Plasma viscosity, hematocrit, albumin, fluid balance, and lower leg swelling were measured. Rheological studies showed only circadian rhythm alterations. An average of 1150 ml fluid was retained, which correlated with an increase in body weight. The lower leg volume increase was significant, but not pathological. Periodic leg exercising showed no measurable preventive effects. These changes in healthy human volunteers are within physiological variations and are not sufficient to provide a definitive cause of venous thrombosis in healthy passengers. They do, however, suggest alternations produced by long-distance air travel that could intensify the risk of developing deep venous thrombosis in passengers with predisposing risk factors.

Bettina Pfausler, Hann Vollert, Silvia Bosch, and Erich Schmutzhard – CEREBRAL VENOUS THROMBOSIS – A NEW DIAGNOSIS IN TRAVEL – J Travel Med 1996; 3:165-167
Cerebral venous thrombosis is a syndrome seen in association with a large number of disease processes. The commonest reported causes in adults are oral contraception, pregnancy and complications associated with the postpartum period, systemic malignancy and infection. In approximately 20% of adult cases reported during the past 20 years no etiology was established. Cerebral venous thrombosis can be caused by similar mechanisms, such as venous thrombosis, occurring elsewhere in the body, e.g. blood vessel wall alterations attributable to inflammation, infection, or invasion of malignant cells, as well as from changes in blood flow due to dehydration and changes in the coagulability of the blood (e.g., from use of oral contraceptive). PC Gates and JHM Barnett list 38 causes of cerebral venous thrombosis that were proven by angiography or autopsy. One item on their list was dehydration/hyperpyrexia. Recently thrombosis of the venae saphena or femoralis/iliaca has been reported to occur in long distance air travellers. We would like to report on five (out of 15) in whom cerebral venous thrombosis was causatively linked with either long distance air travel alone, air travel and diarrhea, or air travel and exposure to tropical heat.

Bo Eklof, MD, Robert L. Kistner, MD, Elna M. Masuda, MD, Bryan V. Sonntag, MD, Howard P. Wong, MD – VENOUS THROMBOEMBOLISM IN ASSOCIATION WITH PROLONGED AIR TRAVEL, 1996 BY THE American Society for Dermatologic Surgery.

Objective: To study risk factors for the development of air travel-related acute venous thromboembolism. Methods. 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 patients who developed symptoms during or after air flight. Results. There were 24 males and 20 females with a mean age of 63 years. Flight times were 5-17 hours. Twenty-eight patients (63.6%) had DVT only, five patients (11.4%) PE only, and 11 patients (25%) DVT and PE. Ninety-five percent had extension of the thrombus above the calf: popliteal vein, 10 patients; superficial femoral vein, 13 patients; common femoral vein, six patients; and iliac vein, eight patients. Five patient-related risk factors were identified; history of previous DVT (34%), presence of chronic disease or malignancy (25%), hormone therapy (16%), recent lower limb injury (11%), and recent surgery or femoral catheterization (9%). Conclusions. We can speculate about the role of seven cabin-related risk factors; low humidity, hypoxia, diuretic effect of alcohol, insufficient fluid intake, smoking, “coach” position, and immobilization. In travellers with patient-related risk factors, the cabin-related risk factors are superimposed and may increase the risks for air travel-related acute venous thromboembolism. Active prophylaxis is recommended. Dermatol Surg 1996; 22:637-641.

Alicia Mercer, M.D., and Joel D. Brown, M.D., DTMH – VENOUS THROMBOEMBOLISM ASSOCIATED WITH AIR TRAVEL: A REPORT OF 33 PATIENTS, Aviation Space and Environmental Medicine, Vol. 69, No. 2 – February 1998

Background: The medical literature suggests long distance travel, particularly air travel, may be a risk factor for venous thromboembolism, but the risk is poorly quantified. Methods: We reviewed 134 records of patients hospitalized with venous thromboembolism for comments regarding recent travel. Patients who had traveled within 31 d prior to venous thromboembolism were defined as recent travellers. Results: Of 134 patients records, 66 (49%) had documented inquiries regarding travel and 33 (50%) were recent air travellers. Data regarding demographics, mode of travel, day of onset of symptoms in relation to travel, and other risk factors for venous thromboembolism were abstracted from the records of the recent travellers. There were 12 (36%) travellers who had no other predisposition for venous thromboembolism. All had traveled non-stop by aircraft for 4 or more hours; none was identified as crew-member. The median day of onset of venous thromboembolism was on travel day 4 (range: day 1-31). There were 8 (24%) patients who had onset during air travel or on the day of arrival, and 27 (82%) had onset by travel day 15. Air travel for 4 or more hours within the preceding 31 d was the most common risk factor for venous thromboembolism in our study patients and was present in 50%. This incidence is much higher than previously described, perhaps due to limiting the study population to those in which the presence or absence of travel was documented. Conclusion: Prospective studies are needed to better define the risk factors for venous thromboembolism among long distance air passengers and crew-members, and to determine effective preventive measures.

John M Cruickshank, Richard Gorlin, Bryan Jennett – AIR TRAVEL AND THROMBOTIC EPISDOES: THE ECONOMY CLASS SYNDROME. The Lancet, August 27, 1998
People on long air flights are at risk from deep vein thrombosis (DVT) and pulmonary emboli, even if relatively young and without a past history of cardiovascular disease. Stasis of the lower limbs, exacerbated by cramped conditions in economy class and dehydration due to excessive alcohol intake, are probably the main causes. Journeys as short as three to four hours may be potentially dangerous. The embolic event may be precipitated by movement, sometimes a week or two after the flight, and need not be preceded by a painful calf. Affluence, cheap travel package holidays, and international business activity ensure that long distance air travel has become common place. However, the hazards of such long trips, often under cramped conditions, are not appreciated by most travellers and the airline companies make no effort to enlighten them, Virchow first pointed out that venous stasis predisposed to deep vein thrombosis (DVT). The high incidence of DVT and pulmonary emboli during the second world war in civilians under cramped conditions in air-raid shelters was reduced only after the introduction of bunk-beds. Long car trips can be associated with pulmonary emboli, and similar problems may occur in long distance air travellers and can cause sudden death, even in the absence of a history of cardiovascular problems. The diagnosis is not always obvious, and pulmonary embolus can masquerade as soft tissue injury, pneumonia, bacterial endocarditis, gastrointestinal disease, and cerebrovascular disease. We describe six cases to emphasizes the hazards of long distance air travel, and discuss prophylactic measures necessary to reduce risk. Three had a possible predisposing cause for thromboembolism, and their details are summarized in the table. The others had no predisposing medical history.

D. Loew, H.E. Gerlach, K.H. Altenkämper and B. Schneider – EFFECT OF LONG-DISTANCE FLIGHTS ON OEDEMA OF THE LOWER EXTREMITIES – Phlebology (1998) 13:64-67. 1998 The Venous Forum of the Royal Society of Medicine and Societas Phlebologica Scandinavica.

Objective: During long-distance flights, passengers complain of leg heaviness and oedema in the feet, ankles and distal parts of the lower extremities. Among the rarer complications are thrombophlebitis, thrombosis and pulmonary embolism. The aim of this study was to compare the efficacy of class II elastic stockings with no stockings and a venoactive compound (dried extract of vine leaves) and with a diuretic combination for preventing venous oedema during a long-distance flight. Design: Open, randomized study on outward-bound and return flights, volunteers having been administered the venoactive compound Antistax (n=13) or no medication (n = 13); nine subjects received the fixed diuretic combination only on the outward-bound flight. Each subject (n = 35) wore a class II compression stocking (Sigvaris 902/A-D) on one leg. Main outcome measures: Water displacement volume measurements of the lower limb; secondary end-points; clinical oedema, subjective symptoms, phlebological status, clinical and Doppler findings. Results: The most effective measure in preventing lower limb oedema was the individually fitted elastic support stockings. The venoactive drug Antistax was ineffective. The diuretic combination did have an effect in combination with the compression stocking. Conclusion: During long-distance flights, compression stockings are more effective in preventing oedema in the lower limbs than the venoactive dried extract of vine leaves. The diuretic combination had a marked effect in combination with compression.

Emile Ferrari, MD; Thierry Chevallier, MD; Alexis Chapelier, MD; and Marcel Baudouy, MD – TRAVEL AS A RISK FACTOR FOR VENOUS THROMBOEMBOLIC DISEASE – A CASE-CONTROL STUDY – February 1999
Background: The link between travel and the risk of venous thromboembolic disease (VTED) has been widely suspected. However, only cases or series of cases have been reported in the literature. Study objectives: By means of a case-control study, we sought to confirm this relationship and to determine the main features, if any, of these post-travel VTEDs. Design: The history, in particular the history of recent travel, of 160 patients presenting in our department with VTED was scrupulously investigated. All journeys undertaken during the preceding 4 weeks and lasting > 4 h by whatever means of transport were considered. The same questionnaire was submitted to a control group. Results: When the two groups of patients are compared, a history of recent travel is found almost four times more frequently in the VTED group (p < 0.0001). The odds ratio for having a VTED in patients who travelled was 3.98 (95% confidence interval, 1.9 to 8.4). Means of travel used included the train in 2 cases, airplane in 9, and car in 28. Mean duration of travel was 5.4 = 2.1 h. These post-travel VTEDs are not confined to a specific location, seem to involve no particular predisposition, and are more often “idiopathic.” This fact supports the hypothesis that travel alone can produce vein clot formation. Conclusions: A history of recent travel is a risk factor for VTED. Post-travel venous thrombotic events can occur after short journeys in patients with no other risk factors or concomitant disease.

Patrick Kesteven, MB BS FRCP FRACP FRCPath PhD Consultant Haematologist, Brian Robinson BSc(Hons) FIBMS DMLM CertEd RGN Haematology Research Nurse, Freeman Hospital – AIR TRAVEL AND VENOUS THROMBOSIS
Reports of an association between commercial air travel and venous thromboembolic disease (VTE) have been appearing for over 40 years. Media attention became focused when the term ‘economy class syndrome’ was coined in 1988. This term may be misleading as there is no evidence (for or against) to suggest that VTE occurs more commonly in economy class. Indeed, there have been some well-publicised cases recently of pulmonary embolism following flights in first class. The term ‘travellers thrombosis’ may be more appropriate. Immobility as a causative factor in VTE has been recognised for many decades, Shortly after the start of heavy bombing of London in 1940, Simpson noted a six-fold increase in the incidence of fatal pulmonary embolism, occurring in, or more frequently just after leaving, air raid shelters. The author was in no doubt that the cause was spending long periods (up to ten hours) in deck chairs, compressing calf veins, precipitating VTE which then embolised on movement. He also observed a fall in the incidence of this problem coinciding with the introduction of bunks to the shelters. The literature on VTE and flying consists predominantly of case reports, anecdotes and hypotheses. Given the infrequency of this complication, the likelihood that many cases remain undiagnosed and the difficulties in carrying out prospective studies, the paucity of reports is unsurprising. An early report of medical complications of commercial flights appeared in 1968, detailing the 42 admissions to Hillingdon Hospital, over a three-year period, of passengers arriving at Heathrow acutely ill. Although only one of these cases had VTE, much of the paper was concerned with changes in oxygen tension, alveolar partial pressures and temperature at high altitude. This may have coloured subsequent thinking on the subject. However, several large series have been published recently that examine travel as an aetiological factor in all patients with VTE admitted to hospital. The first study found 25.9% of 3,307 consecutive DVT cases had travelled recently. Two studies from Honolulu uncovered travel as a factor in 33 of 154 VTE cases, and 44 of 254 cases – all related to flying. Importantly, both studies demonstrated that the majority of such patients had other risk factors for VTE. A study from Nantes reported a similar proportion due to travel (39 of 160), although only nine were related to flying, while 28 followed a trip by car and two by train. All studies suggest that seated immobility is the main precipitating factor in travellers’ thrombosis, probably through creasing of the popliteal veins. Several of these studies have made the observation that underlying thrombotic risks are often present, such as previous or family history of VTE, hormone treatment and malignancy. Although it would be expected that the longer the immobility the greater the risk, it is interesting that even short periods (three to four hours) have been reported to precipitate VTE. Most cases develop symptoms with 96 hours of the trip, although some can present up to four weeks later (often taken as the arbitrary cut-off period in most studies). Some have suggested dehydration as a factor, for which there is conflicting evidence. Other postulated in-flight risk factors have included hypoxia, alcohol, hand luggage placement, smoking, and changes in temperature, seasons, sleep patterns, hormonal levels and time zones. There is little evidence to support these theories and some that appears to refute them.

Paul L F Giangrande – THROMBOSIS AND AIR TRAVEL, J Travel Med 2000; 7: 149-154
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 impairment of venous circulation due to prolonged immobility in a cramped position, in the pathogenesis of the thrombosis. A number of risk factors specific to air travel are recognised, including immobility (leading to stasis in the lower limbs and haemoconcentration), compression of the popliteal vein by the edge of the seat, and dehydration. However, inherited haematological abnormalities may also predispose to thrombosis. This article reviews the pathophysiology of venous thrombosis, and gives advice on prevention as well as guidelines on the management of established thromboembolism.

Pulmonary Embolism Prevention (PEP) Trial Collaborative Group - PREVENTION OF PULMONARY EMBOLISM AND DEEP VEIN THROMBOSIS WITH LOW DOSE ASPIRIN: PULMONARY EMBOLISM PREVENTION (PEP) TRIAL. Reprinted from The Lancet, Vol. 355, No 9212, Pages 1295-1302, 15 April 2000

Previous trials of antiplatelet therapy for the prevention of venous thromboembolism have individually been inconclusive, but a meta-analysis of their results indicated reductions in the risks of deep-vein thrombosis and of pulmonary embolism in various high-risk groups. The aim of this large randomized placebo-controlled trial was to confirm or refute these apparent benefits.

BjØrn Bendz, Morten, Morten Rostrup, Knut Sevre, Trine O Andersen, Per Morten Sandset. ASSOCIATION BETWEEN ACUTE HYPOBARIC AND ACTIVATION OF COAGULATION IN HUMAN BEINGS, The Lancet, Vol 356, November 11, 2000

The risk of venous thrombosis is thought to be increased by flying. In a study of 20 healthy male volunteers who were suddenly exposed to a hypobaric environment similar to that encountered within aeroplane cabins, markers of activated coagulation transiently increased by two-fold to eight-fold. We suggest that hypobaric hypoxia, with sedentariness and dehydration, may cause this increased risk of venous thrombosis.

John H Scurr, Samuel J Machin, Sarah Bailey-King, Ian J Mackie, Sally McDonald, Philip D Coleridge Smith – FREQUENCY AND PREVENTION OF SYMPTOMLESS DEEP-VEIN THROMBOSIS IN LONG-HAUL FLIGHTS: A RANDOMISED TRIAL – The Lancet, Vol 357, May 12, 2001

Background. The true frequency of deep-vein thrombosis (DVT) during long-haul air travel is unknown. We sought to determine the frequency of DVT in the lower limb during long-haul economy-class air travel and the efficacy of graduated elastic compression stockings in its prevention. Methods. We recruited 89 male and 142 female passengers over 50 years of age with no history of thromboembolic problems. Passengers were randomly allocated to one of two groups: One group wore class-1 below-knee graduated elastic compression stockings, the other group did not. All the passengers made journeys lasting more than 8 h per flight (median total duration 24 h), returning to the UK within 6 weeks. Duplex ultrasonogrpahy was used to assess the deep veins before and after travel. Blood samples were analysed for two specific common gene mutations, factor V Leiden (FVL) and prothrombin G20210A (PGM), which predispose to venous thromboembolism. A sensitive D-dimer assay was used to screen for the development of recent thrombosis. Findings. 12/116 passengers (10%; 95% CI 4.8-16.0%) developed symptomless DVT in the calf (five men, seven women). None of these passengers wore elastic compression stockings, and two were heterozygous for FVL. Four further patients who wore elastic compression 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-1 compression stockings developed DVT (95% Ci 0-3.2%). Interpretation. We conclude that symptomless DVT might occur in up to 10% of long-haul airline travellers. Wearing of elastic compression stockings during long-haul air travel is associated with a reduction in symptomless DVT.

Frédéric Lapostolle, M.D., Vanessa Surget, M.D., Stephen W. Borron, M.D., Michel Desmaizieres, M.D., Didier Sordelet, M.D., Claude Lapandry, M.D., Michel Cupa, M.D., and Frédéric Adnet, M.D., PH.D. SEVERE PULMONARY EMBOLISM ASSOCIATED WITH AIR TRAVEL. New England Journal of Medicine, Vol 345, No. 11, September 13, 2001

Background - Air travel is believed to be a risk factor for pulmonary embolism, but the relation between pulmonary embolism and distance flown has not been documented. The aim of this study was to investigate whether the duration of air travel is related to the risk of pulmonary embolism.
Methods – From November 1993 to December 2000, we systematically reviewed all cases of pulmonary embolism requiring medical care on arrival at France’s busiest international airport. Data on the geographic origins of all flights and the numbers of passengers were collected in order to evaluate the incidence of pulmonary embolism per million passenger arrivals as a function of the distance traveled.
Results – A total of 135.29 million passengers from 145 countries or other areas arrived at Charles de Gaulle Airport during the period of the study, of whom 56 had confirmed pulmonary embolism. The incidence of pulmonary embolism was much higher among passengers travelling more than 5000 km (3100 mi) (1.5 cases per million, as compared with 0.01 case per million among those travelling less than 5000 km). The incidence of pulmonary embolism was 4.8 cases per million for those travelling more than 10,000 km (6200 mi).
Conclusions – A greater distance traveled is a significant contributing risk factor for pulmonary embolism associated with air travel. (N Engl J Med 2001; 345:779-83.)

Fabrice Boulay, Frédéric Berthier, Grégory Schoukroun, Charles Raybaut, Yves Gendreike, Bruno Blaive – SEASONAL VARIATIONS IN HOSPITAL ADMISSION FOR DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM: ANALYSIS OF DISCHARGE DATA, BMJ Volume 323, 15 September 2001.
Seasonal variation in fatal pulmonary embolism has been well documented by at least 23 reports comprising nearly 11 000 cases. Evidence is lacking, however, for seasonal variation in deep vein thrombosis – the only large hospital series available did not establish significant variation. We analysed hospital admissions for deep vein thrombosis and pulmonary embolism in France over four years.
Methods and Results. We reviewed all cases with a discharge diagnosis of deep vein thrombosis or pulmonary embolism entered on the national hospital discharge register between 1995 and 1998. We used the international classification of disease, ninth and 10th revisions (Deep vein thrombosis: ICD-9 codes 451.1 and 451.2 and ICD-10 codes 180.1 and 180.2; pulmonary embolism: ICD-9 code 415.1 and ICD-10 codes 126.0 and 126.9). This dataset is a collection of all discharges from public and non-profit making, short stay, or acute hospitals in France (71% of hospital capacity). We included discharge data if the usual confirmatory tests – or specific fibrinolytic or surgical therapy - were mentioned, Usually confirmatory tests were venography or Doppler ultrasonography for deep vein thrombosis and a ventilation and perfusion lung scan, helicoidal computed tomography, or pulmonary angiography for pulmonary embolism. The figure shows monthly data on admission to hospital for deep vein thrombosis (n = 65 081, median age 69 years =, 58% women, 95% medical patients) and pulmonary embolism (n = 62 237, median age 68 years, 57% women, 96% medical patients), presented as percentages above or below the average monthly value for each year of the study, the sum of monthly variations being 0. The number of admissions per month was significantly higher in winter and lower in summer for both deep vein thrombosis and pulmonary embolism (Roger’s test: P <0.0001). Mean monthly admissions for deep vein thrombosis (1356 (SD 450)) ranged from 18% below average in August 1996 to 18% above average in February 1996 and December 1997. Mean monthly admissions for pulmonary embolism (1297 (SD 268)) ranged from 22% below average in August 1998 to 26% above average in December 1997. The same winter predominance was observed for cases of deep vein thrombosis without confirmatory tests (n= 34 245); cases of deep vein thrombosis without pulmonary embolism (n = 47 508); and sub-groups of deep vein thrombosis and pulmonary embolism defined by age, sex and surgical setting (data not shown).

D F H Pheby and B W Codling – PULMONARY EMBOLISM AT AUTOPSY IN A NORMAL POPULATION: IMPLICATIONS FOR AIR TRAVEL FATALITIES – Aviation, Space and Environmental Medicine, Vol. 00, No. 0 Month 2002

Background: Much attention has been focused on the apparent risk to long-haul air travellers of venous thromboembolism (deep vein thrombosis (DVT) and pulmonary embolism (PE)), following a number of well-publicized cases. However, there is little epidemiological data to elucidate the problem. PE tends to be under-diagnosed as a cause of death in the general population. This study sets out to establish the level of risk of fatal PE among long-haul passengers arriving in the UK, on the basis of a reappraisal of the role of PE in mortality in the general population. Methods. Autopsies carried out at Gloucester in 1996-2000 were reviewed to determine age-specific morality rates for PE for West Gloucestershire. These rates were applied to long-haul air travellers arriving in the UK, for whom the number of passenger-years at risk were calculated, to estimate the expected numbers of deaths in this group. Results: In 3764 autopsies, PE was the primary cause of death in 221 cases (5.9%), while in 304 (8.1%) it was present as an incidental finding. This suggests that PE was involved in approximately 13.9% of deaths, and are more common with age. Passenger years at risk per annum among long-haul passengers arriving in the UK were estimated (mid-range) at 21,830.482; it was anticipated that 6.55 deaths involving PEs, but not related to air travel, could be expected annually in this group. Conclusions. It appears that the risks of venous thromboembolism due to air travel are overstated. Some deaths are bound to occur in-flight, but there is no evidence to suggest an increase, though clearly there are predisposing risk factors for DVT present on long journeys.

Maria Rosaria Cesarone, MD, Gianni Belcaro, MD, PhD, Andrew N. Nicolaides, MD, MS, Lucrezia Incandela, MD, Maria Teresa De Sanctis, MD, George Geroulakos, PhD, Andrew Lennox, PhD, Kenneth A. Myers, MS, M. Moia, MD, Edmondo Ippolito, MD, and Michelle Winford, Pescara, Italy; London; and Melbourne, Australia VENOUS THROMBOSIS FROM AIR TRAVEL: THE LONFLIT3 STUDY – PREVENTION WITH ASPIRIN VS LOW-MOLECULAR-WEIGHT HEPARIN (LMWH) IN HIGH-RISK SUBJECTS: A RANDOMIZED TRIAL, Angiology, Volume 53, Number 1, 2002

The LONFLIT1 and 2 studies established that in high-risk subjects after long (>10 hours) flights, the incidence of deep venous thrombosis (DVT) may be between 4% and 6%. The LONFLIT3 study aimed to evaluate methods of prevention in high-risk subjects. Of 467 subjects contacted for the study, 300 were included. These 300 subjects at high risk for DVT were randomized, after informed consent, into three groups: 1) a control group that had no prophylaxis; 2) an aspirin treatment group, in which parties were treated with 400 mg (tablets of oral , soluble aspirin; one dose daily for 3 days, starting 12 hours before the dose of enoxaparine was injected between 2 and 4 hours before the flight. The dose was weight-adjusted (100 IU (equivalent to 0.1mL) per 10 kg of body weight). Subjects with potential problems due to prophylaxis with aspirin or LMWH or at risk of drug interactions were excluded. Of the 100 included subjects in each group, a total of 249 subjects completed the study (dropouts due to low compliance or travelling/connections problems were 17%). Age and sex distribution were comparable in the three groups as well as risk distributions. Mean age was 47 (range, 28-75; SD, 11; 65% males). Of the 82 subjects in the control group, there were 4.82% of subjects with DVT with two superficial thromboses. In total 4.8% of limbs suffered a thrombotic event. Of 84 subjects in the aspirin treatment group, there were 3.6% of patients with DVT and three superficial thrombosis. In total 3.6% of limbs had a thrombotic event. In the LMWH group (82 subjects), there were no cases of DVT. One superficial thrombosis was documented. In total only 0.6% of limbs had a thrombotic event (p<0.002 in comparison with the other two groups.) DVT was asymptomatic in 60% of subjects; 85% of DVTs were observed in passengers in non-aisle seats. Mild gastrointestinal symptoms were reported in 13% of patients taking aspirin. One dose of LMWH is an important option to consider in high-risk subjects during long-haul flights.

Gianni Belcaro, MD, PhD, Maria Rosaria Cesarone, MD, Sandeep S.G. Shah, MD, Andrew N, Nicolaides, MS, MD, George Geroulakos, PhD, Edmondo Ippolito, MD, Michelle Winford, Andrew Lennox, PhD, Luciano Pellegrini, MD, Rosella Brandolini, MD, Kenneth A. Myers, MS, Emilio Simeone, MD, Peter Bavera, MD, Mark Dugall, MD, Andrea Di Renzo, and Marco Moia, MD, San Valentino Italy; London, UK; and Melbourne, Australia –PREVENTION OF EDEMA, FLIGHT MICROANGIOPATHY AND VENOUS THROMBOSIS IN LONG FLIGHTS WITH ELASTIC STOCKINGS. A RANDOMIZED TRIAL – THE LONFLIT 4 CONCORDE EDEMA – SSL STUDY
Angiology Volume 53, Number 6, 2002.

The LONFLIT1/2 studies have established that in high-risk subjects after long (>10 hours) flights the incidence of deep venous thrombosis (DVT) is between 4% and 6%. The LONFLIT4 study has been planned to evaluate the control of edema and DVT in low-medium-risk subjects. The aim of this study was to evaluate edema and its control with specific flight stockings, in long-haul flights. In the first part of the study 400 subjects at low-medium risk for DVT were contacted; 28 were excluded for several non-medical problems; 372 were randomized into 2 groups to evaluate prophylaxis with stockings in 7-8 hour flights; the control group had no prophylaxis. Below-knee, Scholl, Flight Socks, producing 14-17mm Hg of pressure at the ankle, were used in the treatment group. The occurrence of DVT was evaluated with high-resolution ultrasound scanning (femoral, popliteal, and tibial veins). Edema was assessed with a composite score based on parametric and nonparametric measurements. Part II: In this part of the study 285 subjects at low-medium risk for DVT were included and randomized into 2 groups to evaluate edema prophylaxis in 11-12-hour flights; the controls had no prophylaxis while the prevention group had below-knee, Scholl Flight Socks (comparable to part I). Results. Part I: DVT evaluation. Of the 184 included subjects in the stockings group and 188 in the control group, 358 (96.2%) completed the study. Dropouts were due to compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 179 subjects (mean age 49; SD 7; M:F = 101:78), none had DVT or superficial thromboses. Control Group: of 179 subjects (mean age 48,4; SD 7.3; M:F = 98.81), 4 (2.2%) had a DVT. There were also 2 superficial thromboses. In total, 3.35% (6) subjects had a thrombotic event. The difference (p<0.002) is significant. Intention –to-treat analysis detects 15 failures in the control group (9 lost + 6 thromboses) out of 188 subjects (7.9%) versus 56 subjects (2.7%) in the stockings group (p<0.05). All thrombotic events were observed in passengers sitting in non aisle seats. The tolerability of the stockings was very good and there were no complaints or side effects. Thrombotic events were asymptomatic. No difference was observed in the distribution of events between men and women. The 3 women who had a thrombotic event were taking low-dose, oral contraceptives. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 6.7 (3.1) in controls; in the stockings group the score was 2.9 times lower (p<0.05). The control of edema with stockings was clear considering both parametric (circumference, volume) and nonparametric (analogue scale line) data. Part II: DVT evaluation. Of the 285 included subjects, 271 (95%) completed the study. Dropouts were due to low compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 142 subjects (mean age 48; SD 8; M:F = 89:53), none had DVT or superficial thromboses. Control group: of 143 subjects (mean age 47; SD 8; M:F = 87:56), 3 had a popliteal DVT and 3 a superficial thrombosis. In total , 4.2% (6) SUBJECTS HAD A THORMBOTIC EVENT. The difference (p<0.02) between groups is significant. Intention-to-treat analysis detects 14 failures in the control group (8 lost + 6 thromboses = 9.7%) versus 6 (all lost = 4.2% in the stockings group) (p<0.05). Four of 6 events (3 DVT + 1 SVT) were observed in the distribution of events between men and women. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 8.08 (2.9) in controls while in the stockings group the score was 2.56 (1.5) (p<0.005). In conclusion. Scholl Flight Socks are very effective in controlling edema. Also this type of compression is effective in significantly reducing the incidence of DVT and thrombotic events in low-medium-risk subjects, in long-haul flights. Conclusions: Considering these observations, Flight Socks are effective in controlling edema and in reducing the incidence of DVT in low-medium-risk subjects, in long-haul flights (7-11 hours).

Wolfgang Schobersberger, Dietmar Fries, Markus Mittermayr, Petra Innerhofer, Guenther Sumann, Beatrix Schobersberger, Anton Klingler, Viktor Stöllnberger, Uwe Fischbach, Hanns Christian Gunga, - CHANGES OF BIOCHEMICAL MARKERS AND FUNCTIONAL TESTS FOR CLOT FORMATION DURING LONG-HAUL FLIGHTS, Thrombosis Research 108 (2003) 19-24

Introduction: Long-haul flights have been suggested to be associated with an increased risk for thromboembolic events. Until now, changes in the coagulation system during an actual flight have not been investigated. Materials and methods: To explore whether any changes occur in the coagulation system during an real long-haul flight molecular markers for coagulation and fibrinolysis were measured in 20 volunteers (10 subjects with a low and 10 with a moderate risk for venous thromboembolism (VTE)) during and after a return flight from Vienna to Washington. In addition, functional measurements of coagulation were performed using activated Thrombelastographic. Results: Thrombelastographic measurements revealed activation of coagulation in all passengers, who showed an increased activity of FVII and FVIII as well as suppressed fibrinolysis. There was no evidence of a pronounced thrombin and fibrin formation. We did not find any differences between both groups concerning coagulation changes. Conclusions: Long-haul flights induce a certain activation of the coagulation system. This activated coagulation could be a risk factor for VTE during long-haul flights mainly when other risk factors are present.

G. Belcaro, PhD, M.R. Cesarone, MD, A.N. Nicolaides, MS, A Ricci, MD, G. Geroulakos, PhD, S.S.G. Shah, MD, E. Ippolito, MD, K.A. Myers, MS, P. Bavera, MD, M Dugall, MD, M. Moia, MD, A. Di Renzo, MD, B.M. Errichi, MD, R. Brandolini, MD, M. Dugall, MD, M. Griffin, PhD, I. Ruffini, MD, A. Ricci, MD, and G. Acerbi, MD – PREVENTION OF VENOUS THROMBOSIS WITH ELASTIC STOCKINGS DURING LONG-HAUL FLIGHTS: THE LONFLIT 5 JAP STUDY, Clin Appl Thrombosis/Hemostasis 9 (3): 197-201, 2003

The aim of this study was to evaluate deep venous thrombosis (DVT) prophylaxis with specific elastic stockings in long-haul flights (11-13 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treatments; 224 were randomized into two groups (stockings vs. controls) to evaluate prophylaxis with below-knee stockings. An exercise program was used in both groups. Scholl (UK) Flight Socks (14-17 mmHg of pressure at the ankle) were used. DVT was diagnosed with ultrasound scanning. The femoral, popliteal, and tibial veins were scanned before and within 90 minutes after the flights. Of the 205 includes subjects, 102 controls and 103 treated subjects completed the study. Drop-outs were due to flight connection problems. Age, gender, and risk distributions were comparable in the two groups. In the treatment group (103 subjects; mean age, 42; SD 9; M:F, 55:48), one limited, distal DVT was observed (0.97%). In the control group (102 subjects; mean age, 42.1; SD 10.3; M:F, 56:46), six subjects (5.8%) had a DVT. There were no superficial thromboses. The difference in DVT incidence is significant (p<0.0025; six times greater in the control group). Intention-to-treat analysis counts 18 failures in the control group (12 lost to follow-up + six thromboses) of 112 subjects (15.8%) versus eight failures (7.3%) in the treatment group (p<0.05). The tolerability of the stockings was very good and there were no complaints or side effects. All events were asymptomatic. Considering these observations, Scholl Flight Socks are effective in reducing the incidence of DVT in high-risk subjects.

M. R. Cesarone, MD, G Belcaro, PhD, A.N. Nicolaides, MS, A. Ricci, MD, G. Geroulakos, PhD, E. Ippolito, MD, R. Brandolini MD, G. Vinciguerra, PhD, M. Dugall, MD M. Griffin, PhD, I. Ruffini, MD, G. Acerbi, MD, M. Corsi, MD, N. Riordan, MS, S. Stuard, MD, P. Bavera, MD, M. Dugall, MD, A. Di Renzo, MD, J. Kenyon, MD, and B.M. Errichi, MD, Pescara, Italy and London UK, PREVENTION OF VENOUS THROMBOSIS IN LONG-HAUL FLIGHTS WITH FLITE TABS: THE LONFLIT-FLITE RANDOMIZED, CONTROLLED TRIAL Angiology Volume 54, Number 0, 2003

The aim of this study was to evaluate the development of edema, and superficial and deep vein thrombosis (DVT) prophylaxis with an oral profibrinolytic agent (Flite Tabs, 150 mg pinokinase, Aidan, Tempe, AZ, USA) in long-haul flights (7-8 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treatments; 204 were randomized into 2 groups (active treatment or placebo) to evaluate the effects of propylaxis with Flite Tabs. An exercise program was used in both groups. The femoral, popliteal, tibial, and superficial veins were scanned with ultrasound before and within 90 minutes after flights. Of the included subjects, 92 or 103 controls and 94 of 101 treated subjects completed the study. Dropouts were due to connection problems. Age, gender and risk distribution were comparable in the groups. In the treatment group, no DVT was observed. In the control group, 5 subjects (5.4%) had a DVT and there were 2 superficial thromboses (7 events in 92 subjects; 7.6%). At inclusion, edema was comparable in the 2 groups. After flights there was an increase in score in controls (+12%) in comparison with a decrease (-15%) in the Flite Tabs group (the difference in variation was statistically significant). Intention-to-treat analysis for thrombotic events shows 18 failures in controls (11 lost to follow-up + 7 thrombotic events) of 92 subjects (19.6%) in comparison with 7 failures (of 94 subjects, equivalent to 7.4%) in the treatment group (p<0.05). Events were asymptomatic. In conclusion, Flite Tabs were effective in reducing thrombotic events and in controlling edema in high-risk subjects in long flights.

Paul M Ridker, M.D., Samuel Z. Goldhaber, M.D., Ellie Danielson, M.I.A.., Yves Rosenberg, M.D., Charles S. Eby, M.D., Steven R. Deitcher, M.D., Mary Cushman, M.D., Stephan Moll, M.D., Craig M. Kessler, M.D., C. Gregory Elliott, M.D., Rolf Paulson, M.D., Turnly Wong, M.D., Kenneth A. Bauer, M.D., Bruce A. Schwartz, M.D, Joseph P. Miletich, M.D., Henri Bounameaux, M.D., and Robert J. Glynn, Sc.D., for the PREVENT Investigators – LONG-TERM, LOW-INTENSITY WARFARIN THERAPY FOR THE PREVENTION OF RECURRENT VENOUS THROMBOEMBOLISM N Eng J Med 3448;15, April 10, 2003

Background: Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio. Methods. Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death Results. The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person years), a risk reduction of 64 percent (hazard ratio, 0.36 (95 percent confidence interval, 0.19 to 0.67); P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent.

F. Lapostolle, MD; S.W. Borron, MD, MS; V. Surget, MD; D. Sordelet, MD; C. Lapandry, MD; and F. Adnet, MD, PhD – STROKE ASSOCIATED WITH PULMONARY EMBOLISM AFTER AIR TRAVEL, NEUROLOGY 60, June 2003

Prolonged air travel is associated with an increased incidence of thromboembolic events. The occurrence of stroke was studied in patients with pulmonary embolism after air travel in a review of all flights arriving at Charles de Gaulle Airport in Paris during an 8-year period. Thromboembolic stroke and patent foramen ovale were diagnosed in four patients with pulmonary embolus.
Thromboembolic events, such as pulmonary embolism and deep venous thrombosis, have been increasingly recognized as complications of air travel, particularly travel of long duration. Other Thromboembolic events related to prolonged air travel are less well documented. Neurologic deficit and impairment of consciousness are unusual clinical presentations of patients with pulmonary embolism. We undertook a descriptive study of patients with this clinical presentation.
Methods. We previously studied passengers arriving at Charles de Gaulle Airport in Paris with pulmonary embolism following air travel during the period 1993 to 2000. In this study, patients with suspected pulmonary embolism requiring care and transport to hospital by French medical transport teams (SAMU) were systematically reviewed. Consecutive patients, admitted to 18 different hospitals, were included upon confirmation of the diagnosis of pulmonary embolism diagnosis by scintigrahic-ventilation perfusion scanning, angiography, or high-resolution helical CT angiography. Using the same methods, we extended the study period to include 2001. During the 8-year study period, 155 million passengers landed at Roissy Charles de Gaulle Airport. Among 65 patients with pulmonary embolus transported by SAMU after air travel, four cases of cerebrovascular accidents were observed. Stroke was diagnosed as focal neurologic deficit(s) associated with acute ischemic infarct on CT scan. The medical records of these four patients were specifically reviewed in order to describe their clinical presentation.

Barry F Jacobson, Marion Münster, Alberto Smith, Kevin G Burnand, Andrew Carter, A Talib O Abdool-Carrim, Elizabeth Marcos, Piet J Becker, Timothy Rogers, Dirk le Roux, Jennifer L Calvert-Evers, Marietha J Nel, Robyn Brackin, Martin Veller – THE BEST STUDY – A PROSPECTIVE STUDY TO COMPARE BUSINESS CLASS VERSUS ECONOMY CLASS AIR TRAVEL AS A CAUSE OF THROMBOSIS July 2003, Vol. 93, No. 7 SAMJ

As many as 10% of airline passengers travelling without prophylaxis for long distances may develop a venous thrombosis. There is, however, no evidence that economy class travellers are at increased risk of thrombosis. Objectives: A suitably powered prospective study, based on the incidence of deep-vein thrombosis (DVT) reported in previous studies on long-haul flights, was designed to determine the incidence of positive venous duplex scans and D-dimer elevations in low and intermediate-risk passengers, comparing passengers traveling in business and economy class. Patients/methods. Eight hundred and ninety-nine passengers were recruited (180 travelling business class and 719 travelling economy). D-dimers were measured before and after the flight. A value greater than 500 ng/ml was accepted as abnormal. A thrombophilia screen was conducted which included the factor V Leiden mutation, the prothrombin 20210A mutation, protein C and S levels, antithrombin levels, and anticardiolipin antibodies immunoglobulin G (lgG) and immunoglobulin M (IgM). On arrival, lower limb compression ultrasonography of the deep veins was performed. Logistical regression analysis was used to determine the risk factors related to abnormality high D-dimer levels. Results: Only 434 subjects had a full venous duplex scan performed. None had ultrasonic evidence of venous thrombosis. Nine passengers tested at departure had elevated D-dimer levels and those volunteers were excluded from further study. Seventy-four of 899 passengers had raised D-dimers on arrival. Twenty-two of 180 business class passengers (12%) developed elevated D-dimers compared with 52 of 719 economy class passengers (7%). There was no significant association between elevation of D-dimers and the class flown (odds ratio (OR) 0.61, p = 0.109). The factor V Leiden mutation, factor VIII levels and the use of aspirin were, however, associated with raised D-dimers (OR 3.36, p = 0.024; OR 1.01, p = 0.014; and OR 2.04, p = 0.038 respectively). Five hundred and five passengers were contacted within 6 months and none reported any symptoms of a clinical thrombosis or pulmonary embolus. Conclusion: The incidence of ultrasonically proven DVT is much lower than previously reported. However, more than 10% of all passengers developed raised D-dimers, which were unrelated to the class flown. A rise in D-dimers is associated with an inherent risk of thrombosis and/or thrombophilia, demonstrates activation of both the coagulation and fibrinolytic systems during long-haul flights, and may indicate the development of small thrombi.

Fabrice Paganin, Arnaud Bourdé, Jean-Luc Yvin, Robert Génin, Jean-Louis Guijarro, Arnaud Bourdin, and Christian Lassalle – VENOUS THROMBOEMBOLISM IN PASSENGERS FOLLOWING A 12-H FLIGHT: A CASE-CONTROL STUDY, Aviation Space and Environmental Medicine, Vol 74, No. 12 December 2003

There has recently been great interest in the possible relationship between air travel and venous thromboembolism (VTE). Based on a case-control survey, we measured the frequency of VTE, associated risk factors (RFs), and factors influencing the onset of pulmonary embolism (PE) or deep vein thrombosis (DVT).

The study was conducted over 1 yr. A questionnaire was sent to physicians. Patients with a diagnosis of VTE were included, provided they had traveled from France to Reunion Island.

Over 46 cases, 33 patients showed DVT and 13 PE. RFs for VTE were present in 38 patients (82%). On comparing RFs between study and control groups, we found no differences in age, gender, alcohol, sleep-inducing drug consumption, seat allocation, or estroprogestative treatment. RFs were significantly higher in the VTE group at p < 0.005: history of previous VTE (OR 63.3), recent trauma (OR 13.6), presence of varicose veins (OR 10), obesity (OR 9.6), immobility during flight (9.3), and cardiac disease (OR 8.9). For patients with DVT or PE, no differences were observed in comparing RFs. The PE group was older and mortality occurred only in this group. The number of displacements during flight (p < 0.009) and complete immobility (p < 0.001) were strongly related with onset of PE. Delay of symptoms was less than 24 h in 69% of PE cases compared with 21% of DVT cases (p < 0.004).

Long-duration air travel VTE is associated with other underlying thromboembolic RFs. Low mobility during flight is a striking modifiable RF of developing PE. Travellers with RFs for VTE should be advised to increase their mobility.

R J Hughes, R J Hopkins, S Hill, M Weatherall, N Van de Water, M Nowitz, D Milne, J Ayling, M Wilsher, R Beasley – FREQUENCY OF VENOUS THROMBOEMBOLISM IN LOW TO MODERATE RISK LONG DISTANCE AIR TRAVELLERS; THE NEW ZEALAND AIR TRAVELLER’S THROMBOSIS (NZATT) STUDY – The Lancet, Vol 362, December 20/27, 2003

Background: The frequency and role of risk factors for venous thromboembolism related to air travel is uncertain. We aimed to establish the frequency of this disorder in a group of long distance air travellers and to investigate the role of potential risk factors. Methods: We designed a prospective study into which we recruited individuals aged between 18 and 70 years, traveling for 4 h or more by aircraft. D-dimer measurement was done before and after travel. Participants with a negative D-dimer (<500 ng/L) before travel were included in the study. Those who became D-dimer positive or developed high clinical probability symptoms during the 3 months after travel were investigated with bilateral compression ultrasonography and CT pulmonary angiography. Suspected clinical and thrombophilic risk factors, and use of prophylactic measures, were assessed. Findings: 1000 individuals were recruited, with 878 meeting inclusion criteria and completing the study. All participants traveled at least 10 h, with a mean total duration of air travel of 38 h (SD 12.5). 112 patients underwent radiological assessment on return. Frequency of venous thromboembolism associated with travel was 1.0% (9/878, 95% CI 0.5-1.9), which included four cases of pulmonary embolism and five of deep vein thrombosis. Six patients with venous thromboembolism had pre-existing clinical risk factors, two had a recognised thrombophilic risk factor, two traveled exclusively in business class, five used aspirin, and four wore compression stockings. Interpretation: Our results suggest an association between multiple long distance air flights and venous thromboembolism, even in individuals at low to moderate risk. The role of traditional risk factors and prophylactic measures in air travel-related venous thromboembolism needs further investigation.

Samuel Z. Goldhaber, MD, and Victor F. Tapson, MD, for the DVT FREE Steering Committee. A PROSPECTIVE REGISTRY OF 5,451 PATIENTS WITH ULTRASOUND-CONFIRMED DEEP VEIN THROMBOSIS, The American Journal of Cardiology Vol. 93 January 15, 2004

We enrolled 5,451 patients with ultrasound-confirmed deep vein thrombosis (DVT), including 2,892 women and 2,559 men, from 183 United State sites in our prospective registry. The 5 most frequent co-morbidities were hypertension (50%), surgery within 3 months (38%), immobility within 30 days (34%), cancer (32%), and obesity (27%). Of the 2,726 patients who had their DVT diagnosed while in the hospital, only 1,147 (42%) received prophylaxis within 30 days before diagnosis.

Samuel Z Goldhaber, PULMONARY EMBOLISM, The Lancet, Vol 363, April 17, 2004

Pulmonary embolism (PE) is a common illness that can cause death and disability. It is difficult to detect because patients present with a wide array of symptoms and signs. The clinical setting can raise suspicion, and certain inherited and acquired risk factors predispose susceptible individuals. D-dimer concentration in blood is the best laboratory screening test, and chest CT has become the most widespread imaging test. Treatment requires rapid and accurate risk stratification before haemodynamic decompensation and the development of cardiogenic shock. Anticoagulation is the foundation of therapy. Right-ventricular dysfunction on echocardiography and higher than normal concentrations of troponin identify high-risk patients who might need escalation of therapy with thrombolysis or embolectomy even if the blood pressure is normal on presentation. When patients are admitted to medical wards or when patients undergo surgery, their physicians should prescribe prophylactic measures to prevent PE. After hospital discharge, prophylaxis should continue for about a month for patients at high risk of thromboembolism

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