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Exaggerated incidence of thromboembolism - ? misprint
- Mo M Mansour (7 November 2003)
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What is a long haul flight?
- Andrew Brooke (9 November 2003)
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Sex ratio not given
- Ellen Grant (9 November 2003)
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DVT and air travel
- manan vasenwala (9 November 2003)
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ADVICE TO PATIENTS: STOCKINGS, ASPIRIN OR LOW MOLECULAR WEIGHT HEPARIN?
- Y. C. Chan (15 November 2003)
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"What is already known on this topic" is incorrectly stated
- Dr Y Adi (1 December 2003)
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Interpretation of case-crossover findings
- Johanna G. van der Bom (5 December 2003)
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Underascertainment of pulmonary embolism deaths
- Derek FH Pheby, Ben W Codling (11 December 2003)
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Mo M Mansour, Consultant Gynaecologist Hexham General Hoapital. NE46 1QJ
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The introduction of the article states that "The incidence of venous thromboembolism ranges from 1000-2000 per million person years for deep vein thrombosis and 500-1000 per million person years for pulmonary embolism". The usual quoted incidence for venous thromboembolism is 5-10 per 100,000 i.e. 50-100 per million. The incidence quoted in this article is 10 fold higher - a possible misprint? Competing interests: None declared |
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Andrew Brooke, General Practitioner Gloucester. GL2 0PJ
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Would this interesting article on DVTs (Deep Vein Thrombosis) and air travel have been more informative if "long haul air travel" had been defined? How long is long haul? No-where is it specified in hours or distance exactly what long haul flight is. International air travel may mean different things to readers in different parts of the world. Travellers and clinicians may have found a clear definition useful. Competing interests: None declared |
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Ellen Grant, Physician and medical gynaecologist 20 Coombe Ridings, Kingston-upon-Thames, Surrey, KT2 7JU
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The authors have missed an opportunity to show the increased risk of thrombosis due to using progestogens and oestrogens as oral contraceptives or as hormone replacement therapy(HRT). They found more cases of thrombosis in the age groups 50-59 than in the age group 60-64. Was this because of a predominance of women takin HRT among the 50 year-olds? Competing interests: None declared |
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manan vasenwala, consultant-cardiologist(non-invasive) k.k.heart center, aligarh-202002.india
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as air travel increases, especially long haul ones, the incidence of DVT is likely to increase. the article has given data which may or may not be representative. the fact remains, from experience that actually there is stagnation of venous pool and inactivity of 'peripheral pump' during these flights. what can be done to minimise dvt arising therefrom. the following are some suggestions: 1. walk to the loo and back frequently. 2. keep on squirming your toes and do self-physiotheraphy. 3. drink plenty of fluids and avoid dehydration, 4. remove your shoes and stockings, and loosen your belt. 5. practise deep abdominal breathing. 6. take aspirin 325mg( or less) 3 days prior to journey and continue for two weeks after the journey. this is provided there is no hypersensitivity or contraindication to it like peptic ulcer or other bleeding diathesis. the above do-it-yourself may be especially useful for passengers with high risk of dvt development. Competing interests: None declared |
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Y. C. Chan, Vascular Surgical SpR University Hospital Lewisham, Lewisham High Street, London SE13 6LH.
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We are grateful to Kelman et al. for alerting us to the dangers of DVT in long-haul flights (1). More than two years ago, the initial LONFLIT Studies have already established that in high-risk subjects after long (> 10 hours) flights the incidence of DVT may be between 4% and 6% (2), whilst asymptomatic DVT might occur in up to 10% of long-haul airline travellers (3). The recent BEST Study demonstrated that more than 10% of all passengers developed raised D-dimers. This is associated with an inherent risk of thrombosis or thrombophilia, with activation of both the coagulation and fibrinolytic systems, and may indicate the development of small thrombi during long-haul flights (4). Contrary to common believe, there was no significant association between elevation of D-dimers and the class flown, either business or economy (4), and up to 85% of DVTs were observed in passengers in non-aisle seats (5). Mechanisms for the development of DVT include hypobaric hypoxia in the air cabin, blood flow stasis, dehydration through heavy alcohol consumption, and hypercoagulability. We as medical practitioners need to be familiar with the current literature, so that appropriated advice can be given to our patients. The risk of DVT can be lowered by lower limbs exercising during the flight and maintaning hydration through liberal intake of non-alcoholic beverages. Both the LONFLIT4-Concorde Deep Venous Thrombosis and Edema Study (6) and the LONFLIT 5 JAP Study (7) showed that stockings which provide pressure ranging from 14-30 mm Hg at the ankle were effective in controlling oedema and preventing micro-angiopathy during flights and were well tolerated in normal subjects and in high-risk patients. Whilst aspirin (400mg orally of soluble aspirin; one dose daily for 3 days, starting 12 hours before the beginning of the flight) did prevent DVT, more than 10% of patients reported gastrointestinal symptoms in the LONFLIT3 Study (5). Low-molecular-weight heparin (e.g.: one dose of enoxaparine injected between 2 and 4 hours before the flight), was one of the most important option to consider in high-risk subjects during long- haul flights (5). The LONFLIT4-Venoruton Study showed that hydroxy- ethylrutosides (such as venoruton) were effective in preventing DVTs in patients with established venous disease travelling in economy class (8). Most recently, the LONFLIT-FLITE Study showed that an oral profibrinolytic agent (Flite, 150 mg pinokinase- as yet unavailable in the UK), which is more easily administratable that enoxaparine, was also effective in reducing thrombotic events and in controlling oedema in high-risk subjects in long flights (9). Such is the high profile importance of the subject, both in the medical world and in the media, that we as a profession should soon draw up guidelines in DVT prophylaxis in long-haul flight passengers. References: 1. Kelman CW, Kortt MA, Becker NG, Li Z, Mathews JD, Guest CS, Holman CD. Deep vein thrombosis and air travel: record linkage study. BMJ. 2003 Nov 8; 327(7423):1072-1075. 2. Belcaro G, Geroulakos G, Nicolaides AN, Myers KA, Winford M.Venous thromboembolism from air travel: the LONFLIT study. Angiology. 2001 Jun; 52(6): 369-374. 3. Scurr JH, Machin SJ, Bailey-King S, Mackie IJ, McDonald S, Smith PD. Frequency and prevention of symptomless deep-vein thrombosis in long- haul flights: a randomised trial. Lancet. 2001 May 12; 357(9267): 1485- 1489. 4. Jacobson BF, Munster M, Smith A, Burnand KG, Carter A, Abdool- Carrim AT, Marcos E, Becker PJ, Rogers T, le Roux D, Calvert-Evers JL, Nel MJ, Brackin R, Veller M. The BEST study--a prospective study to compare business class versus economy class air travel as a cause of thrombosis. S Afr Med J. 2003 Jul; 93(7): 522-528. 5. Cesarone MR, Belcaro G, Nicolaides AN, Incandela L, De S, Geroulakos G, Lennox A, Myers KA, Moia M, Ippolito E, Winford M. 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. 2002 Jan-Feb; 53(1): 1-6. 6. Cesarone MR, Belcaro G, Errichi BM, Nicolaides AN, Geroulakos G, Ippolito E, Winford M, Lennox A, Pellegrini L, Myers KA, Ricci A, Hans C, Simeone E, Bavera P, Dugall M, Moia M, Stuard S. The LONFLIT4--Concorde Deep Venous Thrombosis and Edema Study: prevention with travel stockings. Angiology. 2003 Mar-Apr; 54(2): 143-154. 7. Belcaro G, Cesarone MR, Nicolaides AN, Ricci A, Geroulakos G, Shah SS, Ippolito E, Myers KA, Bavera P, Dugall M, Moia M, Di Renzo A, Errichi BM, Brandolini R, Dugall M, Griffin M, Ruffini I, Ricci A, Acerbi G.Prevention of venous thrombosis with elastic stockings during long-haul flights: the LONFLIT 5 JAP study. Clin Appl Thromb Hemost. 2003 Jul; 9(3): 197-201. 8. Cesarone MR, Belcaro G, Brandolini R, Di Renzo A, Bavera P, Dugall M, Simeone E, Acerbi G, Ippolito E, Winford M, Candiani C, Golden G, Ricci A, Stuard S. The LONFLIT4-Venoruton Study: a randomized trial--prophylaxis of flight-edema in venous patients. Angiology. 2003 Mar-Apr; 54(2): 137- 142. 9. Cesarone MR, Belcaro G, Nicolaides AN, Ricci A, Geroulakos G, Ippolito E, Brandolini R, Vinciguerra G, Dugall M, Griffin M, Ruffini I, Acerbi G, Corsi M, Riordan NH, Stuard S, Bavera P, Di Renzo A, Kenyon J, Errichi BM. Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial. Angiology. 2003 Sep-Oct; 54(5): 531-539. Competing interests: None declared |
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Dr Y Adi, Systematic Reviewer Department of Public Health & Epidemiology, University of Birmingham, B15 2TT
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In their interesting paper, Kelman et al (1) stated that: "Venous thromboembolism has been suggested to be up to four times more likely to develop within two to four weeks of a flight". This statement is not supported by any evidence and is in fact misleading. The only reference in the literature to quote the risk as high as four was of Ferrari et al (2) and this reference of high risk of DVT in air travel was quoted by Kelman et al(1)in their introduction section. Ferrari et al (2) stated the odds ratio of 3.98, 95% CI (1.9-8.4) for the increased risk of DVT in relation to ANY TRAVEL in their case control study. There were 39/160 of DVT in relation to any travel and 12/160 in the control group. All journeys undertaken during the preceding 4 weeks and lasting > 4 hours by whatever means of transport were considered and not two to four weeks of a history of flight as it was stated by Kelman et al (1). In fact out of the 39 cases of DVT in relation to travel, there were 2 cases in which the travel was by train, 9 by airplane 29 in cars. Furthermore, Ferrari et al (2) study used a control group of patients who were admitted to a cardiology department, and therefore the control individuals might be too ill in the last four weeks to have travelled and this was the reason that could explain the high odds ratio they reported in relation to travel. 1. Kelman CW, Kortt MA, Becker NG, Li Z, Mathews JD, Guest CS, Holman CD. Deep vein thrombosis and air travel: record linkage study. BMJ 2003;327:1072-1075. 2. Ferrari E, Chevallier T, Chapelier A, Baudouy M. Travel as a risk factor for venous thromboembolic disease: a case-control study. Chest 1999;115:440-4. Competing interests: None declared |
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Johanna G. van der Bom, Associate professor of clinical epidemiology Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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Sir,- the ingenious record linkage study by Kelman et al. [1] shows that among 153 Australian citizens who were admitted to hospital with venous thromboembolism within 100 days after a long haul flight between 1981 and 1999 the incidence rate ratio for venous thromboembolism was increased by a factor 4 during the first two weeks after this flight as compared to the period afterwards. The authors conclude that the risk for venous thromboembolism is four times increased within two weeks of arrival from a long haul flight. However, an important limitation of the case- crossover study is a limitation in the interpretation of the findings. Since this relative effect of flying was studied solely among subjects that had a venous thrombembolism, it may be suspected that, in addition to the healthy flyer effect, these results may be biased in another way. Case -crossover analyses depend on matched comparisons of current and past exposures. Such paired analyses tend to suffer more bias from misclassification than ordinary unpaired analyses.[2] At issue is whether we expect a difference in the effect of flying between subjects at increased risk for thromboembolic events and subjects at 'normal' risk of thromboembolic events. There is ample evidence that the effect of environmental risk factors on the occurrence of thromboembolic events is modified by genetic predisposition to such events. [3,4] It may thus be expected that the findings of Kelman et al only hold for subjects with an increased susceptibility to thromboembolic events and not for all subjects arriving after a long haul flight. It is important to keep in mind that the most fundamental limitation of a case-crossover study is inherent in the question it is designed to answer, "Why did these people have a thromboembolic event now rather than a month ago?".[5] If one also wants to answer the question "Why did these people have a thromboembolic events, whereas other people at the same time did not", a traditional case-control must be conducted simultaneously, or the case-crossover study must be nested in a cohort study.[5] It appears that both these type of designs and analyses could have been performed within the available data. In conclusion, since the effect of air travel on deep vein thrombosis may be modified by a genetic predispostion to deep vein thrombosis, the results of a case-crossover study on this topic should be generalized with caution. References 1) Kelman CW, Kortt MA, Becker NG, Li Z, Mathews JD, Guest CS, Holman CD. Deep vein thrombosis and air travel: record linkage study. BMJ. 2003 Nov 8;327(7423):1072-11. 2) Greenland S. The effect of misclassification in matched-pair case- control studies. Am J Epidemiol 1982;116:402-6. 3) van Boven HH, Vandenbroucke JP, Briet E, Rosendaal FR. Gene-gene and gene-environment interactions determine risk of thrombosis in families with inherited antithrombin deficiency..Blood 1999;94:2590-4. 4) Martinelli I, Taioli E, Bucciarelli P, Akhavan S, Mannucci PM. Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscler Thromb Vasc Biol. 1999;19(3):700-3. 5)Maclure M, Mittleman MA. Should we use a case-crossover design? Annu Rev Publec Health 2000;21:193-221. Competing interests: None declared |
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Derek FH Pheby, Director, Unit of Applied Epidemiology University of the West of England, Bristol, Ben W Codling
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Kelman et al (1) have performed a useful service in getting into proportion the relatively low risk of death from long-haul flight-related venous thromboembolism. They estimate that risk as being one per two million long-haul arrivals in Western Australia. Applying this proportion to the UK would suggest that, for example in 1998, when there were approximately 37.2 million long-haul arrivals in Britain (2), some 18 to 19 such deaths could be expected. This is somewhat higher than our own estimate, which was that around 6.55 deaths per annum could be expected in this group (3). This is not entirely unexpected, as we defined long-haul as all flights other than from Europe or the Maghreb region of North Africa. Long-haul flights into Western Australia are therefore likely to be longer on average than long-haul flights into the UK, and the observation period is therefore longer, and there are certainly risk factors for venous thromboembolism associated with long flights. Our concern was that the incidence of death from flight-related pulmonary embolism is frequently seen by the media and the general public as being substantially elevated in comparison with that found in the general population, because of marked under- reporting of pulmonary embolism as a cause of death. We compared death certifications in West Gloucestershire with post mortem findings. The average mortality rate from pulmonary embolism in 1996-2000, as ascertained from death certificates, was 7.84 per 100,000 population. However, the results of post mortems indicated that the true figure was more in the region of 89.9 deaths per 100,000 population, and that therefore some death certificates are failing to report the true cause of death in more than 91% of deaths associated with pulmonary embolism. When this underreporting is taken into account, the relative risk of death from pulmonary embolism due to long-haul flight is markedly reduced. This finding of underascertainment of pulmonary embolism as a cause of death is consistent with other work in this area, including in Australia. Thus, a review by McKelvie of accuracy of death certification in an Australian metropolitan hospital in 1993 found that the rate of clinical diagnostic inaccuracy for major findings at autopsy was about a third. This rate had not changed since 1912 (4). Similarly, the results of a recent study were presented, in late 2002, at the annual conference in America of National Association of Medical Examiners (NAME) (5). This report reviewed certificated cause of death in 261 cases from the Sydney area. Comparison with autopsy data indicated that 28% of registered causes of death were incorrect, while a further 46% were only partially correct. 1) C W Kelman, M A Kortt, N G Becker, et al. Deep vein thrombosis and air travel: record linkage study. BMJ 2003; 327:1072-5. 2) Passengers at Gatwick, Heathrow and Manchester Airports in 1998. CAP 703. London, Civil Aviation Authority, 1999. 3) Pheby DFH, Codling BW. Pulmonary embolism at autopsy in a normal population: implications for air travel fatalities. Aviat Space Environ Med 2002; 73:1208 –14. 4) McKelvie PA. Medical certification of causes of death in an Australian metropolitan hospital. Comparison with autopsy findings and a critical review. Med J Aust 1993; 158: 816-821 5) Nashelsky MB, Lawrence CH. Accuracy of cause of death determination without forensic autopsy examination. National Association of Medical Examiners Conference, October 2002. Competing interests: None declared |
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